Laboratory of Cellular & Molecular Biology, School of Life Sciences, Jawaharlal Nehru University (JNU), New Delhi, India.
Interdisciplinary Brain Research Centre, Faculty of Medicine, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
J Biochem Mol Toxicol. 2018 Dec;32(12):e22226. doi: 10.1002/jbt.22226. Epub 2018 Sep 25.
The present study demonstrated the indomethacin (INDO) induced oxidative stress, hepatotoxicity, and genotoxicity in male Wistar rats. Animals were orally administrated INDO at doses of 0.302 and 0.605 (mg/kg b.w.) for 2 weeks. Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPO) activities/levels were measured in the liver, kidney, and brain tissues. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) activities, total bilirubin (TBIL) levels, and histopathological changes were determined in the liver tissues. Micronucleus frequency (micronucleus test) and DNA damage (comet assay) tests were performed in the bone marrow cells and leukocytes, respectively. Results show that INDO treatment decreased the GSH, SOD, and CAT levels/activities and increased the LPO, ALT, AST, ALP, and TBIL activities/levels. INDO induced significant hepatic injury and micronucleus and DNA damage. Thus, the current investigations confirm the oxidative stress, hepatotoxic, and genotoxic properties of INDO in the male Wistar rats.
本研究旨在探讨吲哚美辛(INDO)对雄性 Wistar 大鼠引起的氧化应激、肝毒性和遗传毒性。动物经口给予 INDO 剂量分别为 0.302 和 0.605(mg/kg b.w.),连续 2 周。检测肝脏、肾脏和脑组织中超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、过氧化氢酶(CAT)和脂质过氧化(LPO)的活性/水平;测定肝脏组织中天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)的活性,总胆红素(TBIL)的水平,以及组织病理学变化。进行骨髓细胞微核频率(微核试验)和白细胞 DNA 损伤(彗星试验)检测。结果表明,INDO 处理降低了 GSH、SOD 和 CAT 的水平/活性,增加了 LPO、ALT、AST、ALP 和 TBIL 的活性/水平。INDO 诱导了明显的肝损伤、微核和 DNA 损伤。因此,本研究证实了 INDO 在雄性 Wistar 大鼠中具有氧化应激、肝毒性和遗传毒性。