Protective Role of Feselol Against Acetaminophen-Induced Nephrotoxicity in Mice: Modulation of Oxidative Stress, Apoptotic, and Inflammatory Pathways

Abstract

Background: Kidney damage from acetaminophen can lead to acute or chronic kidney failure. Objectives: This study investigated the protective effect of feselol, a sesquiterpene coumarin from the Ferula genus, against acetaminophen-induced nephrotoxicity in mice. Methods: Forty-two adult male mice were randomly divided into seven groups (n = 6) and studied over three days. Acetaminophen-induced kidney damage was treated with feselol or N-acetylcysteine (NAC) as a reference drug. Biochemical markers of oxidative stress [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)] were measured spectrophotometrically using commercial kits. Gene expression of apoptotic markers (Bax, caspase-3, Bcl-2) and levels of inflammatory cytokines [TNF-α, IL-1β, Interleukin-10 (IL-10)] were assessed using the real-time (RT)-PCR method. Results: Acetaminophen administration caused significant oxidative stress in the kidney, which was accompanied by an increase in MDA levels and a decrease in the activities of antioxidant enzymes SOD, CAT, and GPx. Co-administration of feselol, especially at a dose of 50 mg/kg, reduced MDA and increased CAT and GPx. Apoptosis analysis showed that acetaminophen increased the expression of caspase-3 and Bax and decreased the expression of Bcl-2 and the Bcl-2/Bax ratio. Feselol decreased the expression of caspase-3 and Bax and increased the expression of Bcl-2 and the Bcl-2/Bax ratio, and at a higher dose had a similar effect to NAC, although NAC was more effective in normalizing Bcl-2. Acetaminophen also increased TNF-α and IL-1β and decreased IL-10. Feselol improved these changes, while NAC had a stronger effect in reducing IL-1β. Tween administration had no effect, and the feselol alone group showed no signs of oxidative damage, apoptosis, or inflammation. Conclusions: In this study, feselol showed potential antioxidant, anti-apoptotic, and anti-inflammatory effects and may have protective effects against acetaminophen-induced renal injury. Its protective efficacy at a dose of 50 mg/kg was similar to that of NAC, although NAC performed more potently in some indices. Therefore, feselol could be investigated as a natural compound with therapeutic potential, as an alternative or supplement to NAC in preventing and reducing acetaminophen-induced renal injury in future preclinical studies.