Hydrogen Sulfide Protects Mice Against Cisplatin-induced Liver Damage

AIM:To study the effects of hydrogen sulfide on cisplatin induced liver injury and its molecular mechanism of hepatocyte protection.METHODS:We used NaHS as the hydrogen sulfide donor.Mice were intraperitoneally injected daily with 5.6mg/kg,and cisplatin(DDP)liver damage model was prepared by intraperitoneal injection of cisplatin(12mg/kg)at fourth days,and NaHS was continuously given for another 4 days.The liver ALT level was detected by the kit,and the oxidative stress indexes such as SOD,GSH,CAT and iNOS were detected by quantitative PCR,and the inflammatory factors such as IL-1?,F4/80,IL-4 and IL-10 were detected by quantitative PCR.The morphological changes of liver tissues were observed by HE staining,and the intracellular reactive oxygen species(ROS)were detected by fluorescence probe and flow cytometry.TUNEL staining was used to observe the cell apoptosis.RESULTS:Cisplatin can significantly reduce the weight of liver,while NaHS treatment significantly alleviated the decrease of liver weightand inhibited the increase of ALT caused by cisplatin administration.Cisplatin significantly inhibited the expression of antioxidant enzyme CAT,and increased the expression of iNOS,which promoted oxidative damage.After NaHS treatment,it could significantly promote the expression of CAT enzyme,inhibited the expression of iNOS,and significantly increased the expression of antioxidant enzyme SOD;TUNEL staining results showed that cisplatin could significantly induce hepatocyte decay.NaHS could inhibit cisplatin induced hepatocyte apoptosis,and ROS flow cytometry showed that cisplatin could significantly increase the level of ROS in L02 of liver cells,while NaHS pretreatment could significantly inhibit the level of ROS,and further we found that cisplatin could significantly promote the mRNA expression of the macrophage cell marker of the liver,F4/80,and NaHS energy.The expression of F4/80 was significantly inhibited,and NaHS could significantly inhibit the expression of mRNA of IL-1? in the liver of cisplatin,and the expression of IL-4 and IL-10 mRNA in the liver of cisplatin treatment group.CONCLUSION:Hydrogen sulfide donor NaHS can significantly inhibit the liver damage caused by cisplatin,the main mechanism is that NaHS plays the protective role of liver cells by alleviating oxidative stress and inflammatory response.