Acute and Sub-Chronic Toxicity Evaluation of the Crude Methanolic Bark Extract of Bridelia micrantha (Hochst.) Baill. (Phyllanthaceae) and Its Fraction

Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of the stem bark of Bridelia micrantha using column chromatographic techniques. The fraction F6 was the most active when tested for antibacterial activity. Thus, toxicity of this fraction was investigated for further use. The present study evaluated the acute and sub-chronic toxicity of the crude methanolic bark extract of Bridelia micrantha and its fraction. The acute toxicity was carried out according to the experimental protocol of Organization for Economic Co-operation and Development (OECD). The plant extract or the fraction F6 was administered orally to female mice at a single dose of 2000 mg/kg and the animals were observed for any behavioral changes or mortality for 14 days. In the sub-chronic toxicity study, the extract and fraction were administered orally at 200, 400 and 800 mg/kg bw/day for 28 days to healthy Wistar rats. The general behavior and body weight of the rats were recorded daily. At the end of the experimental period, hematological and biochemical analyses, changes in vital organ weight (liver, lung, heart, spleen and kidney), and histopathological examination of the liver and kidney were performed. No mortality or adverse effects were noted at the 2000 mg/kg dose during the oral acute toxicity test. In the sub-chronic study, the crude methanolic bark extract of Bridelia micrantha and the fraction F6 induced no mortality or treatment-related adverse effects on body weight, general behavior, relative organ weights, hematological and biochemical parameters. Histopathological examination of the liver and kidney showed normal architecture suggesting no morphological alterations. In conclusion, the oral administration of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 for 28 days at a dosage of up to 800 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD50) of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 was estimated to be more than 2000 mg/kg.

Acute and Sub-chronic Toxicity of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. Br. in Beagle Dogs

Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establish the toxicity profile of the alkaloid extract(TA)of A.scholaris leaves in non-rodents.After oral administration of a single dose(4 g/kg.bw),a num-ber of transient symptoms,such as unsteady gait,drooling,emesis,and reddening of peri-oral mucosa,were observed,but no treatment-related mortality.A sub-chronic toxicity study with a range of doses of TA(20,60 and 120 mg/kg.bw)was conducted for a 13-week treatment period,followed by 4-week recovery observation.Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group,no clinical changes were observed in TA-treated animals.Data from electrocardiography,bone marrow,urine,fecal,hematology and clinical chemistry analyses were comparable between TA-treated and control animals.No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups.Accordingly,the non-observed-adverse-effect-level(NOAEL)of TA was established as 120 mg/kg.bw.Our results add further knowledge to the safety database for indole alkaloid extracts from A.scholaris with potential utility as novel drug candidates.

Sub-chronic Toxicity Test of Tephrosia canadida DC. in Mice

[ Objective] To observe sub-chronic toxicity of Tephrosia canadida DC. in mice and thus to evaluate their safety to be used as protein feed resources. [ Methed]Sixty-four 6-week-old healthy Kunming mice weighing about 25 g were randomly divided into four groups （ n = 16）, half male and half female. Mass ratios of basic diet to leaf meal of Tephrosia canadida DC. in group A, group B, group C and group D were 10：0, 4：1, 3：2 and 2：3, respectively. After 35-d feeding, the effects of Tephrosia canadida DC. on growth, blood and organs of mice were observed. [ Resultl Dudng the trial, all mice had normal activities, and no death and no abnormal blood index were observed. All organs of the mice in the experimental groups had no visible pathological lesion, and organ indexes had no significant difference between the experimental groups and the control group. Except that slightly abnormal histological changes appeared in liver and kidney of the mice in the group C and D, no histological change was ob- served in other organs of the experimental mice. [ Conclusion] Tephrosia canadida DC. have no adverse effects on mice, which provides a refer- ence for research about their safety in feed of other animals.

Evaluating the safety of forsythin from Forsythia suspensa leaves by acute and sub-chronic oral administration in rodent models

Objective: To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety,Methods: Acute toxicity was determined by oral administration of a single dose of 18 100 mg/kg forsythin in NIH mice,Sub-chronic toxicity was evaluated by oral administration of several doses of forsythin for 30 days at does of 0,540,1 620,and 6 480 mg/kg in SD rats.Results: In the acute toxicity study,mortality was not observed after 14 days,In addition,clinically relevant adverse effects,or variations in body weight or food consumption were not observed,Similarly,after 30 days in the sub-chronic toxicity study,no mortality or significant toxicological effects such as decreased food consumption,body weight,biochemical parameters and vital organs etc,were noticed,Conclusion: The results revealed that the forsythin from Forsythia suspensa leaves has low or no toxicity via oral administration,and therefore is suitable for further development and applications.

Subchronic Oral Toxicity Evaluation of Lanthanum： A 90-day, Repeated Dose Study in Rats

Objective The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level（NOAEL）,which is a critical factor in the establishment of an acceptable dietary intake（ADI）.Methods In accordance with the Organization for Economic Co-operation and Development（OECD） testing guidelines,lanthanum nitrate was administered once daily by gavage to Sprague-Dawley（SD） rats at dose levels of 0,1.5,6.0,24.0,and 144.0 mg/kg body weight（BW） per day for 90 days,followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups.Outcome parameters were mortality,clinical symptoms,body and organ weights,serum chemistry,and food consumption,as well as ophthalmic,urinary,hematologic,and histopathologic indicators.The benchmark dose（BMD） approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.Results Significant decreases were found in the 144.0 mg/kg BW group in the growth index,including body weight,organ weights,and food consumption.This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day.Importantly,the 95% lower confidence value of the benchmark dose（BMDL） was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.Conclusion The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements（REEs）.

Subacute oral toxicity study of ethanolic leaves extracts of Strobilanthes crispus in rats

Objective:To examine the oral toxicity of repeated dosing of Strobilanthes crispus(S.crispus)ethanol leaves extract on the liver and kidney functions in Sprague Dawley rats.Methods:Young female rats aged between 8 and 12 week-old were randomly assigned into four groups with five animals each group(n=5).The first group served as control,while the second,third and fourth groups were orally treated with a single dose daily with 150 mg/kg,300 mg/kg,and600 mg/kg of S.crispus ethanol leaves extract for 14 d consecutively.Cage-side observation was conducted for first 4h after each dosing.The body weight changes,food consumptions and water intake were also recorded.Serum biochemical parameters,i.e.,aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,creatinine and urea were determined at Day15.All results were expressed as mean±SD and analysed using Dunnett's test.Results:It was obtained that 14-day oral administration of S.crispus ethanol leaves extract did not cause any adverse effects or lethality to the female Sprague Dawley rats,No significant changes in serum biochemical parameters,relative organs weights,body weights,food intake and water consumptions were observed between the treatment groups and control.Conclusions:In conclusion,14-day oral administration of S.crispus ethanol leaves extract was safe to be consumed in female rats without affecting the liver and kidney Functions.

Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats

Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na)and to determine the point of departure(POD),which is a critical factor in the establishment of an acceptable dietary intake.Methods DHA-Na was administered once daily by gavage to Sprague–Dawley rats at dose levels of 0.0,31.0,62.0,and 124.0 mg/kg BW per day for 90 days,followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups.The outcome parameters were mortality,clinical observations,body weights,food consumption,hematology and clinical biochemistry,endocrine hormone levels,and ophthalmic,urinary,and histopathologic indicators.The benchmark dose(BMD)approach was applied to estimate the POD.Results Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate,whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group.Importantly,the 95%lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.Conclusion The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels(62.0 and 124.0 mg/kg BW)after a 90-day oral exposure.

Acute and 26-Week Repeated Oral Dose Toxicity Study of UP446, a Combination of <i>Scutellaria</i>Extract and <i>Acacia</i>Extract in Rats

UP446 has been used in both joint supplements and prescription medical food. The purpose of this study was to evaluate the pharmaceutical safety of UP446 via acute and 26-week repeated oral dose toxicity study in SD rats. In acute toxicity study, UP446 was administered by oral gavage to Sprague-Dawley rats (5 males and 5 females) at a dose of 5000 mg/kg. In 26-week repeated oral dose toxicity study, UP446 at doses of 500, 1000 and 2000 mg/kg/day were given orally to groups of rats (10 rats/dose/sex) for 26-week. UP446 at a dose of 5000 mg/kg produced no treatment-related acute toxicity or mortality in any of the animals tested during 14 days of the study. In 26-week repeated dose toxicity study, there was no significant difference in body weight between the control and all treatment groups. Blackish stool and soft stool was observed in one male in the 1000 mg/kg group and in some males and females of 2000 mg/kg group. However, these changes of stool were not considered to be toxic effects because neither histopathological change in gastrointestinal tracks (GIT) nor body weight change were detected. No drug induced abnormalities were found as of body weights, food consumption, ophthalmological examinations, urinalysis, hematology, clinical chemistry, organ weights and gross necropsy in any animals in the dosing groups. These results suggest that the oral lethal dose of UP446 for male and female rats is in excess of 5000 mg/kg and the no observed adverse effect level (NOAEL) of the UP446 for both male and female rats is considered to be greater than 2000 mg/kg/day.

Effects of Sub-chronic Intoxication of 1,8-cineole on Blood Biochemical Indexes of Mice

[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17 g were randomly divided into four groups （forty mice per group）. Mice were injected to 1, 8 - cineole with doses of 192.45,64. 15 and 21.38 mg/kg body weight （ test groups） and the water solution of tween-80 with a volume fraction of 0.5% （ control group） respectively. Each mouse was administered orally at the dose of 0.2 mL per 10 g body weight once a day consecutively for 90 d. The body weight, routine blood indexes and serum biochemical indexes of mice were determined on the 30^th d, 60^th d, 90^th d and the 30^th d after stopping the administration of 1,8-cineole. [ Result] The effects of 1, 8-cineole on the body weight, routine blood indexes and serum biochemical indexes of mice with the doses of 64.15 and 21.38 mg/kg body weight had no statistically significant difference compared with the control group （P 〉0.05 ）. 1, 8-cineole with the dose of 192.45 mg/kg body weight exhibited different influences on routine blood indexes and serum biochemical indexes of mice after the oral administration of 1,8-cineole for 60 d and 90 d, and statistically significant differences in many blood biochemical indexes were observed （P 〈 0.05 ）. However, the differences in routine blood indexes and serum biochemical indexes were not statistically significant between the test groups and the control group at the 30＇h d after stopping the administration of 1, 8-cineole （ P 〉 0.05）. [Condusion] 1,8-cineole had sub-chronic oral toxicity to mice. The no observed adverse effect level （NOAEL） of 1,8-cineolc was 64.15 mg/kg body weight and the lowest observed adverse effect level （LOAEL） of 1,8-cineole was 192.45 mg/kg body weight. Effects of 1, 8-cineole on blood biochemical indexes of mice were in short term and reversible.

Subchronic Oral Toxicity of Pyridostigmine Bromide in Rats

This study evaluated the oral toxicity of pyridostigmine bromide in Sprague-Dawley rats when administered for 13 weeks by daily gavage. Groups of 10 rats/sex received doses of 0, 5, 15, 30, or 60 mg/kg/day. Toxicity was limited to exaggerated cholinergic stimulation at doses of 15 mg/kg/day or greater. Significant findings included tremors and inhibition of RBC acetylcholinesterase. Thus, 5 mg/kg/day of pyridostigmine bromide appears to be the no observed toxic effect level under the conditions of the present investigation.

Acute Toxicity of Aluminium Phosphide Following Oral Administration in Rats

Aluminium phosphide (AlP) is used as a fumigant and also sometimes misused for suicidal attempts in India, due to its easy availability. The effect of phosphine, the gas that is liberated when AlP comes in contact with moisture, is well documented in the literature. However, the effect of AlP in its native form on animal models is not well cited. In this study we examined the acute toxic effect of AlP in rats. Oral LD50 of AlP for male and female rats were found to be 14. 13 and 11. 89mg/kg, respectively. Oral administration of an AlP dose of 0. 80 LD50 resulted in significant increases in the level of plasma glutamic oxaloacetic transaminase,alkaline phosphatase, glucose and urea in rats of both sexes. Hemoglobin level and packed cell volume also increased significantly 6h after administration. Body weight was reduced but the organ to body weight ratio of lung, liver, spleen, kidney and testes remained unchanged.Histopathological changes induced by AlP during 24-48h induced hemorrhage, congestion and mild to moderate atrophy of various cellular components of visceral organs. The study showed that the acute toxic effect of AlP may be due to hypovolemic shock. Female rats were found to be more susceptible than were males.

Arsenic toxicity in mice and its possible amelioration

Oral administration of arsenic trioxide(3 and 6 mg/kg body weight/d) for 30 d caused, as compared with vehicle control, dose dependent significant reductions in body weight, absolute weight, protein, glycogen, as well as, total, dehydro and reduced ascorbic acid contents both in the liver and kidney of arsenic treated mice. Succinic dehydrogenase(SDH) and phosphorylase only in the liver activities were significantly reduced in a dose dependent manner. Acid phosphatase activity was significantly decreased in the liver of low dose arsenic treated animals; however, significant rise in its activity was observed in high dose group. As compared with vehicle control, treatment also caused significant dose dependent reductions in SDH, alkaline phosphatase and acid phosphatase activities in the kidney of mice. Vitamin E cotreatment as well as, 30 d withdrawal of arsenic trioxide treatment with or without vitamin E caused significant amelioration in arsenic induced toxicity in mice. Administration of vitamin E during withdrawal of treatment also caused significant amelioration as compared from only withdrawal of the treatment. It is concluded that vitamin E ameliorates arsenic induced toxicities in the liver and kidney of mice.

Synthesis, hypoglycemic activity and toxicity study of vanadium oxide complex with genistein

OBJECTIVE Vanadium is a necessary trace element in the human body and has a certain role in the treatment and prevention of diabetes.Organic vanadium is more easily absorbed and less toxic than inorganic vanadium.Thus,in this study,vanadium complex was synthesized from genistein which had good hypoglycemic activity and inor⁃ganic vanadium element,and its hypoglycemic activity and acute oral toxicity were studied.METHODS The vanadium genistein complex was synthesized by chelating vanadium with genistein in methanol and its structure was determined by LC-MS,atomic absorption spectroscopy,UV-visible spectroscopy,elemental and thermodynamic analysis.The antidiabetic activity of the complex was assessed in db/db mice and C57 mice by daily oral gavage for 4 weeks.These db/db mice were divided into test groups〔high(30 mg·kg^-1),medium(20 mg·kg^-1)and low(10 mg·kg^-1)dose group〕,model group,genistein group,inorganic vanadium group,each group of 8;8 C57 mice was for normal control group.The acute toxicity test was carried out on KM mice with this complex by a maximum limit dose method.Randomly 20 healthy KM mice were divided into negative control group and test group,each group of 10,male and female half.RESULTS The molecular structure of this complex was inferred as a complex(VL2)formed by two ligands and one vanadium element.It was found that its hypoglycemic activity was better than that of genistein and inorganic vanadium.The hypoglycemic activity of the high dose group was better than that of the medium dose group and low dose group.The complex can signifi⁃cantly improve the body mass of db/db mice,fasting blood glucose,random blood glucose,liver/body,kidney/body,and the performance of oral glucose tolerance test and insulin tolerance test in db/db mice.The morphology of liver,kidney,pancreas and skeletal muscle also had obvious improvement and repair.Effect on serum index of db/db mice showed that,total cholesterol,triglyceride,low-density lipoprotein cholesterol had no significant improvement compared with the model group,but high-density lipoprotein cholesterol of complex group had significant improvement compared with the model group.In addition,this complex did not produce any hazardous symptoms or deaths in acute oral toxicity test.CONCLUSION complex has good hypoglycemic activity in vivo,and did not have the potential toxicity.This would provide an important reference for the development of functional hypoglycemic foods.

Sub-chronic(Ninety Days)Toxicity Study of Hydroethanolic Leaf Extract of Datura stramonium L.in Rodents

Background:Phyto-medicine represents a vast pool of novel drug development,but understanding their safety requires elaborate,multifaceted approaches,including toxicity studies.Objective:This study investigated the effects of 90 days of oral administration of Datura stramonium(DSE)leaf extract in Rats.Methods:In the oral acute toxicity study,mice were treated with a single oral gavage of DSE at 500,1000,and 2000 mg·kg^(-1)/d,po and observed for signs of acute toxicity for 14 days.In the sub-chronic study,rats were randomized into four Groups(A-D).Group A received distilled water(10 mL·kg^(-1),po)while groups B-D received DSE(10,50 and 250 mg·kg^(-1)/d,po,respectively)orally for 90 days uninterrupted.Animals were weighed weekly,with food and water measured daily and relevant parameters assayed at the end of the 90days administration.Results:In acute toxicity studies,oral administration of up to 2 g·kg^(-1)/d,po of DSE did not elicit any semblance of toxicity or mortality within 24 h to 14 days.In the 90days studies,DSE(250 mg·kg^(-1)/d,po)decreased the body weight,brain weight,and food intake in female rats.DSE(10-250 mg·kg^(-1)/d,po)increased the red blood cell(RBC),packed cell volume(PCV)and hemoglobin(Hb)in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the triglycerides(TG),cholesterol and low-density lipoprotein(LDL);and decreased HDL in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the white blood cells(WBC)and platelets in female rats.DSE(10-250 mg·kg^(-1)/d,po)decreased the alkaline phosphatase(ALP)and alanine transaminase(ALT)in both studies.Serum urea level was decreased in both sexes.DSE(250 mg·kg^(-1)/d,po)decreased male rats’serum sodium ion levels.Liver,brain,testes and kidney showed severe lesions at 250 mg·kg^(-1)/d,po of the extract.Conclusion:D.stramonium is safe on acute exposure and relatively safe on sub-chronic oral administration.How-ever,prolonged use,especially at high doses,could cause Liver,brain and kidney toxicities;and abnormal lipid metabolism.

金属纳米酶在菌斑生物膜相关口腔疾病防治中的研究进展

口腔菌斑生物膜作为多种细菌生存、代谢的基础,使口腔细菌难以被清除。随着抗生素滥用造成的耐药菌群出现,菌斑生物膜相关口腔疾病的防治难度进一步增加。尽管目前在研究生物膜形成、破坏有关机制方面取得了一定进展,但可用于临床的有效治疗方案仍较缺乏。金属纳米酶具有纳米粒子的物理特性及类似天然酶的催化活性。金属纳米酶的纳米级尺寸提供了更大的比表面积,在发挥类酶作用产生大量活性氧的同时促进活性氧快速扩散到活性催化位点,增强纳米酶的抗氧化特性;同时金属纳米酶易通过电化学还原法、溶剂热合成法、微波辅助合成法等方法制取,且具有产生高浓度的羟基自由基、催化牙菌斑生物膜降解、氧化应激裂解葡聚糖抑制生物膜形成、释放金属离子杀灭细菌的潜力,有望成为防治口腔菌斑生物膜相关口腔疾病的新选择。金属纳米酶可通过口服、静脉注射、呼吸等方式进入生物体,但可能引发肺毒性、肝脏毒性、神经毒性等潜在毒性效应。在复杂的生物环境下,金属纳米酶毒性的发生可能涉及多重机制,其作用机制和安全性评价有待深入研究。本文拟从金属纳米酶的特性、抗菌机制、生物毒性及其在菌斑生物膜相关口腔疾病防治中的应用等多个方面阐述金属纳米酶的研究进展,为口腔疾病的防治提供新思路。

天冬对大鼠的亚慢性和致畸毒性研究

目的:研究天冬对大鼠经口重复给药的亚慢性毒性和致畸毒性。方法:90天经口毒性试验采用SD大鼠80只,雌雄各半,体质量65.4~94.0 g,拌饲法设2 000、4 000、8 000 mg/kg共3个剂量组和1个阴性对照组,连续给予受试物90天,观察动物一般状况,记录动物体质量、摄食量,计算食物利用率,并进行血液学、血生化及病理学检测,从而评价其亚慢性毒性。传统致畸试验采用雌性SD孕鼠,剂量为1 000、2 000、4 000 mg/kg共3个剂量组,另设阴性对照组(蒸馏水),每组22只,经口灌胃给药,于孕第20天处死母体,检查受孕情况和胎仔发育,观察胎仔外观,检查骨骼及内脏,以评估致畸毒性。结果:90天经口毒性试验中大鼠未出现中毒症状及死亡,试验组大鼠组织病理学检查未见毒性损伤作用。致畸试验中低、中剂量组胎仔胸骨发育不全发生率分别为21.49%和26.32%,与对照组(6.25%)相比显著升高(P<0.01),未见其他异常。结论:在本试验条件下,90天经口毒性试验中天冬对大鼠的未观察到有害作用剂量(NOAEL)为8 000 mg/kg;在致畸试验中,未观察到与染毒剂量相关的效应,天冬对SD大鼠无致畸性。

Modulation of the in vitro Oxidative Stress and Erythrocyte Cell Membrane Integrity Using Aqueous, Hydroethanolic and Ethanolic Stem-Barks Extracts of Greenwayodendron suaveolens (Engl. & Diels) Verdc

Pneumonia, a respiratory infection induces acute or chronic inflammation, characterized by increased activity of lymphocytes and neutrophils, thus generating oxygen-free radicals that decrease the endogenous antioxidants defence system. The aim of this experimental study focused on the capacity of nontoxic aqueous, hydroethanolic and ethanolic extracts of Greenwayodendron suaveolens (Engl. & Diels) Verdc. subsp. suaveolens to regulate free reactive species and protein inflammation generated by infectious disease. The phytochemical screenings of G. suaveolens extracts were carried out according to precipitation and colorimetric methods. The total antioxidant and flavonoid contents were determined by the Folin-Ciocalteu and Aluminium Chloride ethanolic methods. The efficiency of G. suaveolens extracts on free radicals was evaluated using DPPH•, ABTS+•, and FRAP methods. The anti-inflammatory properties of extracts were evaluated according to in vitro protein (BSA) denaturation, Proteinase Inhibitory Action, and Red Blood Cell Membrane stabilization assays. The G. suaveolens aqueous, hydroethanolic and ethanolic extracts were used for the acute toxicity assessment according to the OECD protocol. The obtained results showed the presence of flavonoids, phenols, polyphenols, tannins, anthocyanins, alkaloids, terpenoids, and sterols as secondary metabolites families in G. suaveolens extracts. The highest contents of total antioxidants and flavonoids were highlighted in the hydroethanolic extract. However, it’s the G. suaveolens aqueous extract that showed the best free radical DPPH• and ABTS+• scavenging activities (SC50) of 11.06 μg/mL and 15.16 μg/mL respectively. The highest ferric-reducing activity was found in G. suaveolens ethanolic extract with 866.23 μg EGA/mg of dry weight. The hydroethanolic extract has shown a high anti-inflammatory activity through BSA denaturation and erythrocyte membrane haemolysis with inhibitory concentrations 50 (IC50) of 48.63 and 59.22 μg/mL respectively. In contrast, proteinase inhibitory activity revealed a better potential of IC50 (34.19 μg/mL) for the ethanolic extract. In oral acute toxicity, all treated groups revealed neither mortality nor any significant alteration in behaviour and locomotion. The lethal dose 50 (LD50) of G. suaveolens extracts was >5000 mg/kg. These results suggest that G. suaveolens stem-barks extracts may serve as therapeutic sources to prevent inflammation induced by oxidative stress, an important feature of infectious diseases.

一种新型唇霜产品的制备方法及其功效评价

使用35 wt%高含量的PEG-5季戊四醇醚和PPG-5季戊四醇醚(“类羊毛脂”)结合助乳化剂甘油硬脂酸酯,作为唇部护理产品中的乳化剂和润肤剂,所制备的唇霜产品无急性经口毒性、无致敏性。在使用28天后,受试者唇部角质层水分含量显著提升56.11%(P<0.05),经表皮失水率降低17.27%,唇部光泽度提升27.89%,下唇唇纹体积、面积和深度分别改善35.01%、28.91%和12.13%,唇部皮肤颜色提亮2.77%。100%受试者认为该唇霜温和无刺激,90.91%受试者从整体上认同该产品。

Treatment-related gastrointestinal toxicities and advanced colorectal or pancreatic cancer:A critical update

Gastrointestinal toxicities(GIT), including oral mucositis,nausea and vomiting, and diarrhea, are common side effects of chemotherapy and targeted agents in patients with advanced colorectal cancer and pancreatic cancer. Being often underreported, it is still difficult to precisely establish their burden in terms of both patient's quality of life and cancer care costs. Moreover, with the use of more intensive upfront combination regimens, the frequency of these toxicities is rapidly growing with a potential negative effect also on patient's outcome, as a result of dose reductions, delays or even discontinuation of active treatments. Thus, identifying patients at higher risk of developing GIT as well as an optimal management are paramount in order to improve patient's compliance and outcome. After the description of the main treatment-induced GIT, we discuss the current knowledge on the pathophysiology of these side effects and comment the scales commonly used to assess and grade them. We then provide a critical update on GIT incidence based on the results of key randomized trials conducted in patients with metastatic colorectal cancer and advanced pancreatic cancer.

Acute and Sub-chronic Toxicity of Tetrandrine in Intravenously Exposed Female BALB/c Mice

Objective： To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine（TET） in female BALB/c mice. Methods： The median lethal dose（LD_（50）） of intravenously administered TET was calculated in mice using Dixon＇s up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET（30, 90 and 150 mg/kg） each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period. Result： LD_（50） was found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically significant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET（P〉0.05）. In the sub-acute toxicity study, no significant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group（P〉0.05）, however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions. Conclusions： The overall findings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.