Probiotic Bacillus subtilis attenuates cisplatin-induced multi-organ toxicity via redox modulation and anti-apoptotic mechanisms: Evidence from a preclinical probiotic intervention study

Cisplatin, a widely used chemotherapeutic agent, is limited by dose-dependent multi-organ toxicity. Probiotic interventions have recently emerged as promising strategies to alleviate such adverse effects through antioxidative and cytoprotective mechanisms. This preclinical study evaluated the protective effects of the spore-forming probiotic Bacillus subtilis against cisplatin-induced toxicity in female Wistar rats. Animals were assigned to control, cisplatin-only, probiotic-only, and cisplatin + probiotic groups. Biochemical indices, antioxidant enzyme activities, oxidative stress markers, and histopathological changes were systematically evaluated to determine the therapeutic efficacy of B. subtilis . Cisplatin disrupted hematological indices, altered carbohydrate and lipid metabolism, elevated oxidative stress markers (ROS, MDA), and increased DNA damage (8-OHdG) and apoptosis (caspase-3). B. subtilis supplementation restored antioxidant enzyme activities (CAT, SOD, GPx), reduced oxidative and apoptotic damage, and preserved tissue structure. These protective effects are consistent with modulation of the Nrf2/Keap1 and NF-κB pathways, suggesting enhancement of endogenous antioxidant defenses and suppression of pro-apoptotic signaling. B. subtilis demonstrates potential as a safe, gut-resilient probiotic adjunct to chemotherapy, capable of mitigating systemic toxicity through redox regulation and cytoprotective mechanisms. These findings support further mechanistic and translational studies to validate probiotic-based microecological strategies in oncology care. • Bacillus subtilis reduced cisplatin-induced oxidative stress and tissue damage in rats. • Protection linked to Nrf2/Keap1 activation and NF-κB/p53 pathway suppression. • Spore-forming trait supports gut–organ axis modulation during chemotherapy. • Promising microbiome-based adjunct to improve cisplatin safety in cancer care.