Effects of Stem Cell Factor on Activity of Glutathione S-transferase and Recovery from Acetaminophen-induced Hepatotoxicity in Mice

Objective: Acetaminophen (APAP) overdose causes acute liver injuries. Studies show that stem cell factor (SCF) and its receptor, c-Kit, enhance liver recovery from APAP-induced injuries in mice. In this study we explore the effect of SCF on activity of glutathione S-transferase (GSTs) enzymes which are considered to be important in APAP metabolism. Methods: We divided ۴۵ Balb/c mice into three groups. Within each group there were three sub-groups of five mice per subgroup. The groups included: ۱. APAP (۳۰۰ mg/kg B.W., i.p.); ۲. SCF (۴۰ µg/kg B.W., i.p.) given.۳۰ minutes after APAP (۳۰۰ mg/kg B.W., i.p.), and ۳.control mice treated with normal saline. The mice were sacrificed at ۱, ۱۲ and ۲۴ hours, respectively. Hepatotoxicity was evaluated in the ۲۴ hour group by histopathology and assessment of biochemical serum markers (ALT and AST). We assessed the levels of SCF receptor (c-Kit) protein and GST enzyme activities in the liver tissues.  Results: Hepatotoxicity was induced by APAP (۳۰۰ mg/kg, B.W) as evident by both histopathological observations and a significant (p<۰.۰۵) increase in serum ALT and AST levels, which were reversed by SCF administered post-APAP. SCF administration after APAP administration significantly increased GSTs enzyme activity levels by ۲۴ hours, however it led to a significant decrease in c-Kit protein level compared to the control and APAP groups. Conclusion: Our data suggest that SCF binding to its receptor (c-Kit) on liver cells may attenuate APAP-induced liver injuries by increasing GST activities in the livers of mice.

کلیدواژه ها:

Stem Cell Factor ، Acetaminophen ، Hepatotoxicity ، GSTs ، عامل سلول بنیادی ، استامینوفن ، سمیت کبدی ، گلوتاتیون-اس- ترانسفرازها