Hepatic Responses to Acetaminophen Challenge in SelenBP1-Deficient Mice

Background/Objectives: Selenium-binding protein 1 (SelenBP1) has been identified as a target protein for covalent binding of N-acetyl-p-benzoquinone imine (NAPQI), the reactive metabolite of acetaminophen (APAP). However, its contribution to APAP-induced hepatotoxicity remains unclear. In the present study, we evaluated the hepatic response to APAP challenge in male SelenBP1-deficient mice. Methods: Male SelenBP1(−/−) and SelenBP1(+/+) mice were fasted for 20 h and treated with APAP (200 mg/kg, i.p.). Hepatic SelenBP1 and SelenBP2 expression levels were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. Notably, the antibody could not discriminate between the SelenBP1 and SelenBP2 bands in wild-type male liver samples; therefore, Western blot data represent the combined total of SelenBP1 and SelenBP2 proteins. Liver injury was assessed using histopathology and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Results: Hepatic SelenBP1 mRNA levels were markedly decreased in SelenBP1(+/+) mice following APAP treatment, whereas SelenBP2 mRNA expression was not further suppressed by APAP in either genotype. Histopathological examination revealed comparable centrilobular necrosis in both genotypes, and no significant differences were observed in serum ALT or AST activities. These findings indicated that there were no statistically significant differences in the measured liver injury parameters between wild-type and SelenBP1 knockout male mice. In addition, fasting induced distinct changes in total hepatic SelenBP1/SelenBP2 protein abundance in wild-type versus SelenBP1-deficient mice. Conclusions: No statistically significant differences in fasting-enhanced APAP-induced liver injury were observed between wild-type and SelenBP1 knockout male mice. Altered total hepatic SelenBP1/SelenBP2 protein levels in SelenBP1-deficient mice were an observational finding; a potential compensatory mechanism remains an unverified hypothesis requiring further investigation.