Protective Effect Of Taurine On Liver Injury Induced By Cyclophosphamide In Mice

Cyclophosphamide(CP)is a broad-spectrum antitumour drug and the hepatotoxicity caused by its treatment has limited its use.A large body of research data suggests that taurine(Tau)is effective against inflammation,oxidative stress and apoptosis.However,it is unclear whether Tau can attenuate or protect against CP-induced liver injury.Therefore,this study analysed the protective effects of Tau on CP-induced liver injury in mice based on the establishment of a CP-induced liver injury model,and the following main findings were obtained:1.The key enzyme for Tau synthesis,CSD,Tau transporter TauT and Tau content were examined using immunohistochemistry,HPLC and Western blot techniques.The results showed that CSD and TauT were expressed in the liver;the liver Tau content increased 1.04fold in the CP group,and the CSD protein expression was down-regulated by 43.4%and the transporter protein TauT expression was up-regulated by 33.8%,suggesting that CP injection reduced the ability of the liver to synthesize Tau,but increased the transporter ability.2.Histopathology,liver function,pro-inflammatory cytokines and oxidative stressrelated enzymes were determined in mice using paraffin sections,HE staining,biochemical assays,Real-time PCR and ELISA.The results showed that the mice in the CP group had reduced body weight and liver coefficients by 14.9%;CP treatment resulted in a large accumulation of inflammatory cells in the liver,whereas the number of inflammatory cells in Tau-supplemented liver was significantly reduced;the CP group had a significant decrease in glutathione aminotransferase(AST)and alanine aminotransferase(AST).(AST)and Alanine aminotransferase(ALT)levels were upregulated by 41.4%and 62.3%,respectively,while Tau significantly suppressed the elevated levels of both;and CP treatment resulted in significantly higher expression levels of MDA and pro-inflammatory cytokines IL-1β,IL-6 and TNF-α,upregulated by 59.5%,73.5%,175.8%and 104.6%,respectively;In addition,Tau treatment reversed the decrease of antioxidant enzymes CAT and SOD activity caused by CP.The above results suggest that Tau may reduce CP-induced liver injury by inhibiting the production of oxidative stress and pro-inflammatory cytokines.3.p65 and IKBα,key factors of the NF-κB pathway,and Bax and Bcl-2,major related proteins of the mitochondrial apoptosis pathway,were examined in mouse liver using Western blot.The results showed that CP treatment led to increased phosphorylation of p65,while Tau inhibited its phosphorylation and the inhibitory protein of p65,IKBα,showed the opposite trend;the Bax/Bcl-2 ratio in the CP group was significantly up-regulated by 134.5%compared to the control group,while Tau reversed the up-regulation trend.These results suggested that Tau could alleviate CP-induced liver injury by inhibiting the NF-κB pathway as well as the mitochondrial apoptosis pathway.By culturing human hepatocellular carcinoma cells(HepG2)in vitro and treating them with 4-hydroperoxycyclophosphamide,the levels of reactive oxygen species,inflammatory cytokines and apoptosis-related proteins were examined in each group and were consistent with the in vivo results.In summary,Tau alleviates CP-induced liver injury by inhibiting inflammation,oxidative stress and apoptosis by inhibiting the NF-κB pathway and the mitochondrial apoptotic pathway.The experimental results will provide a new therapeutic basis for ameliorating the toxic effects of CP in clinical practice.