protective role of feselol against acetaminophen-induced nephrotoxicity in mice: modulation of oxidative stress, apoptotic, and inflammatory pathways

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.