Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.
J Pharm Pharmacol. 2012 Feb;64(2):259-67. doi: 10.1111/j.2042-7158.2011.01393.x. Epub 2011 Dec 7.
This study evaluated the protective effects of gentisic acid (GA) against genotoxicity and hepatotoxicity induced by cyclophosphamide (CP) in Swiss albino mice.
Mice were pretreated with GA orally at doses of 50 and 100 mg/kg for 14 consecutive days before the administration of a single intraperitoneal dose of 50 mg/kg CP. The ameliorative effect of GA on genotoxicity was studied using the in-vivo bone marrow micronuclei induction test, DNA integrity and alkaline unwinding assay. The activity of various oxidative stress enzymes were estimated in hepatic tissue.
A single intraperitoneal administration of CP in mice increased the malondialdehyde level, depleted the glutathione content and antioxidant enzyme activity (glutathione peroxidase, glutathione reductase, catalase and quinone reductase), and induced DNA strand breaks and micronuclei induction. Oral pretreatment with GA at both doses caused a significant reduction in malondialdehyde and glutathione levels, restoration of antioxidant enzyme activity, reduction in micronuclei formation and DNA fragmentation. Serum toxicity marker enzymes such as aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were increased after CP treatment but restored in GA pretreated groups.
The results support the protective effect of GA against CP induced genotoxicity and hepatotoxicity.
本研究旨在评估没食子酸（GA）对环磷酰胺（CP）诱导的瑞士白化小鼠遗传毒性和肝毒性的保护作用。
小鼠连续 14 天每天经口给予 GA（剂量分别为 50 和 100mg/kg）预处理，然后单次腹腔内给予 50mg/kg CP。采用体内骨髓微核诱导试验、DNA 完整性和碱性解旋试验研究 GA 对遗传毒性的改善作用。在肝组织中估计各种氧化应激酶的活性。
CP 单次腹腔内给药可增加丙二醛水平，耗尽谷胱甘肽含量和抗氧化酶活性（谷胱甘肽过氧化物酶、谷胱甘肽还原酶、过氧化氢酶和醌还原酶），并诱导 DNA 链断裂和微核形成。GA 在两个剂量下的口服预处理均可显著降低丙二醛和谷胱甘肽水平，恢复抗氧化酶活性，减少微核形成和 DNA 片段化。CP 处理后血清毒性标志物酶（天冬氨酸氨基转移酶、丙氨酸氨基转移酶和乳酸脱氢酶）升高，但在 GA 预处理组中得到恢复。
这些结果支持 GA 对 CP 诱导的遗传毒性和肝毒性的保护作用。
