Dietary chitosan mitigates hepatic and renal dysfunction in 1,2-dimethylhydrazine-induced colorectal cancer in wistar rats

Abstract

Colorectal cancer induces systemic metabolic dysfunction, including hepato-renal complications that limit treatment and worsen prognosis. This study investigated the effects of dietary crab-derived chitosan on hepato-renal dysfunction accompanying 1,2-dimethylhydrazine (DMH)–induced colon cancer in rats. Male Wistar rats received DMH injections (65 mg/kg weekly for 10 weeks), followed by an 8-week dietary intervention with chitosan (2.5%, 5.0%, 7.5% w/w), capecitabine, or control diets. Liver, kidney, and blood samples were processed for biochemical analyses. DMH induction elevated serum carcinoembryonic antigen 9.4-fold, confirming carcinogenesis. Cancer animals exhibited profound dyslipidemia (49-81% increases in serum, hepatic, and renal triglycerides and cholesterol), severe oxidative stress (60-80% antioxidant enzyme depletion, 4.5-fold hepatic malondialdehyde elevation), hepatic inflammation (2.4-fold NF-κB, 63% COX-2, 58% TNF-α increases), and renal tumor suppressor dysregulation (74% APC, 89% β-catenin suppression). Chitosan dose-dependently ameliorated all parameters, with 7.5% chitosan achieving efficacy comparable to capecitabine while preserving hematological function. Mechanistically, chitosan suppressed HMG-CoA reductase (44% reduction), restored antioxidant defenses, and inhibited NF-κB inflammatory signaling. Histopathology confirmed reduced hepatic steatosis and renal hyperchromicity. Notably, chitosan alone did not disrupt basal metabolic or redox homeostasis. These findings establish chitosan as a promising adjunctive agent for hepato-renal protection in colorectal cancer, warranting clinical translation studies.