Wu Yan-Ling, Piao Dong-Ming, Han Xue-Hua, Nan Ji-Xing
Key Laboratory of Organism Functional Factors of the Changbai Mountain, College of Pharmacy, Yanbian University, Jilin Province, China.
Biol Pharm Bull. 2008 Aug;31(8):1523-9. doi: 10.1248/bpb.31.1523.
The protective effect of salidroside (SDS) isolated from Rhodiola sachalinensis A. BOR. (Crassulaceae), was investigated in acetaminophen (APAP)-induced hepatic toxicity mouse model in comparison to N-acetylcysteine (NAC). Drug-induced hepatotoxicity was induced by an intraperitoneal (i.p.) injection of 300 mg/kg (sub-lethal dose) of APAP. SDS was given orally to mice at a dose of 50 or 100 mg/kg 2 h before the APAP administration in parallel with NAC. Mice were sacrificed 12 h after the APAP injection to determine aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-alpha (TNF-alpha) levels in serum and glutathione (GSH) depletion, malondialdehyde (MDA) accumulation, and caspase-3 expression in liver tissues. SDS significantly protected APAP-induced hepatotoxicity for SDS improved mouse survival rates better than NAC against a lethal dose of APAP and significantly blocked not only APAP-induced increases of AST, ALT, and TNF-alpha but also APAP-induced GSH depletion and MDA accumulation. Histopathological and immunohistochemical analyses also demonstrated that SDS could reduce the appearance of necrosis regions as well as caspase-3 and hypoxia inducible factor-1alpha (HIF-1alpha) expression in liver tissue. Our results indicated that SDS protected liver tissue from the APAP-induced oxidative damage via preventing or alleviating intracellular GSH depletion and oxidation damage, which suggested that SDS would be a potential antidote against APAP-induced hepatotoxicity.
与N-乙酰半胱氨酸（NAC）相比，研究了从红景天（景天科）中分离出的红景天苷（SDS）对乙酰氨基酚（APAP）诱导的肝毒性小鼠模型的保护作用。通过腹腔注射300mg/kg（亚致死剂量）的APAP诱导药物性肝毒性。在给予APAP前2小时，将SDS以50或100mg/kg的剂量口服给予小鼠，同时给予NAC。在注射APAP后12小时处死小鼠，以测定血清中的天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和肿瘤坏死因子-α（TNF-α）水平，以及肝组织中的谷胱甘肽（GSH）消耗、丙二醛（MDA）积累和半胱天冬酶-3表达。SDS显著保护了APAP诱导的肝毒性，因为与NAC相比，SDS对致死剂量的APAP提高了小鼠存活率，并且不仅显著阻断了APAP诱导的AST、ALT和TNF-α升高，还阻断了APAP诱导的GSH消耗和MDA积累。组织病理学和免疫组织化学分析还表明，SDS可以减少肝组织中坏死区域的出现以及半胱天冬酶-3和缺氧诱导因子-1α（HIF-1α）的表达。我们的结果表明，SDS通过预防或减轻细胞内GSH消耗和氧化损伤来保护肝组织免受APAP诱导的氧化损伤，这表明SDS可能是一种对抗APAP诱导的肝毒性的潜在解毒剂。
