Exploring the protective impacts of Rhodiola rosea extract against vancomycin-induced hepatic and renal toxicity through the activation of Nrf2/HO-1 and MAPK kinases, inhibition of NF-κB and TGF-β1 signaling pathways, role of apoptosis and inflammation associated-markers

(RHO), a medicinal plant with potent antioxidant and anti-inflammatory activities, was evaluated for its protective effects against vancomycin (VMC)-induced hepatorenal toxicity in rats. Rats received VMC for 7 consecutive days, while the treatment group was pretreated with RHO 1 h before each VMC administration. VMC induced marked liver and kidney dysfunction, oxidative stress, inflammation, and apoptosis, as evidenced by altered hepatorenal biomarkers, increased lipid peroxidation, depletion of antioxidant defenses, dysregulated cytokine levels, and upregulation of injury-, inflammatory-, and apoptotic-related genes. RHO pretreatment significantly attenuated these alterations, restored antioxidant status, enhanced Nrf2/HO-1 signaling, suppressed inflammatory and apoptotic pathways, and improved the expression of renal integrity markers. Histological and immunohistochemical findings further confirmed the protective effects of RHO through modulation of Bcl-2 and caspase-3 expression. These findings demonstrate that RHO effectively mitigates VMC-induced hepatorenal injury by regulating oxidative stress, inflammation, apoptosis, and related signaling pathways.