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

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.

Automated summary

This study investigated the mechanism of CTX-induced liver injury in tilapia by studying the changes in endoplasmic reticulum stress, inflammation, and antioxidant status. The results showed that CTX administration caused cytotoxicity on hepatocytes, increased liver index, and histological lesions. CTX also decreased antioxidant ability, up-regulated inflammatory response-related genes, and promoted ERS-related gene expression. Furthermore, CTX injection down-regulated gene expressions related to antioxidative status. Overall, these findings suggest that CTX injection induces liver damage through cytotoxicity, reduced antioxidant capacity, inflammation, and endoplasmic reticulum stress.