Alteration of endoplasmic reticulum stress, inflammation and anti-oxidative status in cyclophosphamide-damaged liver of Nile tilapia (Oreochromis niloticus)

文献类型： 外文期刊

第一作者： Cao, Liping

作者： Cao, Liping;Du, Jinliang;Nie, Zhijuan;Jia, Rui;Yin, Guojun;Xu, Pao;Ding, Weidong;Xu, Gangchun

作者机构：

关键词： Cyclophosphamide; Oreochromis niloticus; Oxidative stress; Inflammation; Endoplasmic reticulum stress

期刊名称：COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY （ 影响因子：4.52； 五年影响因子：4.203 ）

ISSN： 1532-0456

年卷期： 2022 年 254 卷

页码：

收录情况： SCI

摘要： Cyclophosphamide (CTX) is a common immunosuppressant, and it can also results in liver injury in human and animals. In this study, the CTX-induced liver injury mechanism in tilapia (Oreochromis niloticus) was investigated by studying alteration of endoplasmic reticulum stress (ERS), inflammation and anti-oxidative status. Tilapia was intraperitoneally injected CTX at the doses of 10, 25, 50, 75 and 100 mg.kg(-1), and the blood and liver tissues were collected. The results showed that CTX administration had a significant cytotoxicity on hepatocytes, and increased the liver index. The extensive vacuolar degeneration, unclear cell outline and other histological lesions were also observed. CTX administration markedly decreased the antioxidant ability and enhanced lipid perox-idation in liver. Furthermore, qPCR data showed that CTX administration at 50-100 mg.kg(-1) up-regulated gene expressions of cyp1a, cyp2k1 and cyp3a, and inflammatory response-related genes including rel, relb, nf kappa b1, il-6, il -8, il-10 and tnf-alpha. CTX significantly promoted the mRNA levels of ERS-related genes (eif2 alpha, crt, parp1, grp78, ire1, xbp1s and chop) in a dose dependent manner. Additionally, CTX injection at 75-100 mg.kg(-1) could down-regulate gene expressions of anti-oxidative status including nrf2, ucp2, ho-1, gpx3, gst alpha and cat. Overall results suggested CTX injection induced liver damage which was related to the cytotoxic effect on hepatocytes, decrease of antioxidant capacity, inflammatory response and ERS.

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