Department of Gastroenterology, Firat University Medical Faculty, Elazig, Turkey.
Hum Exp Toxicol. 2011 Jul;30(7):560-6. doi: 10.1177/0960327110374206. Epub 2010 Jun 9.
Tumor necrosis factor (TNF)-α antibodies have been shown to reduce liver damage in different models. We investigated the effects of infliximab (a TNF-α antibody) on liver damage in thioacetamide (TAA)-induced hepatotoxicity in rats. Group 1 (n = 8) was the control group. In group 2 (n = 8), the TAA group, the rats received 300 mg/kg intraperitoneal (ip) TAA daily for 2 days. In group 3 (n = 8), the TAA + Infliximab (INF) group, infliximab (5 mg/kg ip daily) was administered 48 hours before the first dose of TAA daily for 2 days and was maintained for 4 consecutive days. In group 4 (n = 8), the INF group, the rats received only ip infliximab (5 mg/kg) daily. Livers were excised for histopathological and biochemical tests (thiobarbituric-acid-reactive substances [TBARS], and myeloperoxidase [MPO]). Serum ammonia, aspartate transaminase (AST), alanine transaminase (ALT), TNF-α, liver TBARS and MPO levels, and liver necrosis and inflammation scores in the TAA group were significantly higher than in the control and INF groups (all p < 0.01). All parameters except AST were not significantly different between TAA and TAA + INF. In conclusion, our results suggest that oxidative stress plays an important role in TAA-induced hepatotoxicity, and infliximab does not improve oxidative liver damage.
肿瘤坏死因子 (TNF)-α 抗体已被证明可减少不同模型中的肝损伤。我们研究了英夫利昔单抗（一种 TNF-α 抗体）对硫代乙酰胺 (TAA) 诱导的大鼠肝毒性中肝损伤的影响。第 1 组（n = 8）为对照组。第 2 组（n = 8）为 TAA 组，大鼠每天腹腔内（ip）给予 300 mg/kg TAA 共 2 天。第 3 组（n = 8）为 TAA+Infliximab（INF）组，在第 1 天 TAA 前 48 小时给予 Infliximab（5mg/kg ip 每天），并连续 4 天维持。第 4 组（n = 8）为 INF 组，大鼠每天仅腹腔内给予 Infliximab（5mg/kg）。为组织病理学和生化测试（硫代巴比妥酸反应物质 [TBARS] 和髓过氧化物酶 [MPO]）切除肝脏。TAA 组血清氨、天冬氨酸转氨酶 (AST)、丙氨酸转氨酶 (ALT)、TNF-α、肝 TBARS 和 MPO 水平以及肝坏死和炎症评分明显高于对照组和 INF 组（均 p < 0.01）。除 AST 外，TAA 和 TAA + INF 之间的所有参数均无显着差异。总之，我们的结果表明氧化应激在 TAA 诱导的肝毒性中起重要作用，而英夫利昔单抗不能改善氧化肝损伤。
