Sufentanil preconditioning reduces hepatic ischemia-reperfusion injury in rats by regulating ferroptosis through ATF3

To examine the correlation between the therapeutic efficacy of sufentanil preconditioning on hepatic ischemia-reperfusion injury (HIRI)-induced ferroptosis and the activation of activating transcription factor 3 (ATF3), as well as to elucidate the underlying mechanisms involved. Eighteen Sprague-Dawley (SD) male rats were randomly assigned to three groups: a sham operation group, an ischemia-reperfusion injury group, and a sufentanil pretreatment group. Serum transaminase levels, specifically alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were measured to assess liver function. Liver injury was evaluated using hematoxylin and eosin staining. Ferroptosis was assessed by measuring iron content, glutathione peroxidase 4 (GPX4) expression levels, and mitochondrial morphological changes in hepatocytes. The relationship between the protective effects of sufentanil and ATF3 was investigated through immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). Sufentanil pretreatment was found to ameliorate liver tissue damage, attenuate the inflammatory response, and mitigate ferroptosis in the context of HIRI. Furthermore, Sufentanil enhanced the expression levels of ATF3 while concurrently reducing iron content within liver tissue. Sufentanil preconditioning may mitigate ferroptosis associated with HIRI through the upregulation of ATF3 expression. This protective mechanism may be linked to a concomitant reduction in iron levels.