摘要
目的观察新型铂类化合物LLC-0601与舒铂对SD大鼠的肝毒性,探讨其可能的毒性作用机制。方法 雄性SD大鼠尾静脉iv给予顺铂2mg.kg-1(阳性对照)、舒铂40mg.kg-1、LLC-060140和70mg.kg-1,连续2d,间隔5d,共6次,末次给药后恢复期28d,观察动物一般状况,并于给药末期和恢复28d后检测血清谷丙转氨酶(GPT),谷草转氨酶(GOT),碱性磷酸酶(ALP),总蛋白(TP),白蛋白(ALB)和总胆红素(T-Bil),肝质量与系数,组织匀浆谷胱甘肽过氧化物酶(GSH-Px),超氧化物歧化酶(T-SOD),微量丙二醛(MDA)及光学显微镜进行病理组织学检查。结果与正常对照组相比,LLC-060140mg.kg-1组各项检测指标未见明显异常,其余给药组动物均出现精神差、少食、少动、竖毛、毛发无光泽以及体质量下降;给药末期血清生化检测舒铂组GPT升高,TP和ALB降低(P<0.05);与正常对照组相比,顺铂、舒铂和LLC-060170mg.kg-1组肝质量明显降低(P<0.05),顺铂和舒铂组肝系数明显降低(P<0.05);顺铂、舒铂和LLC-060170mg.kg-1组肝组织匀浆中GSH-Px和T-SOD降低,各给药组MDA均升高(P<0.05);顺铂、舒铂和LLC-060170mg.kg-1组肝病理组织学均出现不同程度肝细胞点灶状坏死,肝窦内淋巴细胞浸润,以舒铂组病变程度最重。恢复期顺铂组病理组织学病变较给药末期重,出现延迟性毒性反应,其余各给药组各项检测指标均基本恢复。结论顺铂、舒铂和LLC-0601均可引起大鼠肝损伤,其机制与药物引起的组织过氧化损伤有关。
OBJECTIVE To investigate the hepatotoxicity of heptaplatin and LLC-0601 in SD rats,and to explore the toxic mechanisms.METHODS Rats were respectively injected with cisplatin 2 mg·kg-1(positive control),heptaplatin 40 mg·kg-1 and LLC-0601 40 and 70 mg·kg-1,once a day,for 2 d,and then an inteval for 5 d,all 3 courses for 6 injections,and then rats restored for 28 d.After the last 24 h after administration and after restoration 28 d,the rats were inspected for their general condition.Serum biochemistry indices glutamic pyruvic transaminase(GPT),glutamic oxaloacetic transaminase(GOT),alkaline phosphatase(ALP),total protein(TP),albumin(ALB) and total bilirubin(T-Bil) were detected.Liver mass and coefficients were detected.The activity of glutathione peroxidase(GSH-Px),total superoxide dismutase(T-SOD) and malondialdehyde(MDA) was examined and liver histopathology was observed.RESULTS Compared with normal control group,rats in treated groups except LLC-0601 70 mg·kg-1 appeared to be dispirited,and mat,food intake decreased,significant vertical hair phenomena,with a reduction of activity.GPT was higher,but TP and ALB were lower in heptaplatin group(P0.05).Compared with normal control group,liver mass and organ coefficients,GSH-Px and T-SOD were lower in the drug-treated groups(P0.05).While MDA was significantly higher(P0.05).Liver tissue in cisplatin,heptapletin and LLC-0601 70 mg·kg-1 groups showed focal necrosis and sinusoidal lymphocytic infiltration of liver cells.After 28 d restoration all indices returned to normal except cisplatin group.CONCLUSION Heptaplatin and LLC-0601 can induce liver damage and the mechanism may be related to their oxidative damage.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2011年第4期369-374,共6页
Chinese Journal of Pharmacology and Toxicology
基金
云南省教育厅科学研究基金项目资助(09J0055)~~