OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells wer...OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells were treated with CTX[0(cell control),0.01,0.1,1,5,10,20,40 and 80 mmol·L^(-1)]and 4-HC[0(cell control),0.01,0.1,1,5,10,20,40 and 80μmol·L^(-1)]for 48 h.Cell confluence and morphology were observed by the IncuCyte ZOOM system.Cell viability was assessed by CCK-8 assay.Lactate dehydrogenase(LDH)release was measured by LDH assay kit.SH-SY5Y cells were treated with CTX(0,1,5,10 and 20 mmol·L^(-1))and 4-HC(0,1,5,10 and 20μmol·L^(-1))for 48 h before cell proliferation was analyzed by 5-ethynyl-2′-deoxyuridine(EdU)staining assay.Immunofluorescence was employed to assess the levels of the DNA double-strand break markerγ-H2AX and to evaluate changes in mitochondrial membrane potential.SH-SY5Y cells were treated with CTX(0,1,5 and 10 mmol·L^(-1))and 4-HC(0,1,5 and 10μmol·L^(-1))for 48 h,and the alterations in glycolysis and oxidative phosphorylation levels were analyzed using the Seahorse XFe96 Analyzer.RESULTS Compared with the cell control group,cell confluence and cell viability were significantly reduced in the CTX and 4-HC groups(P<0.01),and the half-maximal inhibitory concentrations(IC50)for CTX and 4-HC were 4.44 mmol·L^(-1) and 4.78μmol·L^(-1),respectively.The release rate of LDH was signif⁃icantly increased while the percentage of EdU+cells was significantly reduced in the CTX and 4-HC groups(P<0.01).The percentage ofγ-H2AX+cells was significantly increased and mitochondrial membrane potential significantly decreased in the CTX and 4-HC group(P<0.05).Treatment with CTX and 4-HC resulted in reduced levels of maximum glycolytic capacity,glycolytic reserve,maximal respi⁃ration,and ATP production(P<0.05).CONCLUSION CTX and 4-HC exert significant cytotoxic effects on SH-SY5Y cells by disrupting cell membrane structure,impeding cell proliferation,and reducing cell viability.The mechanisms underlying these effects may involve intracellular DNA damage,disturbance of energy metabolism and mitochondrial dysfunction.展开更多
Objective:To explore the effect of geraniol on cyclophosphamide-induced cardiotoxicity.Methods:Mice were divided into five groups:the control group,the cyclophosphamide group(200 mg/kg cyclophosphamide,i.p.on day 7),t...Objective:To explore the effect of geraniol on cyclophosphamide-induced cardiotoxicity.Methods:Mice were divided into five groups:the control group,the cyclophosphamide group(200 mg/kg cyclophosphamide,i.p.on day 7),the group treated with geraniol 100 and 200 mg/kg from day 1 to day 14,along with a single dose of cyclophosphamide on day 7,and the geraniol alone group(200 mg/kg geraniol from day 1 to day 14).At the end of the study,animals were sacrificed,and blood and heart were collected and analyzed for biochemical,histopathological,and immunohistochemical changes.Results:Treatment with 200 mg/kg geraniol significantly reduced the levels of cardiac injury markers,malondialdehyde,and inflammatory and apoptotic markers,while increasing antioxidant activities in mice with cyclophosphamide-induced cardiotoxicity.Moreover,it remarkably alleviated histopathological aberrations in cardiac tissue.Conclusions:Geraniol attenuates cyclophosphamide-induced cardiotoxicity via antioxidant,anti-inflammatory,and antiapoptotic effects.展开更多
Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenva...Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.展开更多
BACKGROUND Parthenolide(PTL),a sesquiterpene lactone derived from the medicinal herb Chrysanthemum parthenium,exhibits various biological effects by targeting NF-kB,STAT3,and other pathways.It has emerged as a promisi...BACKGROUND Parthenolide(PTL),a sesquiterpene lactone derived from the medicinal herb Chrysanthemum parthenium,exhibits various biological effects by targeting NF-kB,STAT3,and other pathways.It has emerged as a promising adjunct therapy for multiple malignancies.AIM To evaluate the in vitro and in vivo effect of PTL on cyclophosphamide(CTX)metronomic chemotherapy.METHODS The cytotoxicity of PTL and CTX on Lewis lung cancer cells(LLC cells)was assessed by measuring cell activity and apoptosis.The anti-tumor efficiency was evaluated using a tumor xenograft mice model,and the survival of mice and tumor volume were monitored.Additionally,the collected tumor tissues were analyzed for tumor microenvironment indicators and inflammatory factors.RESULTS In vitro,PTL demonstrated a synergistic effect with CTX in inhibiting the growth of LLC cells and promoting apoptosis.In vivo,metronomic chemotherapy com-bined with PTL and CTX improved the survival rate of tumor-bearing mice and reduced tumor growth rate.Furthermore,metronomic chemotherapy combined with PTL and CTX reduced NF-κB activation and improved the tumor immune microenvironment by decreasing tumor angiogenesis,reducing Transforming growth factorβ,andα-SMA positive cells.CONCLUSION PTL is an efficient compound that enhances the metronomic chemotherapy effects of CTX both in vitro and in vivo,suggesting its potential as a supplementary therapeutic strategy in metronomic chemotherapy to improve the chemotherapy effects.展开更多
目的探讨β胶原特殊序列(β-crosslaps,β-CTX)、总1型胶原氨基端延长肽(t-P1NP)及N端中段骨钙素(N-MID-OT)在绝经后女性骨质疏松性骨折风险评估中的应用价值。方法回顾性分析2020年2月至2022年12月解放军总医院第六医学中心收治的102...目的探讨β胶原特殊序列(β-crosslaps,β-CTX)、总1型胶原氨基端延长肽(t-P1NP)及N端中段骨钙素(N-MID-OT)在绝经后女性骨质疏松性骨折风险评估中的应用价值。方法回顾性分析2020年2月至2022年12月解放军总医院第六医学中心收治的102例绝经后骨质疏松(postmenopausal osteoporosis,PMOP)患者的临床资料,将其作为研究组,并根据是否发生骨折将其分为PMOP骨折组(39例)与PMOP未骨折组(63例),另选100名健康体检者作为对照组。记录所有研究对象的β-CTX、t-P1NP及N-MID-OT水平并进行比较,用ROC曲线评价β-CTX、t-P1NP及N-MID-OT在绝经后女性骨质疏松性骨折风险评估中的应用价值。结果研究组的平均体重、体质量指数、股骨颈骨密度(bone mineral density,BMD)、左髋总和BMD及L 1~4总和BMD均明显低于对照组(P<0.05);而两组研究对象的平均年龄、平均身高及绝经年龄等比较差异均无统计学意义(P>0.05)。研究组的β-CTX、t-P1NP及N-MID-OT均明显高于对照组(t值依次为12.688、37.430、26.599,P<0.05)。β-CTX+t-P1NP+N-MID-OT联合检测用于预测PMOP的AUC值为0.978,敏感度为98.04%,特异度为97.00%,表明β-CTX+t-P1NP+N-MID-OT三指标联合检测用于预测PMOP的效能更高。PMOP骨折组的β-CTX、t-P1NP及N-MID-OT均明显高于PMOP未骨折组(t值依次为6.078、16.363、12.227,P<0.05)。β-CTX+t-P1NP+N-MID-OT联合检测用于评估PMOP骨折风险的AUC值为0.939,敏感度为94.87%,特异度为95.24%,表明β-CTX+t-P1NP+N-MID-OT联合检测用于评估PMOP骨折风险的效能更高。结论PMOP患者β-CTX、t-P1NP及N-MID-OT水平均明显升高,而PMOP骨折患者β-CTX、t-P1NP及N-MID-OT水平升高更为明显,且β-CTX+t-P1NP+N-MID-OT联合检测可显著提高对PMOP预测及骨折风险评估效能,值得借鉴。展开更多
The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide(MP)on cyclophosphamide(CTX)induced liver injury in mice.To explore metabolic profile of liver tissue an...The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide(MP)on cyclophosphamide(CTX)induced liver injury in mice.To explore metabolic profile of liver tissue and feces among normal group,CTX-induced group and MP management group based on metabolomics method by using UPLC-Q-TOF/MS.The results showed that MP could alleviate liver injury and promote the production of short chain fatty acids(SCFAs),with the best dose of 200 mg/kg·body weight(bw).The principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLSDA)scores plots of the liver and feces samples showed a clear separation among normal,model and highdose of MP(MPH).There were 18 endogenous metabolites in liver and 29 endogenous metabolites in feces,which were mainly involved in 8 metabolic pathways:taurine and hypotaurine metabolism,phenylalanine metabolism,α-linolenic acid metabolism,tricarboxylic acid(TCA)cycle,phenylalanine,tyrosine and tryptophan biosynthesis,arachidonic acid metabolism,sphingolipid metabolism as well as tryptophan metabolism.Moreover,a common metabolite arachidonic acid was observed in liver and feces samples.These endogenous metabolites may be considered to be MP’s response to liver protection.It will help to further understand the mechanism of MP and provide a basis for further research.展开更多
BACKGROUND Pseudomyxoma peritonei(PMP)is a rare peritoneal malignant tumor syndrome.Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is its standard treatment.However,there are few studies...BACKGROUND Pseudomyxoma peritonei(PMP)is a rare peritoneal malignant tumor syndrome.Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is its standard treatment.However,there are few studies and insufficient evidence regarding systemic chemotherapy of advanced PMP.Regimens for colorectal cancer are often used clinically,but there is no uniform standard for late-stage treatment.AIM To determine if bevacizumab combined with cyclophosphamide and oxaliplatin(Bev+CTX+OXA)is effective for treatment of advanced PMP.The primary study endpoint was progression-free survival(PFS).METHODS Retrospective analysis was conducted on the clinical data of patients with advanced PMP who received Bev+CTX+OXA regimen(bevacizumab 7.5 mg/kg ivgtt d1,oxaliplatin 130 mg/m2 ivgtt d1 and cyclophosphamide 500 mg/m2 ivgtt d1,q3w)in our center from December 2015 to December 2020.Objective response rate(ORR),disease control rate(DCR)and incidence of adverse events were evaluated.PFS was followed up.Kaplan-Meier method was used to draw survival curve,and log-rank test was used for comparison between groups.Multivariate Cox proportional hazards regression model was used to analyze the independent influencing factors of PFS.RESULTS A total of 32 patients were enrolled.After 2 cycles,the ORR and DCR were 3.1%and 93.7%,respectively.The median follow-up time was 7.5 mo.During the follow-up period,14 patients(43.8%)had disease progression,and the median PFS was 8.9 mo.Stratified analysis showed that the PFS of patients with a preoperative increase in CA125(8.9 vs 2.1,P=0.022)and a completeness of cytoreduction score of 2-3(8.9 vs 5.0,P=0.043)was significantly longer than that of the control group.Multivariate analysis showed that a preoperative increase in CA125 was an independent prognostic factor for PFS(HR=0.245,95%CI:0.066-0.904,P=0.035).CONCLUSION Our retrospective assessment confirmed that the Bev+CTX+OXA regimen is effective in second-or posterior-line treatment of advanced PMP and that adverse reactions can be tolerated.A preoperative increase in CA125 is an independent prognostic factor of PFS.展开更多
Background:To explored whether moxa cone moxibustion can reduce peritoneal inflammation by increasing the content of peritoneal macrophages and B cells via interferon-gamma.Methods:The mice were randomly divided into ...Background:To explored whether moxa cone moxibustion can reduce peritoneal inflammation by increasing the content of peritoneal macrophages and B cells via interferon-gamma.Methods:The mice were randomly divided into three groups with six mice in each group:the control group,model group,and moxibustion group,and the model was established in mice using cyclophosphamide.In the moxibustion group,the mice received moxa cone moxibustion at Zusanli(ST36)for 7 days.Analysis of Peritoneal cell were detected by flow cytometry and immunofluorescence,the protein expression level in the peritoneal fluid were measured with mouse cytokine antibody arrays and verified by enzyme linked immuno sorbent assay test,and RNA-Sequencing was used for peritoneal cell RNA analysis.Results:Our results showed that moxa cone moxibustion could reduce the loss of large peritoneal macrophages and B1 cells(P<0.05).With the cytokine array analysis and enzyme linked immuno sorbent assay test of peritoneal fluid,we found that IFN‐γwas up-regulated in moxibustion group(P<0.05).There were 169 genes were down-regulated in the model group and up-regulated in the moxibustion group while 19 genes that were up-regulated in the model group and down-regulated in the moxibustion group via RNA-sequencing.Kyoto Encyclopedia of Genes and Genomes pathway analysis of 188 intersect differentially expressed genes were found that the top 3 pathways with the highest enrichment of up-regulated genes included Hematopoietic cell lineage,Inflammatory bowel disease and Malaria.The differentially expressed genes visualization protein-protein interaction network shows the top 10 genes including Ifng,Grb2,CCR7,CTLA4,CXCR5,Foxp3,kit,PRF1,CD5 and klrg1.Conclusion:These findings showed that moxa cone moxibustion can alleviate chemotherapy-induced diarrhea by reducing the loss of large peritoneal macrophages and B1 cells in the peritoneal cavity,possibly through up-regulating inflammatory bowel disease signaling pathway via interferon-gamma to regulate the survival and function of large peritoneal macrophages and B1 cells.展开更多
Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7...Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.展开更多
An experiment was conducted to compare the effects of two mouse thrombocytopenia models induced by cyclophosphamide at two different administration routes to determine a proper cyclophosphamide administration route th...An experiment was conducted to compare the effects of two mouse thrombocytopenia models induced by cyclophosphamide at two different administration routes to determine a proper cyclophosphamide administration route that could cause stable thrombocytopenia. A suitable drug dosage that could induce thrombocytopenia in mouse efficiently with the definite administration route was then investigated. BALB/c mice were randomly divided into Normal, Model A and Model B groups. To Model A, 200 mg/kg of cyclophosphamide was given by vena caudalis injection as first dose and 30 mg/kg as maintenance dose by intraperitoneal injection at the following 6 days. To Model B, 150 mg/kg of cyclophosphamide was given by subcutaneous injection once a day for consecutive 3 days. All groups were under investigation for 15 days. The result suggested that a decrease in the number of blood platelets of Model B at the 7th day were significantly than that of Normal. Other platelet related indices like platelet distribution width, mean platelet volume and platelet-large cell ratio of Model B increased significantly in comparison with those of Normal group. The platelets count was reduced but fluctuated greatly, and more than half of the mice died in Model A. Therefore, subcutaneous injection of cyclophosphamide for 3 days was used for the cyclophosphamide dosage test. BALB/c mice were randomly divided into Normal, cyclophosphamide low dose （100 mg/kg）, medium dose （120 mg/kg） and high dose （140 mg/kg） groups. All groups were under investigation for 11 days. Though all 3 dosages successfully initiated thrombocytopenia as the platelets number dropped at the 7th day, the low dose was considered to be a suitable one that was of high efficacy and low toxicity. Thus, BALB/c mice challenged by subcutaneous injection of cyclophosphamide 100 mg/kg per day for 3 consecutive day is one simple, feasible and stable mouse thrombocytopenia model that could be used for pharmacodynamic test of the drugs which are supposed to have platelets increasing effect.展开更多
The protective effect of a kind of purified polysaccharides extracted from Radix of Phytolacca acinosa Roxb,with a molecular weight of 10 KDa,on hematopoiesis was investigated.Average survival time of mice treated wit...The protective effect of a kind of purified polysaccharides extracted from Radix of Phytolacca acinosa Roxb,with a molecular weight of 10 KDa,on hematopoiesis was investigated.Average survival time of mice treated with cyclophosphamide (CY) 300 mg/kg once alone was 13.3 ± 7.2d(n=7) however,average survival time of mice treated with CY 300 mg/kg in com-bination with PAP-1 10 mg/kg,3 times/wk was 36.7± 16.4d(n=7,P<0.01).PAP-1,ip had benefi-cial effect on the recovery of the CY induced decrease of peripheral leukocyte number,and the nu-cleated bone marrow cell(BMC)number and[3￣H]TdR uptaken by BMC induced by rmGM-CSF in S180 bearing mice treated with CY,In mice,after the first ip treatment with CY 100 mg/kg on d7,the peripheral leukocyte number decreased on d9 and recovered to normal level about d13 to d15. Such recovery was accelerated by administrating PAP-1,10mg/kg, 3 times/wk.A significant in-crease of the activity to form colony in spleen(colony-forming unit in spleen, CFU-S_8, CUF-S12) in mice irradiated with 550 rad 6O￣Co γ-rays and an enhancement of proliferative response of BMC to rmGM-CSF treated with PAP-1,10mg/kg,3 times/wk, ip were observed.After PAP-1,10 mg/kg,ip once,a significant increase in the number of peripheral blood leukocytes and a rise in the serum of colony stimulating factor(CSF) were also confirmed.The types of CSF in serum were M-CSF and other hematopoietic growth factors,which were confirmed by using McAb of IL-3, GM-CSF and PcAb of M-CSF. These beneficial effects of PAP-1 on hematopoiesis may be related to its activityinducing CSFs and other hematopoietic growth factors and warrant further evaluation of its use-fulness.展开更多
Objective:The aim of the study was to investigate the effects as well as the possible mechanisms of low dose γ-ray pre-irradiation on hepatic damage,DNA damage of peripheral lymphocytes and genetic material damage ca...Objective:The aim of the study was to investigate the effects as well as the possible mechanisms of low dose γ-ray pre-irradiation on hepatic damage,DNA damage of peripheral lymphocytes and genetic material damage caused by high dosage of cyclophosphamide(CTX).Methods:Kunming strain male mice were randomly divided into five groups:control group,sham-irradiated group,low dose irradiation group(LDR group),cyclophosphamide chemotherapy group(CTX group) and low dose irradiation combined with chemotherapy group(LDR + CTX group).Having being raised for one week,all the mice were implanted subcutaneously with S180 cells in the left inguen(control group excluded).On days 8 and 11,mice of LDR and LDR + CTX groups were given 75 mGy whole-body γ-irradiation,30 h later mice of CTX and LDR + CTX groups were injected i.p.3.0 mg cyclophosphamide.All the mice were sacrificed on day 13.DNA damage of the peripheral lymphocytes was analyzed using single cell gel electrophoresis(SCGE);ALT activity,total protein(TP) and albumin(ALB) of the plasma were analyzed using automatic biochemistry analyzer;MDA content,SOD and GSH-PX activity of the hepatic homogenate were analyzed using chromometry;genetic material damage was analyzed using micronucleus frequency(MNF) of polychromatoerythrocytes(PCE) in bone marrow.Results:1.Differences of MDA contents,SOD and GSH-PX activity of hepatic homogenate between 5 groups had notable statistical significance(P < 0.01);in control group MDA content was the lowest,SOD and GSH-PX activity were the highest,while in CTX group MDA content was the highest,SOD and GSH-PX activity were the lowest;compared with CTX group MDA content decreased significantly(P < 0.01) and SOD and GSH-PX activity increased significantly(P < 0.05) in LDR + CTX group.2.Differences of ALT activity of plasma between 5 groups had no statistical significance(F = 1.262,P > 0.05).Differences of TP and ALB of plasma between 5 groups had statistical significance(F = 12.879 and 6.336 respectively,P < 0.01);TP and ALB in control group were higher than those of other groups and compared with sham-irradiated group,TP and ALB in LDR group elevated significantly(P < 0.05).3.Differences of DNA damage of peripheral lymphocytes had notable statistical significance(F = 6.383,P < 0.01);DNA damage in control group was the lightest,while DNA damage in CTX group was the severest;compared with CTX group,DNA damage in LDR + CTX group was much lighter(P < 0.05).4.MNF of PCE between 5 groups had remarkable significance(F = 179.652,P < 0.01);compared with control group and sham-irradiated group,MNF in CTX group increased significantly(P < 0.01);compared with CTX group,MNF in LDR + CTX group had a tendency of decline,which had no statistical significance(P > 0.05).Conclusion:1.CTX can damage the hepatic tissue through oxidative stress;75 mGy γ-irradiation before CTX chemotherapy can induce activities of anti-oxidative enzymes,promote elimination of free radicals,so as to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-dose chemotherapy.2.A 75 mGy γ-irradiation before CTX chemotherapy has no obvious effect on ALT activity of plasma,but may have protective effect on the protein synthesis function of liver.3.High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes;75 mGy γ-irradiation before chemotherapy may have certain protective effect on DNA damage.4.CTX has potent mutagenic effect,can cause significant increase of MNF of PCE;75 mGy γ-ray pre-irradiation did not show obvious protection against genetic toxicity of high-dose CTX chemotherapy.展开更多
Aim:To study the detrimental effects of cyclophosphamide on the testicular androgenic and gametogenic activities through endocrine inhibition and/or induction of oxidative stress in male albino rats and to evaluate th...Aim:To study the detrimental effects of cyclophosphamide on the testicular androgenic and gametogenic activities through endocrine inhibition and/or induction of oxidative stress in male albino rats and to evaluate the protective effect of ascorbic acid.Methods:The testicular△^(5),3β-hydroxysteroid dehydrogenase(HSD),17β-HSD,peroxidase and catalase activities along with the levels of malondialdehyde(MDA)and conjugated dienes in testicular tissue were measured for the evaluation of testicular oxidative stress.The plasma testosterone(T)level was measured by immunoassay.Various germ cells at stageⅦof spermatogenic cycle were quantified from testicular stained sections.Results:Cyclophosphamide treatment results in a significant inhibition in the testicular△^(5),3β-HSD and 17β-HSD activities,a decrease in plasma T level and a diminution in the counts of various germ cells.Moreover,this treatment was also associated with a significant inhibition of the peroxidase and catalase activities along with high levels of MDA and conjugated dienes in the testis.All these changes were reversed by ascorbic acid co-administration.Conclusion:Cyclophosphamide treatment at the dosage used caused testicular gametogenic and androgenic disorders as well as induced testicular oxidative stress that can be reversed by ascorbic acid co-administration.展开更多
文摘OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells were treated with CTX[0(cell control),0.01,0.1,1,5,10,20,40 and 80 mmol·L^(-1)]and 4-HC[0(cell control),0.01,0.1,1,5,10,20,40 and 80μmol·L^(-1)]for 48 h.Cell confluence and morphology were observed by the IncuCyte ZOOM system.Cell viability was assessed by CCK-8 assay.Lactate dehydrogenase(LDH)release was measured by LDH assay kit.SH-SY5Y cells were treated with CTX(0,1,5,10 and 20 mmol·L^(-1))and 4-HC(0,1,5,10 and 20μmol·L^(-1))for 48 h before cell proliferation was analyzed by 5-ethynyl-2′-deoxyuridine(EdU)staining assay.Immunofluorescence was employed to assess the levels of the DNA double-strand break markerγ-H2AX and to evaluate changes in mitochondrial membrane potential.SH-SY5Y cells were treated with CTX(0,1,5 and 10 mmol·L^(-1))and 4-HC(0,1,5 and 10μmol·L^(-1))for 48 h,and the alterations in glycolysis and oxidative phosphorylation levels were analyzed using the Seahorse XFe96 Analyzer.RESULTS Compared with the cell control group,cell confluence and cell viability were significantly reduced in the CTX and 4-HC groups(P<0.01),and the half-maximal inhibitory concentrations(IC50)for CTX and 4-HC were 4.44 mmol·L^(-1) and 4.78μmol·L^(-1),respectively.The release rate of LDH was signif⁃icantly increased while the percentage of EdU+cells was significantly reduced in the CTX and 4-HC groups(P<0.01).The percentage ofγ-H2AX+cells was significantly increased and mitochondrial membrane potential significantly decreased in the CTX and 4-HC group(P<0.05).Treatment with CTX and 4-HC resulted in reduced levels of maximum glycolytic capacity,glycolytic reserve,maximal respi⁃ration,and ATP production(P<0.05).CONCLUSION CTX and 4-HC exert significant cytotoxic effects on SH-SY5Y cells by disrupting cell membrane structure,impeding cell proliferation,and reducing cell viability.The mechanisms underlying these effects may involve intracellular DNA damage,disturbance of energy metabolism and mitochondrial dysfunction.
基金The Deanship of Scientific Research at King Abdulaziz University,Jeddah,Saudi Arabia has funded this project under grant no.RG-21-166-43.
文摘Objective:To explore the effect of geraniol on cyclophosphamide-induced cardiotoxicity.Methods:Mice were divided into five groups:the control group,the cyclophosphamide group(200 mg/kg cyclophosphamide,i.p.on day 7),the group treated with geraniol 100 and 200 mg/kg from day 1 to day 14,along with a single dose of cyclophosphamide on day 7,and the geraniol alone group(200 mg/kg geraniol from day 1 to day 14).At the end of the study,animals were sacrificed,and blood and heart were collected and analyzed for biochemical,histopathological,and immunohistochemical changes.Results:Treatment with 200 mg/kg geraniol significantly reduced the levels of cardiac injury markers,malondialdehyde,and inflammatory and apoptotic markers,while increasing antioxidant activities in mice with cyclophosphamide-induced cardiotoxicity.Moreover,it remarkably alleviated histopathological aberrations in cardiac tissue.Conclusions:Geraniol attenuates cyclophosphamide-induced cardiotoxicity via antioxidant,anti-inflammatory,and antiapoptotic effects.
基金financially supported by the Science and Technology Plan Project of Guangzhou (No. 202102010171)National Natural Science Foundation Cultivation Project of the Third Affiliated Hospital of Sun Yat-sen University (No. 2020GZRPYMS11)+2 种基金Natural Science Foundation of Guangdong Province (No. 2018A030313641)Natural Science Foundation of Guangdong Province (No. 2016A030313848)Science and Technology Plan Project of Guangzhou (No. 201704020175)。
文摘Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.
基金Supported by Joint Funding of Yunnan Ministry of Science and Technology,No.2019FF002-048and Beijing Heathco Clinical Oncology Research Foundation,No.Y-Q201802-048.
文摘BACKGROUND Parthenolide(PTL),a sesquiterpene lactone derived from the medicinal herb Chrysanthemum parthenium,exhibits various biological effects by targeting NF-kB,STAT3,and other pathways.It has emerged as a promising adjunct therapy for multiple malignancies.AIM To evaluate the in vitro and in vivo effect of PTL on cyclophosphamide(CTX)metronomic chemotherapy.METHODS The cytotoxicity of PTL and CTX on Lewis lung cancer cells(LLC cells)was assessed by measuring cell activity and apoptosis.The anti-tumor efficiency was evaluated using a tumor xenograft mice model,and the survival of mice and tumor volume were monitored.Additionally,the collected tumor tissues were analyzed for tumor microenvironment indicators and inflammatory factors.RESULTS In vitro,PTL demonstrated a synergistic effect with CTX in inhibiting the growth of LLC cells and promoting apoptosis.In vivo,metronomic chemotherapy com-bined with PTL and CTX improved the survival rate of tumor-bearing mice and reduced tumor growth rate.Furthermore,metronomic chemotherapy combined with PTL and CTX reduced NF-κB activation and improved the tumor immune microenvironment by decreasing tumor angiogenesis,reducing Transforming growth factorβ,andα-SMA positive cells.CONCLUSION PTL is an efficient compound that enhances the metronomic chemotherapy effects of CTX both in vitro and in vivo,suggesting its potential as a supplementary therapeutic strategy in metronomic chemotherapy to improve the chemotherapy effects.
文摘目的探讨β胶原特殊序列(β-crosslaps,β-CTX)、总1型胶原氨基端延长肽(t-P1NP)及N端中段骨钙素(N-MID-OT)在绝经后女性骨质疏松性骨折风险评估中的应用价值。方法回顾性分析2020年2月至2022年12月解放军总医院第六医学中心收治的102例绝经后骨质疏松(postmenopausal osteoporosis,PMOP)患者的临床资料,将其作为研究组,并根据是否发生骨折将其分为PMOP骨折组(39例)与PMOP未骨折组(63例),另选100名健康体检者作为对照组。记录所有研究对象的β-CTX、t-P1NP及N-MID-OT水平并进行比较,用ROC曲线评价β-CTX、t-P1NP及N-MID-OT在绝经后女性骨质疏松性骨折风险评估中的应用价值。结果研究组的平均体重、体质量指数、股骨颈骨密度(bone mineral density,BMD)、左髋总和BMD及L 1~4总和BMD均明显低于对照组(P<0.05);而两组研究对象的平均年龄、平均身高及绝经年龄等比较差异均无统计学意义(P>0.05)。研究组的β-CTX、t-P1NP及N-MID-OT均明显高于对照组(t值依次为12.688、37.430、26.599,P<0.05)。β-CTX+t-P1NP+N-MID-OT联合检测用于预测PMOP的AUC值为0.978,敏感度为98.04%,特异度为97.00%,表明β-CTX+t-P1NP+N-MID-OT三指标联合检测用于预测PMOP的效能更高。PMOP骨折组的β-CTX、t-P1NP及N-MID-OT均明显高于PMOP未骨折组(t值依次为6.078、16.363、12.227,P<0.05)。β-CTX+t-P1NP+N-MID-OT联合检测用于评估PMOP骨折风险的AUC值为0.939,敏感度为94.87%,特异度为95.24%,表明β-CTX+t-P1NP+N-MID-OT联合检测用于评估PMOP骨折风险的效能更高。结论PMOP患者β-CTX、t-P1NP及N-MID-OT水平均明显升高,而PMOP骨折患者β-CTX、t-P1NP及N-MID-OT水平升高更为明显,且β-CTX+t-P1NP+N-MID-OT联合检测可显著提高对PMOP预测及骨折风险评估效能,值得借鉴。
基金supported by grants from the National Natural Science Foundation of China(21566024)。
文摘The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide(MP)on cyclophosphamide(CTX)induced liver injury in mice.To explore metabolic profile of liver tissue and feces among normal group,CTX-induced group and MP management group based on metabolomics method by using UPLC-Q-TOF/MS.The results showed that MP could alleviate liver injury and promote the production of short chain fatty acids(SCFAs),with the best dose of 200 mg/kg·body weight(bw).The principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLSDA)scores plots of the liver and feces samples showed a clear separation among normal,model and highdose of MP(MPH).There were 18 endogenous metabolites in liver and 29 endogenous metabolites in feces,which were mainly involved in 8 metabolic pathways:taurine and hypotaurine metabolism,phenylalanine metabolism,α-linolenic acid metabolism,tricarboxylic acid(TCA)cycle,phenylalanine,tyrosine and tryptophan biosynthesis,arachidonic acid metabolism,sphingolipid metabolism as well as tryptophan metabolism.Moreover,a common metabolite arachidonic acid was observed in liver and feces samples.These endogenous metabolites may be considered to be MP’s response to liver protection.It will help to further understand the mechanism of MP and provide a basis for further research.
基金Supported by Beijing Municipal Administration of Hospitals’Ascent Plan,No.DFL20180701and Beijing Municipal Grant for Medical Talents Group on Peritoneal Surface Oncology,No.2017400003235J007。
文摘BACKGROUND Pseudomyxoma peritonei(PMP)is a rare peritoneal malignant tumor syndrome.Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is its standard treatment.However,there are few studies and insufficient evidence regarding systemic chemotherapy of advanced PMP.Regimens for colorectal cancer are often used clinically,but there is no uniform standard for late-stage treatment.AIM To determine if bevacizumab combined with cyclophosphamide and oxaliplatin(Bev+CTX+OXA)is effective for treatment of advanced PMP.The primary study endpoint was progression-free survival(PFS).METHODS Retrospective analysis was conducted on the clinical data of patients with advanced PMP who received Bev+CTX+OXA regimen(bevacizumab 7.5 mg/kg ivgtt d1,oxaliplatin 130 mg/m2 ivgtt d1 and cyclophosphamide 500 mg/m2 ivgtt d1,q3w)in our center from December 2015 to December 2020.Objective response rate(ORR),disease control rate(DCR)and incidence of adverse events were evaluated.PFS was followed up.Kaplan-Meier method was used to draw survival curve,and log-rank test was used for comparison between groups.Multivariate Cox proportional hazards regression model was used to analyze the independent influencing factors of PFS.RESULTS A total of 32 patients were enrolled.After 2 cycles,the ORR and DCR were 3.1%and 93.7%,respectively.The median follow-up time was 7.5 mo.During the follow-up period,14 patients(43.8%)had disease progression,and the median PFS was 8.9 mo.Stratified analysis showed that the PFS of patients with a preoperative increase in CA125(8.9 vs 2.1,P=0.022)and a completeness of cytoreduction score of 2-3(8.9 vs 5.0,P=0.043)was significantly longer than that of the control group.Multivariate analysis showed that a preoperative increase in CA125 was an independent prognostic factor for PFS(HR=0.245,95%CI:0.066-0.904,P=0.035).CONCLUSION Our retrospective assessment confirmed that the Bev+CTX+OXA regimen is effective in second-or posterior-line treatment of advanced PMP and that adverse reactions can be tolerated.A preoperative increase in CA125 is an independent prognostic factor of PFS.
基金The authors acknowledge the support of the National Natural Science Foundation of China(No.81804171)Project of Guangdong Provincial Administration of Traditional Chinese Medicine(No.20241049)The Scientific Research Projects of Medical and Health Institutions of Longhua District,Shenzhen(No.2023063).
文摘Background:To explored whether moxa cone moxibustion can reduce peritoneal inflammation by increasing the content of peritoneal macrophages and B cells via interferon-gamma.Methods:The mice were randomly divided into three groups with six mice in each group:the control group,model group,and moxibustion group,and the model was established in mice using cyclophosphamide.In the moxibustion group,the mice received moxa cone moxibustion at Zusanli(ST36)for 7 days.Analysis of Peritoneal cell were detected by flow cytometry and immunofluorescence,the protein expression level in the peritoneal fluid were measured with mouse cytokine antibody arrays and verified by enzyme linked immuno sorbent assay test,and RNA-Sequencing was used for peritoneal cell RNA analysis.Results:Our results showed that moxa cone moxibustion could reduce the loss of large peritoneal macrophages and B1 cells(P<0.05).With the cytokine array analysis and enzyme linked immuno sorbent assay test of peritoneal fluid,we found that IFN‐γwas up-regulated in moxibustion group(P<0.05).There were 169 genes were down-regulated in the model group and up-regulated in the moxibustion group while 19 genes that were up-regulated in the model group and down-regulated in the moxibustion group via RNA-sequencing.Kyoto Encyclopedia of Genes and Genomes pathway analysis of 188 intersect differentially expressed genes were found that the top 3 pathways with the highest enrichment of up-regulated genes included Hematopoietic cell lineage,Inflammatory bowel disease and Malaria.The differentially expressed genes visualization protein-protein interaction network shows the top 10 genes including Ifng,Grb2,CCR7,CTLA4,CXCR5,Foxp3,kit,PRF1,CD5 and klrg1.Conclusion:These findings showed that moxa cone moxibustion can alleviate chemotherapy-induced diarrhea by reducing the loss of large peritoneal macrophages and B1 cells in the peritoneal cavity,possibly through up-regulating inflammatory bowel disease signaling pathway via interferon-gamma to regulate the survival and function of large peritoneal macrophages and B1 cells.
文摘Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.
基金Supported by the 211 Project of Jinan Universitythe Team Project of Natural Science Foundation of Guangdong Province (8351063201000003)+3 种基金the Popular Science Foundation of Science & Technology Bureau of Guangzhou City (2008KP055)the Natural Science Foundation of Guangdong Province (06025198)the Jinan University Natural Science Foundation (51204017)the Science and Technology Innovation Project for Undergraduates (cx08120)
文摘An experiment was conducted to compare the effects of two mouse thrombocytopenia models induced by cyclophosphamide at two different administration routes to determine a proper cyclophosphamide administration route that could cause stable thrombocytopenia. A suitable drug dosage that could induce thrombocytopenia in mouse efficiently with the definite administration route was then investigated. BALB/c mice were randomly divided into Normal, Model A and Model B groups. To Model A, 200 mg/kg of cyclophosphamide was given by vena caudalis injection as first dose and 30 mg/kg as maintenance dose by intraperitoneal injection at the following 6 days. To Model B, 150 mg/kg of cyclophosphamide was given by subcutaneous injection once a day for consecutive 3 days. All groups were under investigation for 15 days. The result suggested that a decrease in the number of blood platelets of Model B at the 7th day were significantly than that of Normal. Other platelet related indices like platelet distribution width, mean platelet volume and platelet-large cell ratio of Model B increased significantly in comparison with those of Normal group. The platelets count was reduced but fluctuated greatly, and more than half of the mice died in Model A. Therefore, subcutaneous injection of cyclophosphamide for 3 days was used for the cyclophosphamide dosage test. BALB/c mice were randomly divided into Normal, cyclophosphamide low dose （100 mg/kg）, medium dose （120 mg/kg） and high dose （140 mg/kg） groups. All groups were under investigation for 11 days. Though all 3 dosages successfully initiated thrombocytopenia as the platelets number dropped at the 7th day, the low dose was considered to be a suitable one that was of high efficacy and low toxicity. Thus, BALB/c mice challenged by subcutaneous injection of cyclophosphamide 100 mg/kg per day for 3 consecutive day is one simple, feasible and stable mouse thrombocytopenia model that could be used for pharmacodynamic test of the drugs which are supposed to have platelets increasing effect.
文摘The protective effect of a kind of purified polysaccharides extracted from Radix of Phytolacca acinosa Roxb,with a molecular weight of 10 KDa,on hematopoiesis was investigated.Average survival time of mice treated with cyclophosphamide (CY) 300 mg/kg once alone was 13.3 ± 7.2d(n=7) however,average survival time of mice treated with CY 300 mg/kg in com-bination with PAP-1 10 mg/kg,3 times/wk was 36.7± 16.4d(n=7,P<0.01).PAP-1,ip had benefi-cial effect on the recovery of the CY induced decrease of peripheral leukocyte number,and the nu-cleated bone marrow cell(BMC)number and[3￣H]TdR uptaken by BMC induced by rmGM-CSF in S180 bearing mice treated with CY,In mice,after the first ip treatment with CY 100 mg/kg on d7,the peripheral leukocyte number decreased on d9 and recovered to normal level about d13 to d15. Such recovery was accelerated by administrating PAP-1,10mg/kg, 3 times/wk.A significant in-crease of the activity to form colony in spleen(colony-forming unit in spleen, CFU-S_8, CUF-S12) in mice irradiated with 550 rad 6O￣Co γ-rays and an enhancement of proliferative response of BMC to rmGM-CSF treated with PAP-1,10mg/kg,3 times/wk, ip were observed.After PAP-1,10 mg/kg,ip once,a significant increase in the number of peripheral blood leukocytes and a rise in the serum of colony stimulating factor(CSF) were also confirmed.The types of CSF in serum were M-CSF and other hematopoietic growth factors,which were confirmed by using McAb of IL-3, GM-CSF and PcAb of M-CSF. These beneficial effects of PAP-1 on hematopoiesis may be related to its activityinducing CSFs and other hematopoietic growth factors and warrant further evaluation of its use-fulness.
基金Supported by a grant from National Natural Scientific Foundation of China (No:30030781)
文摘Objective:The aim of the study was to investigate the effects as well as the possible mechanisms of low dose γ-ray pre-irradiation on hepatic damage,DNA damage of peripheral lymphocytes and genetic material damage caused by high dosage of cyclophosphamide(CTX).Methods:Kunming strain male mice were randomly divided into five groups:control group,sham-irradiated group,low dose irradiation group(LDR group),cyclophosphamide chemotherapy group(CTX group) and low dose irradiation combined with chemotherapy group(LDR + CTX group).Having being raised for one week,all the mice were implanted subcutaneously with S180 cells in the left inguen(control group excluded).On days 8 and 11,mice of LDR and LDR + CTX groups were given 75 mGy whole-body γ-irradiation,30 h later mice of CTX and LDR + CTX groups were injected i.p.3.0 mg cyclophosphamide.All the mice were sacrificed on day 13.DNA damage of the peripheral lymphocytes was analyzed using single cell gel electrophoresis(SCGE);ALT activity,total protein(TP) and albumin(ALB) of the plasma were analyzed using automatic biochemistry analyzer;MDA content,SOD and GSH-PX activity of the hepatic homogenate were analyzed using chromometry;genetic material damage was analyzed using micronucleus frequency(MNF) of polychromatoerythrocytes(PCE) in bone marrow.Results:1.Differences of MDA contents,SOD and GSH-PX activity of hepatic homogenate between 5 groups had notable statistical significance(P < 0.01);in control group MDA content was the lowest,SOD and GSH-PX activity were the highest,while in CTX group MDA content was the highest,SOD and GSH-PX activity were the lowest;compared with CTX group MDA content decreased significantly(P < 0.01) and SOD and GSH-PX activity increased significantly(P < 0.05) in LDR + CTX group.2.Differences of ALT activity of plasma between 5 groups had no statistical significance(F = 1.262,P > 0.05).Differences of TP and ALB of plasma between 5 groups had statistical significance(F = 12.879 and 6.336 respectively,P < 0.01);TP and ALB in control group were higher than those of other groups and compared with sham-irradiated group,TP and ALB in LDR group elevated significantly(P < 0.05).3.Differences of DNA damage of peripheral lymphocytes had notable statistical significance(F = 6.383,P < 0.01);DNA damage in control group was the lightest,while DNA damage in CTX group was the severest;compared with CTX group,DNA damage in LDR + CTX group was much lighter(P < 0.05).4.MNF of PCE between 5 groups had remarkable significance(F = 179.652,P < 0.01);compared with control group and sham-irradiated group,MNF in CTX group increased significantly(P < 0.01);compared with CTX group,MNF in LDR + CTX group had a tendency of decline,which had no statistical significance(P > 0.05).Conclusion:1.CTX can damage the hepatic tissue through oxidative stress;75 mGy γ-irradiation before CTX chemotherapy can induce activities of anti-oxidative enzymes,promote elimination of free radicals,so as to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-dose chemotherapy.2.A 75 mGy γ-irradiation before CTX chemotherapy has no obvious effect on ALT activity of plasma,but may have protective effect on the protein synthesis function of liver.3.High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes;75 mGy γ-irradiation before chemotherapy may have certain protective effect on DNA damage.4.CTX has potent mutagenic effect,can cause significant increase of MNF of PCE;75 mGy γ-ray pre-irradiation did not show obvious protection against genetic toxicity of high-dose CTX chemotherapy.
基金The authors gratefully acknowledge the financial assistance from the Major Research Project(Project No.F-3/50/99 dated 3l-3-99)provided by the University Grants Commission(UGC),New Delhi,India
文摘Aim:To study the detrimental effects of cyclophosphamide on the testicular androgenic and gametogenic activities through endocrine inhibition and/or induction of oxidative stress in male albino rats and to evaluate the protective effect of ascorbic acid.Methods:The testicular△^(5),3β-hydroxysteroid dehydrogenase(HSD),17β-HSD,peroxidase and catalase activities along with the levels of malondialdehyde(MDA)and conjugated dienes in testicular tissue were measured for the evaluation of testicular oxidative stress.The plasma testosterone(T)level was measured by immunoassay.Various germ cells at stageⅦof spermatogenic cycle were quantified from testicular stained sections.Results:Cyclophosphamide treatment results in a significant inhibition in the testicular△^(5),3β-HSD and 17β-HSD activities,a decrease in plasma T level and a diminution in the counts of various germ cells.Moreover,this treatment was also associated with a significant inhibition of the peroxidase and catalase activities along with high levels of MDA and conjugated dienes in the testis.All these changes were reversed by ascorbic acid co-administration.Conclusion:Cyclophosphamide treatment at the dosage used caused testicular gametogenic and androgenic disorders as well as induced testicular oxidative stress that can be reversed by ascorbic acid co-administration.
