Abstract
Doxorubicin (DOX)-induced cardiotoxicity converges on oxidative-nitrosative stress, TLR4/NF-κB-driven inflammation, and caspase-3-mediated apoptosis, and remains a major dose-limiting complication of anthracycline therapy. Dexpanthenol (DEX), a coenzyme A precursor, has shown anti-oxidative, anti-inflammatory, and anti-apoptotic activity in diverse organ-injury models, but its cardioprotective potential against DOX has not been systematically evaluated. The present study aimed to investigate the protective effects of DEX against DOX-induced cardiotoxicity in Wistar rats. Twenty-eight male Wistar rats were randomly allocated to four groups (n = 7): Control, DOX (single 25 mg/kg i.p. on day 1), DOX + DEX (DOX on day 1 followed by 500 mg/kg/day DEX for eight days), and DEX (500 mg/kg/day for eight days). TLR4, NF-κB p65, TNF-α, MDA, SOD, and GSH were quantified by ELISA in both serum and cardiac tissue; caspase-3 and GFAP were quantified in cardiac tissue. Cardiac TAS, TOS, OSI, NO, and iNOS were also measured. Myocardial sections were graded for seven histopathological parameters by a blinded pathologist. DOX produced a robust cardiotoxic phenotype, with elevations in inflammatory, oxidative, nitrosative, and apoptotic markers, depletion of antioxidant defenses, and marked histopathological injury. Co-administration of DEX attenuated TLR4/NF-κB/TNF-α signaling in both compartments, reduced caspase-3 and GFAP, normalized TAS and OSI, and significantly improved five of seven histopathological parameters after multiplicity adjustment. Protection was selective: cardiac SOD, GSH, NO, and total oxidant status were only partially restored, and inflammatory cell infiltration was unchanged. DEX exerts a partial but mechanistically coherent cardioprotective effect against DOX-induced cardiotoxicity, chiefly through attenuation of TLR4/NF-κB-driven inflammation and caspase-3 signaling. These findings support its evaluation as a multi-target adjunct in cardio-oncology.