BACKGROUND Despite significant technical and training improvements, the incidence of postendoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP) has not significantly dropped. Although many studies have...BACKGROUND Despite significant technical and training improvements, the incidence of postendoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP) has not significantly dropped. Although many studies have evaluated the efficacy of various agents, e.g. nonsteroidal anti-inflammatory drugs, octreotide,antioxidants, administered via various dosages, routes(oral, intrarectal or parenteral), and schedules(before or after the procedure), the results have been conflicting.AIM To evaluate efficacy of three pharmacologic prophylactic methods for prevention of PEP.METHODS In this prospective, single-center randomized trial, patients who underwent firsttime ERCP for choledocholithiasis were randomly assigned to three groups. The first group received 600 mg N-acetylcysteine 15 min prior to ERCP, and perrectum administration of 50 mg indomethacin both prior to and after completion of the ERCP. The second group was administered only the 50 mg indomethacin per-rectum both prior to and after the ERCP. The third group was administeredper-rectum 100 mg indomethacin only after the ERCP, representing the control group given the guideline-recommended regimen. The primary end-point was PEP prevention.RESULTS Among the total 211 patients evaluated during the study, 186 fulfilled the inclusion criteria and completed the protocol. The percentages of patients who developed PEP in each of the three groups were not significantly different(χ2 =2.793, P = 0.247). Among the acute PEP cases, for all groups, 14 patients developed mild pancreatitis(77.77%) and 4 moderate. No severe cases of PEP occurred, and in all PEP cases the resolution was favorable. No adverse events related to the medications(digestive hemorrhage, rectal irritation, or allergies)occurred.CONCLUSION The efficacies of split-dose indomethacin and combined administration(Nacetylcysteine with indomethacin) for preventing PEP were similar to that of the standard regimen.展开更多
Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine ...Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.展开更多
Cadmium （Cd） is a reproductive toxicant that induces germ cell apoptosis in the testes. Previous studies have demonstrated that endoplasmic reticulum （ER） stress is involved in Cd-induced germ cell apoptosis. The ...Cadmium （Cd） is a reproductive toxicant that induces germ cell apoptosis in the testes. Previous studies have demonstrated that endoplasmic reticulum （ER） stress is involved in Cd-induced germ cell apoptosis. The aim of the present study was to investigate the effects of N-acetylcysteine （NAC）, an antioxidant, on Cd-induced ER stress and germ cell apoptosis in the testes. Male CD-1 mice were intraperitoneally injected with CdCl2 （2.0 mg kg^-1）. As expected, acute Cd exposure induced germ cell apoptosis in the testes, as determined by terminal dUTP nick-end labelling （TUNEL）. However, the administration of NAC alleviated Cd-induced germ ceil apoptosis in the testes. Further analysis showed that NAC attenuated the Cd-induced upregulation of testicular glucose-regulated protein 78 （GRP78）, an important ER molecular chaperone. Moreover, NAC inhibited the Cd-induced phosphorylation of testicular eukaryotic translation initiation factor 2a （elF2a）, a downstream target of the double-stranded RNA-activated kinase-like ER kinase （PERK） pathway. In addition, NAC blocked the Cd-induced activation of testicular X binding protein （XBP）-1, indicating that NAC attenuates the Cd-induced ER stress and the unfolded protein response （UPR）. Interestingly, NAC almost completely prevented the Cd-induced elevation of C/EBP homologous protein （CHOP） and phosphorylation of c-Jun N-terminal kinase （.INK）, two components of the ER stress-mediated apoptotic pathway. In conclusion, NAC protects against Cd-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in the testes.展开更多
AIM: To investigate the effects of N-acetylcysteine (NAC) on endoplasmic reticulum (ER) stress and tissue injury during liver ischemia reperfusion injury (IRI).
BACKGROUND: Toll-like receptor 2 and 4 (TLR2/4) may play important roles in ischemia-reperfusion (I/R) injury, and N-acetylcysteine (NAC) can prevent the generation of reactive oxygen species (ROS) induced by I/R inju...BACKGROUND: Toll-like receptor 2 and 4 (TLR2/4) may play important roles in ischemia-reperfusion (I/R) injury, and N-acetylcysteine (NAC) can prevent the generation of reactive oxygen species (ROS) induced by I/R injury. This study aimed to investigate the changes in TLR2/4 gene expression in the liver and lung after I/R injury with or without NAC pretreatment. METHODS: BALB/c mice were used in a model of partial hepatic I/R injury and randomly assigned to a sham-operated control group (SH), a hepatic ischemia/reperfusion group (I/R) or a NAC pretreated, hepatic I/R group (I/R-NAC). The levels of TNF-alpha in the portal vein and plasma alanine aminotransferase (ALT) were measured at 1 and 3 hours after reperfusion. The lung wet-to-dry ratio was measured, and the expression of TLR2/4 mRNA and protein in the liver and lung were assessed with RT-PCR and Western blotting at the same time points. RESULTS: Compared with the I/R group, the expression of TLR2/4 mRNA and protein in the liver and lung in the I/R-NAC group was decreased at the same time point (P<0.05). The levels of portal vein TNF-a and plasma ALT increased continuously in the l/R group at I and 3 hours of reperfusion compared with the SH group; however, they declined significantly in the group pretreated with NAC (P<0.05). The extent of lung edema was relieved in the I/R-NAC group compared with the I/R group (P<0.05). CONCLUSIONS: TLR2/4 was activated in the liver and lung in the process of partial hepatic I/R injury. NAC inhibited the activation of TLR2/4 and the induction of TNF-alpha resulting from I/R injury via modulating the redox state, thus it may mitigate liver and lung injury following partial hepatic I/R in mice.展开更多
We report a case of intravenous(IV) amiodarone drug induced liver injury(DILI).The patient received IV N-acetylcysteine(NAC) which resulted in a rapid improvement in liver enzymes.While the specific mechanisms for the...We report a case of intravenous(IV) amiodarone drug induced liver injury(DILI).The patient received IV N-acetylcysteine(NAC) which resulted in a rapid improvement in liver enzymes.While the specific mechanisms for the pathogenesis of IV amiodaroneDILI and the therapeutic action of IV NAC are both unknown, this case strongly implies at least some commonality.Because IV amiodarone is indicated for the treatment of serious cardiac arrhythmias in an intensive care unit setting, some degree of ischemic hepatitis is likely a cofactor in most cases.展开更多
BACKGROUND： Studies have reported the antioxidant effects of lead and cadmium in the central nervous system, but very few have addressed the combined toxicity of lead and cadmium. The mechanisms by which these combin...BACKGROUND： Studies have reported the antioxidant effects of lead and cadmium in the central nervous system, but very few have addressed the combined toxicity of lead and cadmium. The mechanisms by which these combined heavy metals are toxic, as well as how to protect cells from these agents, remains poorly understood. OBJECTIVE： Primary cultured rat cortical neurons were used to determine the effects of combined lead and cadmium on levels of glutathione peroxidase （GSH-Px）, superoxide dismutase （SOD）, catalase （CAT）, and acetylcholinesterase （ACHE）, as well as malondialdehyde （MDA）, and to evaluate the neuroprotective effects of N-acetylcysteine （NAC）. DESIGN, TIME AND SETTING An in vitro toxicological observation was performed at the Comparative Medicine Center of Yangzhou University from August 2007 to April 2008. MATERIALS： Lead acetate, cadmium acetate, and NAC were purchased from Sigma-Aldrich （St. Louis, USA）. Commercial kits of GSH-Px, SOD, CAT, ACHE, and MDA were purchased from Nanjing Jiancheng Bioengineering Institute, Nanjing, China. METHODS： The cerebral cortical neurons were isolated from newborn Sprague dawley rats at 24 hours after birth and primary cultured for 6 days. Thereafter, the cells were treated with a range of cadmium doses （0, 5.0, and 10.0μmol/L）, lead doses （0, 1.0, and 2.0 μmol/L）, or a combination of the two for 12 hours at 37℃in a 5% CO2 incubator, respectively. In addition, the cells were incubated with different doses of cadmium and/or lead and （0 and 50 μmol/L） NAC for 12 hours to assess the protective effects on cell survival. MAIN OUTCOME MEASURES： The activity of SOD, GSH-Px, CAT, and ACHE, as well as MDA content, in the cell lysates was detected using commercial kits. RESULTS： At 12 hours after treatment, compared to the control group, activity of GSH-Px, SOD, and AChE in the lead, cadmium, or combined treated cells was significantly decreased with increasing doses of cadmium/or lead （P 〈 0.05）, but CAT activity and MDA levels were significantly increased （P 〈 0.05）. The combination of cadmium and lead led to higher levels of toxicity than individual exposure. CONCLUSION： The degree of oxidative damage increased when the two heavy metals were combined. NAC protected neonatal cortical neurons by increasing activity of anti-oxidative enzymes and reducing lipid peroxidation, but the reduction was not statistically significant.展开更多
The purpose of this study was to assess the efficacy of alexidine（ALX）,alone and combined with N-acetylcysteine（NAC）,in eradicating two Enterococcus faecalis strain biofilms.The biofilms of E.faecalis ATCC 29212 a...The purpose of this study was to assess the efficacy of alexidine（ALX）,alone and combined with N-acetylcysteine（NAC）,in eradicating two Enterococcus faecalis strain biofilms.The biofilms of E.faecalis ATCC 29212 and the clinical isolate E.faecalis D1 were grown in the MBEC-high-throughput device for 24 h and were exposed to five twofold dilutions of ALX（2%–0.007 8%）alone and combined with100 mg？mL21NAC,for 1 and 5 min.Eradication was defined as 100%kill of biofilm bacteria.The Student’s t-test was used to compare the efficacy of the associations of the two irrigants.After 1-min contact time,ALX eradicated the biofilms at all concentrations except for 0.007 8%and 0.015 6%–0.007 8%with E.faecalis ATCC 29212 and E.faecalis D1,respectively.Similar results for eradication and concentration were obtained when it was combined with 100 mg？mL21NAC.After 5 min of contact time,ALX alone and combined with NAC eradicated all enterococci biofilms.ALX showed antimicrobial properties against the two E.faecalis strain biofilms tested at very low concentrations,and its combined use with NAC was not seen to enhance its activity.展开更多
We evaluated the protective effect of N-acetylcysteine (NAC) on immunity system irradiated by 12C6+ ion beam. Kun-Ming mice were whole-body irradiated by 12C6+ ion at doses of 0, 0.5, 1, 1.5, 2, 2.5 and 3 Gy. The resu...We evaluated the protective effect of N-acetylcysteine (NAC) on immunity system irradiated by 12C6+ ion beam. Kun-Ming mice were whole-body irradiated by 12C6+ ion at doses of 0, 0.5, 1, 1.5, 2, 2.5 and 3 Gy. The results showed that in saline group, the lymphocytes DNA double-strand breaks (DSBs), maleic dialdehyde, thymocytes number in G 0 /G 1 and apoptosis percentage increased with dose increment, and the levels of interferon-γ, glutathione, superoxide radical (SOD) and natural killer cells activity decreased with dose increment. However, there were no significant changes in NAC-treated group. The data indicated that pre-treatment with NAC could significantly remove the ROS by counteracting the glutamate, decrease excessive lipid peroxidation reaction and SOD damages, and protect DNA, lymphocytes and cytokines against irradiation.展开更多
Glucocorticoids (GCs) are one of the most widely used immunosuppressive and anti-inflammatory agents. However, their long term and systemic use is associated with adverse drug reactions including posterior subcapsular...Glucocorticoids (GCs) are one of the most widely used immunosuppressive and anti-inflammatory agents. However, their long term and systemic use is associated with adverse drug reactions including posterior subcapsular cataracts as one of its ocular complications. Balanced redox state is crucial for maintenance of lens transparency, and a high content of glutathione (GSH) in the lens is believed to play a key role in doing so. Depletion of GSH is implicated in the etiopathogenesis of dexamethasone-induced cataracts and, therefore, the present study was sought to evaluate the efficacy of a novel thiol antioxidant, N-acetylcysteine amide (NACA), in preventing dexamethasone-induced cataractogenesis. Cataract formation was induced by incubation of rat lenses with 5 μM dexamethasone. To assess whether NACA had a significant impact on dexamethasone-induced cataracts, the rat lenses were divided into four groups: 1) control group (Dulbecco’s Modified Eagle Medium (DMEM), 2) dexamethasone group (DMEM with 5 μM dexamethasone), 3) NACA-only group (50 μM NACA solution), and 4) NACA pretreatment group (50 μM NACA for 6 hours followed by 5 μM dexamethasone only for 18 hours). Lenses were cultured for 7 days at 37°C under 5% CO2. Lenses were evaluated daily using a dissecting microscope and photographed and graded for the development of opacity. The rat lenses in both the control and the NACA-only groups were clear, whereas all lenses within the dexamethasone-only group developed well-defined cataracts. Overall observations indicated that NACA inhibits cataract formation by limiting lipid peroxidation and increasing the ratio of GSH/GSSG in lens. Therefore, NACA can be developed into a potential adjunctive therapeutic option for patients undergoing therapy with GCs to inhibit glucocorticoid-induced cataracts.展开更多
Objective：To study the effects of N-acetylcysteine （NAC） on ischemia/ reperfusion （I/R）-induced myocyte apoptosis in diabetic rats. Methods：The I/R heart model was made by ligation of the left anterior descendin...Objective：To study the effects of N-acetylcysteine （NAC） on ischemia/ reperfusion （I/R）-induced myocyte apoptosis in diabetic rats. Methods：The I/R heart model was made by ligation of the left anterior descending coronary artery （LAD） close to its origin. The LAD was occluded for 30 min followed by removal of ligation to allow subsequent reperfusion for 3 h. 72 rats were randomly divided into two groups , non-diabetic group （C, n = 36） and diabetic group ,（D, n = 36）. The animals in C group were randomly reassigned into sham-operated group （CS, n = 12） , I/R group （C I/R, n = 12） and treated with NAC group （CN, n = 12）. The rats in D group were also reassigned to sham-operated group （DS, n = 12） , I/R group （DI/R, n = 12） and treated with NAC group （DN, n = 12）. Malondialdehyde （MDA） and creatine kinase isoenzyme-MB （CK-MB） were measured. Infarct size（IS/AAR%）, the apoptosis index（AI） by TUNEL staining, the number of the cells positive for Caspase-3 and positive expression index （PEI） were calculated. Results：After I/R, the IS/AAR%, CK-MB, MDA, AI and Caspase-3 PEI were higher in diabetic group than those in non-diabetic group. Treatment with NAC decreased the above parameters in both non-diabetic and diabetic rats, but the parameters in diabetic rats were higher than those in non-diabetic rats. Conclusion：Diabetic rat hearts are more susceptible to I/R-induced myocardial necrosis and myocyte apoptosis. NAC can decrease the infarct size and attenuate cardiomyocyte apoptosis in both non-diabetic and diabetic rats, but the therapeutic effects are less effective in diabetic rats than those in non-diabetic rats.展开更多
Premature trypsinogen activation and production of oxygen free radicals (OFR) are early pathogenic events which occur within acinar cells and trigger acute pancreatitis (AP). OFR exert their harmful effects on various...Premature trypsinogen activation and production of oxygen free radicals (OFR) are early pathogenic events which occur within acinar cells and trigger acute pancreatitis (AP). OFR exert their harmful effects on various cell components causing lipid peroxidation, disturbances in calcium homeostasis and DNA damage, which lead to increased cell injury and eventually cell death. This review presents the most recent data concerning the effects of N-Acetylcysteine (NAC), in the treatment of AP. NAC is an antioxidant capable of restoring the levels of Glutathione, the most important cellular antioxidant. Studies show the benef icial effects of NAC treatment in preventing OFR production and therefore attenuating oxidative damage. Additionally, NAC treatment has been shown to prevent the increase in cytosolic Ca2+ concentration and reduce the accumulation of enzymes in acinar cells during AP. The prevention, by NAC, of these pathological events occurring within acinar would contribute to reducing the severity of AP. NAC is also capable of reducing the activation of transcription factors especially sensitive to the cellular redox state, such as Nuclear factor-κB, signal transducer and activator of transcription-3 and mitogenactivated protein kinase. This leads to a down-regulation of cytokines, adhesion molecules and chemokine expression in various cell types during AP. These f indingspoint to NAC as a powerful therapeutic treatment, attenuating oxidative-stress-induced cell injury and other pathological events at early stages of AP, and potentially contributing to reducion in the severity of disease.展开更多
文摘BACKGROUND Despite significant technical and training improvements, the incidence of postendoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP) has not significantly dropped. Although many studies have evaluated the efficacy of various agents, e.g. nonsteroidal anti-inflammatory drugs, octreotide,antioxidants, administered via various dosages, routes(oral, intrarectal or parenteral), and schedules(before or after the procedure), the results have been conflicting.AIM To evaluate efficacy of three pharmacologic prophylactic methods for prevention of PEP.METHODS In this prospective, single-center randomized trial, patients who underwent firsttime ERCP for choledocholithiasis were randomly assigned to three groups. The first group received 600 mg N-acetylcysteine 15 min prior to ERCP, and perrectum administration of 50 mg indomethacin both prior to and after completion of the ERCP. The second group was administered only the 50 mg indomethacin per-rectum both prior to and after the ERCP. The third group was administeredper-rectum 100 mg indomethacin only after the ERCP, representing the control group given the guideline-recommended regimen. The primary end-point was PEP prevention.RESULTS Among the total 211 patients evaluated during the study, 186 fulfilled the inclusion criteria and completed the protocol. The percentages of patients who developed PEP in each of the three groups were not significantly different(χ2 =2.793, P = 0.247). Among the acute PEP cases, for all groups, 14 patients developed mild pancreatitis(77.77%) and 4 moderate. No severe cases of PEP occurred, and in all PEP cases the resolution was favorable. No adverse events related to the medications(digestive hemorrhage, rectal irritation, or allergies)occurred.CONCLUSION The efficacies of split-dose indomethacin and combined administration(Nacetylcysteine with indomethacin) for preventing PEP were similar to that of the standard regimen.
文摘Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.
基金ACKNOWLEDGMENTS This project was supported by the National Natural Science Foundation of China （No. 31000664） and Grants for Scientific Research of BSKY （No. XJ201114） and the Program of Young Top-Notch Talents from Anhui Medical University.
文摘Cadmium （Cd） is a reproductive toxicant that induces germ cell apoptosis in the testes. Previous studies have demonstrated that endoplasmic reticulum （ER） stress is involved in Cd-induced germ cell apoptosis. The aim of the present study was to investigate the effects of N-acetylcysteine （NAC）, an antioxidant, on Cd-induced ER stress and germ cell apoptosis in the testes. Male CD-1 mice were intraperitoneally injected with CdCl2 （2.0 mg kg^-1）. As expected, acute Cd exposure induced germ cell apoptosis in the testes, as determined by terminal dUTP nick-end labelling （TUNEL）. However, the administration of NAC alleviated Cd-induced germ ceil apoptosis in the testes. Further analysis showed that NAC attenuated the Cd-induced upregulation of testicular glucose-regulated protein 78 （GRP78）, an important ER molecular chaperone. Moreover, NAC inhibited the Cd-induced phosphorylation of testicular eukaryotic translation initiation factor 2a （elF2a）, a downstream target of the double-stranded RNA-activated kinase-like ER kinase （PERK） pathway. In addition, NAC blocked the Cd-induced activation of testicular X binding protein （XBP）-1, indicating that NAC attenuates the Cd-induced ER stress and the unfolded protein response （UPR）. Interestingly, NAC almost completely prevented the Cd-induced elevation of C/EBP homologous protein （CHOP） and phosphorylation of c-Jun N-terminal kinase （.INK）, two components of the ER stress-mediated apoptotic pathway. In conclusion, NAC protects against Cd-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in the testes.
基金Supported by First Affiliated Hospital of Nanjing Medical University and the National Natural Science Foundation of China,Grant No.81100270,No.81070380,No.81310108001,No.81210108017 and No.81273261
文摘AIM: To investigate the effects of N-acetylcysteine (NAC) on endoplasmic reticulum (ER) stress and tissue injury during liver ischemia reperfusion injury (IRI).
基金This work was supported by a grant from theNational Natural Science Foundation of China(No.30200272).
文摘BACKGROUND: Toll-like receptor 2 and 4 (TLR2/4) may play important roles in ischemia-reperfusion (I/R) injury, and N-acetylcysteine (NAC) can prevent the generation of reactive oxygen species (ROS) induced by I/R injury. This study aimed to investigate the changes in TLR2/4 gene expression in the liver and lung after I/R injury with or without NAC pretreatment. METHODS: BALB/c mice were used in a model of partial hepatic I/R injury and randomly assigned to a sham-operated control group (SH), a hepatic ischemia/reperfusion group (I/R) or a NAC pretreated, hepatic I/R group (I/R-NAC). The levels of TNF-alpha in the portal vein and plasma alanine aminotransferase (ALT) were measured at 1 and 3 hours after reperfusion. The lung wet-to-dry ratio was measured, and the expression of TLR2/4 mRNA and protein in the liver and lung were assessed with RT-PCR and Western blotting at the same time points. RESULTS: Compared with the I/R group, the expression of TLR2/4 mRNA and protein in the liver and lung in the I/R-NAC group was decreased at the same time point (P<0.05). The levels of portal vein TNF-a and plasma ALT increased continuously in the l/R group at I and 3 hours of reperfusion compared with the SH group; however, they declined significantly in the group pretreated with NAC (P<0.05). The extent of lung edema was relieved in the I/R-NAC group compared with the I/R group (P<0.05). CONCLUSIONS: TLR2/4 was activated in the liver and lung in the process of partial hepatic I/R injury. NAC inhibited the activation of TLR2/4 and the induction of TNF-alpha resulting from I/R injury via modulating the redox state, thus it may mitigate liver and lung injury following partial hepatic I/R in mice.
文摘We report a case of intravenous(IV) amiodarone drug induced liver injury(DILI).The patient received IV N-acetylcysteine(NAC) which resulted in a rapid improvement in liver enzymes.While the specific mechanisms for the pathogenesis of IV amiodaroneDILI and the therapeutic action of IV NAC are both unknown, this case strongly implies at least some commonality.Because IV amiodarone is indicated for the treatment of serious cardiac arrhythmias in an intensive care unit setting, some degree of ischemic hepatitis is likely a cofactor in most cases.
基金the National Natural Science Foundation of China,No.305713647Natural Science Foundation of Jiangsu Province,No. BK2008214
文摘BACKGROUND： Studies have reported the antioxidant effects of lead and cadmium in the central nervous system, but very few have addressed the combined toxicity of lead and cadmium. The mechanisms by which these combined heavy metals are toxic, as well as how to protect cells from these agents, remains poorly understood. OBJECTIVE： Primary cultured rat cortical neurons were used to determine the effects of combined lead and cadmium on levels of glutathione peroxidase （GSH-Px）, superoxide dismutase （SOD）, catalase （CAT）, and acetylcholinesterase （ACHE）, as well as malondialdehyde （MDA）, and to evaluate the neuroprotective effects of N-acetylcysteine （NAC）. DESIGN, TIME AND SETTING An in vitro toxicological observation was performed at the Comparative Medicine Center of Yangzhou University from August 2007 to April 2008. MATERIALS： Lead acetate, cadmium acetate, and NAC were purchased from Sigma-Aldrich （St. Louis, USA）. Commercial kits of GSH-Px, SOD, CAT, ACHE, and MDA were purchased from Nanjing Jiancheng Bioengineering Institute, Nanjing, China. METHODS： The cerebral cortical neurons were isolated from newborn Sprague dawley rats at 24 hours after birth and primary cultured for 6 days. Thereafter, the cells were treated with a range of cadmium doses （0, 5.0, and 10.0μmol/L）, lead doses （0, 1.0, and 2.0 μmol/L）, or a combination of the two for 12 hours at 37℃in a 5% CO2 incubator, respectively. In addition, the cells were incubated with different doses of cadmium and/or lead and （0 and 50 μmol/L） NAC for 12 hours to assess the protective effects on cell survival. MAIN OUTCOME MEASURES： The activity of SOD, GSH-Px, CAT, and ACHE, as well as MDA content, in the cell lysates was detected using commercial kits. RESULTS： At 12 hours after treatment, compared to the control group, activity of GSH-Px, SOD, and AChE in the lead, cadmium, or combined treated cells was significantly decreased with increasing doses of cadmium/or lead （P 〈 0.05）, but CAT activity and MDA levels were significantly increased （P 〈 0.05）. The combination of cadmium and lead led to higher levels of toxicity than individual exposure. CONCLUSION： The degree of oxidative damage increased when the two heavy metals were combined. NAC protected neonatal cortical neurons by increasing activity of anti-oxidative enzymes and reducing lipid peroxidation, but the reduction was not statistically significant.
基金supported by the Research Group CTS-167 of the Junta de Andaluc'a,Spain
文摘The purpose of this study was to assess the efficacy of alexidine（ALX）,alone and combined with N-acetylcysteine（NAC）,in eradicating two Enterococcus faecalis strain biofilms.The biofilms of E.faecalis ATCC 29212 and the clinical isolate E.faecalis D1 were grown in the MBEC-high-throughput device for 24 h and were exposed to five twofold dilutions of ALX（2%–0.007 8%）alone and combined with100 mg？mL21NAC,for 1 and 5 min.Eradication was defined as 100%kill of biofilm bacteria.The Student’s t-test was used to compare the efficacy of the associations of the two irrigants.After 1-min contact time,ALX eradicated the biofilms at all concentrations except for 0.007 8%and 0.015 6%–0.007 8%with E.faecalis ATCC 29212 and E.faecalis D1,respectively.Similar results for eradication and concentration were obtained when it was combined with 100 mg？mL21NAC.After 5 min of contact time,ALX alone and combined with NAC eradicated all enterococci biofilms.ALX showed antimicrobial properties against the two E.faecalis strain biofilms tested at very low concentrations,and its combined use with NAC was not seen to enhance its activity.
基金Supported by National Basic Research Program(973Program)(No.2010CB834202)National Natural Science Foundation of China(No.10835011)+1 种基金Key Scientific Technology Research Projects of Gansu Province(Nos.0702NKDA045 and 0801NKDA001)West Light Foundation(Doctor aid,2009)
文摘We evaluated the protective effect of N-acetylcysteine (NAC) on immunity system irradiated by 12C6+ ion beam. Kun-Ming mice were whole-body irradiated by 12C6+ ion at doses of 0, 0.5, 1, 1.5, 2, 2.5 and 3 Gy. The results showed that in saline group, the lymphocytes DNA double-strand breaks (DSBs), maleic dialdehyde, thymocytes number in G 0 /G 1 and apoptosis percentage increased with dose increment, and the levels of interferon-γ, glutathione, superoxide radical (SOD) and natural killer cells activity decreased with dose increment. However, there were no significant changes in NAC-treated group. The data indicated that pre-treatment with NAC could significantly remove the ROS by counteracting the glutamate, decrease excessive lipid peroxidation reaction and SOD damages, and protect DNA, lymphocytes and cytokines against irradiation.
文摘Glucocorticoids (GCs) are one of the most widely used immunosuppressive and anti-inflammatory agents. However, their long term and systemic use is associated with adverse drug reactions including posterior subcapsular cataracts as one of its ocular complications. Balanced redox state is crucial for maintenance of lens transparency, and a high content of glutathione (GSH) in the lens is believed to play a key role in doing so. Depletion of GSH is implicated in the etiopathogenesis of dexamethasone-induced cataracts and, therefore, the present study was sought to evaluate the efficacy of a novel thiol antioxidant, N-acetylcysteine amide (NACA), in preventing dexamethasone-induced cataractogenesis. Cataract formation was induced by incubation of rat lenses with 5 μM dexamethasone. To assess whether NACA had a significant impact on dexamethasone-induced cataracts, the rat lenses were divided into four groups: 1) control group (Dulbecco’s Modified Eagle Medium (DMEM), 2) dexamethasone group (DMEM with 5 μM dexamethasone), 3) NACA-only group (50 μM NACA solution), and 4) NACA pretreatment group (50 μM NACA for 6 hours followed by 5 μM dexamethasone only for 18 hours). Lenses were cultured for 7 days at 37°C under 5% CO2. Lenses were evaluated daily using a dissecting microscope and photographed and graded for the development of opacity. The rat lenses in both the control and the NACA-only groups were clear, whereas all lenses within the dexamethasone-only group developed well-defined cataracts. Overall observations indicated that NACA inhibits cataract formation by limiting lipid peroxidation and increasing the ratio of GSH/GSSG in lens. Therefore, NACA can be developed into a potential adjunctive therapeutic option for patients undergoing therapy with GCs to inhibit glucocorticoid-induced cataracts.
文摘Objective：To study the effects of N-acetylcysteine （NAC） on ischemia/ reperfusion （I/R）-induced myocyte apoptosis in diabetic rats. Methods：The I/R heart model was made by ligation of the left anterior descending coronary artery （LAD） close to its origin. The LAD was occluded for 30 min followed by removal of ligation to allow subsequent reperfusion for 3 h. 72 rats were randomly divided into two groups , non-diabetic group （C, n = 36） and diabetic group ,（D, n = 36）. The animals in C group were randomly reassigned into sham-operated group （CS, n = 12） , I/R group （C I/R, n = 12） and treated with NAC group （CN, n = 12）. The rats in D group were also reassigned to sham-operated group （DS, n = 12） , I/R group （DI/R, n = 12） and treated with NAC group （DN, n = 12）. Malondialdehyde （MDA） and creatine kinase isoenzyme-MB （CK-MB） were measured. Infarct size（IS/AAR%）, the apoptosis index（AI） by TUNEL staining, the number of the cells positive for Caspase-3 and positive expression index （PEI） were calculated. Results：After I/R, the IS/AAR%, CK-MB, MDA, AI and Caspase-3 PEI were higher in diabetic group than those in non-diabetic group. Treatment with NAC decreased the above parameters in both non-diabetic and diabetic rats, but the parameters in diabetic rats were higher than those in non-diabetic rats. Conclusion：Diabetic rat hearts are more susceptible to I/R-induced myocardial necrosis and myocyte apoptosis. NAC can decrease the infarct size and attenuate cardiomyocyte apoptosis in both non-diabetic and diabetic rats, but the therapeutic effects are less effective in diabetic rats than those in non-diabetic rats.
文摘Premature trypsinogen activation and production of oxygen free radicals (OFR) are early pathogenic events which occur within acinar cells and trigger acute pancreatitis (AP). OFR exert their harmful effects on various cell components causing lipid peroxidation, disturbances in calcium homeostasis and DNA damage, which lead to increased cell injury and eventually cell death. This review presents the most recent data concerning the effects of N-Acetylcysteine (NAC), in the treatment of AP. NAC is an antioxidant capable of restoring the levels of Glutathione, the most important cellular antioxidant. Studies show the benef icial effects of NAC treatment in preventing OFR production and therefore attenuating oxidative damage. Additionally, NAC treatment has been shown to prevent the increase in cytosolic Ca2+ concentration and reduce the accumulation of enzymes in acinar cells during AP. The prevention, by NAC, of these pathological events occurring within acinar would contribute to reducing the severity of AP. NAC is also capable of reducing the activation of transcription factors especially sensitive to the cellular redox state, such as Nuclear factor-κB, signal transducer and activator of transcription-3 and mitogenactivated protein kinase. This leads to a down-regulation of cytokines, adhesion molecules and chemokine expression in various cell types during AP. These f indingspoint to NAC as a powerful therapeutic treatment, attenuating oxidative-stress-induced cell injury and other pathological events at early stages of AP, and potentially contributing to reducion in the severity of disease.
