Alantolactone

Abstract: Background: Doxorubicin (DOX) is a widely prescribed chemotherapeutic agent, but its therapeutic use is frequently restricted due to its harmful effects on the kidneys.This research evaluated the nephroprotective properties of alantolactone (ATL), a naturally sourced sesquiterpene lactone, in a rat model of DOX-induced kidney injury, along with computational anal. of its mol. binding interactions.Methods and results: Male Wistar rats were randomly assigned to five groups: Control, ATL (10), DOX, ATL (5) + DOX, and ATL (10) + DOX.The Control and DOX groups received 0.5% sodium CM-cellulose orally for 18 days, whereas ATL was given orally at 10 mg/kg in the ATL-alone group.ATL was also administered orally at 5 or 10 mg/kg in the resp. co-treatment groups.On day 17, DOX (20 mg/kg, i.p.) was administered to the DOX and co-treated animals.Renal function was assessed through serum biomarkers; oxidative stress (MDA, SOD, CAT), inflammatory markers (IL-6, TNF-α, NF-κB p65), and apoptosis-related genes (Bax, Bcl-2) were evaluated using biochem. methods, immunohistochem. and qRT-PCR.Expression of Nrf2 and HO-1 was analyzed, and mol. docking assessed interactions of ATL and DOX with Keap1 and TNF-α.ATL co-administration significantly alleviated DOX-induced renal impairment by reducing oxidative stress, inflammation, and apoptotic responses, while enhancing Nrf2 and HO-1 expression.Docking studies demonstrated strong binding affinity of ATL to Keap1 and TNF-α.Conclusion: ATL confers nephroprotection against DOX-induced toxicity, potentially through its antioxidant, anti-inflammatory, and anti-apoptotic effects linked to Nrf2 and HO-1 activation.Graphical Abstract: