Benzo[a]pyrene-induced nephrotoxicity driven by intricate interplay between autophagy and apoptosis in Channa punctata: Unravelling insights of c-myc and atg5

• B[a]P exposure induces oxidative stress-mediated Nephrotoxicity in Channa punctata . • cyp1a1 and GST induction indicate activation of biotransformation pathways. • DNA damage and apoptosis confirmed by elevated micronuclei and apoptotic cells. • c-myc downregulation and atg5 upregulation validate autophagy–apoptosis crosstalk. • PCA links oxidative stress, genotoxicity, apoptosis, and histopathological changes. The present study provides a concrete toxicogenomic validation of the autophagy-apoptosis interplay in fish kidneys under Benzo[a]pyrene (B[a]P) stress, thereby enhancing the understanding of cell death mechanisms in aquatic organisms. Channa punctata were divided into four groups: control, solvent control, and two treatment groups exposed to sub-lethal B[a]P concentrations (0.448 and 0.896 mg/L) for 45 days. Renal toxicity was evaluated using biochemical assays, histopathology, and molecular markers. Exposure to B[a]P led to significant oxidative stress, as evidenced by elevated reactive oxygen species (ROS) and disruption of antioxidant defenses [superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione (GSH)]. Induction of cytochrome P4501A1 ( cyp1a1 ) and glutathione-S-transferase (GST) reflected the activation of detoxification pathways. DNA damage was confirmed by increased micronucleus (MN) frequency and apoptotic cell (AC) counts, which were consistent with altered gene expression: upregulation of smac/diablo, atg-5, caspase-8 , and caspase-3 , alongside downregulation of c-myc and xiap . These findings suggest concurrent activation of autophagy and apoptosis. Biochemical indicators of renal dysfunction (blood urea nitrogen and creatinine) and histological changes, including condensed nuclei, tubule degeneration, cavity reduction in renal tubules, and apoptosis, further validated nephrotoxicity. Protein–protein interaction analysis revealed clusters functionally linked to autophagy, apoptosis, and xenobiotic metabolism, supporting a mechanistic interplay. In conclusion, B[a]P acts as a potent nephrotoxicant in fish by initiating oxidative stress and triggering autophagy–apoptosis crosstalk. This study provides new insights into pollutant-induced cell death mechanisms in aquatic vertebrates and strengthens the understanding of molecular responses to environmental carcinogens.