Acemetacin Induces Antioxidant Dysregulation, While Mefenamic Acid has a Hepatoprotective Effect Against Ischemia-Reperfusion Injury

Background and Objective: Liver graft rejection is the most common complication after transplantation, the key factor associated with graft rejection is ischemia-reperfusion (IR) injury. Inhibitors of cyclooxygenase (COX) have a protective effect against IR injury in several organs, suggesting a role for COX in the modulation of IR injury in these organs. Hence, this study aimed to determine whether the administration of either ACE or MFA has a hepatoprotective effect against IR injury in Wistar rats. Materials and Methods: Twenty-four female Wistar rats were divided into four groups (n = 6): Sham (SH), IR, mefenamic acid (MFA)+IR and acemetacin (ACE)+IR. Serum ALT, AST, LDH, ALP, glucose and total bilirubin were assessed. The concentrations of IL-1 beta, IL-6, TNF, malondialdehyde, superoxide dismutase and glutathione peroxidase were measured in liver tissue as well as the expression of Sod1, Gpx1, Mpo, I11-B, Rela (rat nomenclature) and determined by RT-qPCR. Sections of liver tissue were evaluated histologically, evaluating the severity of necrosis, sinusoidal congestion and cytoplasmatic vacuolization. Results: The MFA and ACE decreased the serum activity of liver enzymes (AST, ALT and LDH) after the induction of liver injury. The MFA demonstrated a hepatoprotective effect but not ACE, possibly due to its role in the deregulation of the antioxidant system demonstrated by a decreased expression of Sod and Gpx1 and increased IL-1 beta levels. Conclusion: The MFA has a hepatoprotective effect against IR damage. The hepatoprotective effect of ACE was discarded.