Hemeida Ramadan A M, Mohafez Omar M
The Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch.
J Egypt Natl Canc Inst. 2008 Jun;20(2):141-8.
In the present study, we have addressed the ability of curcumin to suppress MTX-induced liver damage. Hepatotoxicity was induced by injection of a single dose of MTX (20mg/kg I.P.). MTX challenge induced liver damage that was well characterized histopathologically and biochemically. MTX increased relative liver/body weight ratio. Histologically, MTX produced fatty changes in hepatocytes and sinusoidal lining cells, mild necrosis and inflammation. Biochemically, the test battery entailed elevated activities of serum ALT and AST. Liver activities of superoxide dismutase (SOD), catalase (CAT) and level of reduced glutathione (GSH), were notably reduced, while lipid peroxidation, expressed as malondialdhyde (MDA) level was significantly increased. Administration of curcumin (100mg/kg, I.P.) once daily for 5 consecutive days after MTX challenge mitigated the injurious effects of MTX and ameliorated all the altered biochemical parameters. These results showed that administration of curcumin decreases MTX-induced liver damage probably via regulation of oxidant/anti-oxidant balance. In conclusion, the present study indicates that curcumin may be of therapeutic benefit against MTX-cytotoxicity.
在本研究中，我们探讨了姜黄素抑制甲氨蝶呤（MTX）诱导的肝损伤的能力。通过腹腔注射单剂量的MTX（20mg/kg）诱导肝毒性。MTX激发诱导的肝损伤在组织病理学和生物化学方面都有很好的特征。MTX增加了肝脏与体重的相对比值。组织学上，MTX导致肝细胞和肝血窦内皮细胞出现脂肪变性、轻度坏死和炎症。生物化学方面，检测项目包括血清谷丙转氨酶（ALT）和谷草转氨酶（AST）活性升高。肝脏中超氧化物歧化酶（SOD）、过氧化氢酶（CAT）的活性以及还原型谷胱甘肽（GSH）水平显著降低，而以丙二醛（MDA）水平表示的脂质过氧化作用则显著增加。在MTX激发后，连续5天每天腹腔注射一次姜黄素（100mg/kg）减轻了MTX的损伤作用，并改善了所有改变的生化参数。这些结果表明，姜黄素给药可能通过调节氧化/抗氧化平衡来减轻MTX诱导的肝损伤。总之，本研究表明姜黄素可能对MTX细胞毒性具有治疗益处。
