Nano-Resveratrol Mitigates Dimethylhydrazine-Induced Colorectal Carcinogenesis in Male Rats: Impact on Oxidative Stress, Antioxidant Defense, and Radiationaugmented Pathways

Abstract

Background: Colorectal cancer remains a major cause of cancer-related mortality worldwide. Antilymphangiogenic strategies, coupled with modulation of oxidative stress and apoptotic pathways, offer potential therapeutic avenues. This study evaluated the anticancer activity of nano-resveratrol against dimethylhydrazine (DMH)-induced colon carcinogenesis in male albino rats. Materials and
Methods: Male albino rats were allocated into five groups: Group 1 normal control receiving saline i.p. for 30 weeks; Group 2 DMH only (20 mg/kg b.w. s.c., weekly for 9 weeks); Group 3 DMH followed by resveratrol three times weekly for 21 weeks); Group 5 DMH + NRSV and exposure to low-dose gamma radiation (0.25 Gy) during the post-DMH period. Endpoints included oxidative stress markers [malondialdehyde (MDA)], reduced glutathione (GSH), total antioxidant capacity (TAC), and ROS; apoptosis was assessed by Annexin V flow cytometry. Histopathological examination of the colon was performed after euthanasia, with evaluation for dysplasia, adenomas, adenocarcinoma, and lymphangiogenesis markers where applicable. Results: DMH administration induced clear colonic
carcinogenesis characterized by mucosal dysplasia progressing to adenocarcinoma in a subset of animals. Histopathology revealed architectural distortion, glandular atypia, increased mitotic figures, and focal invasive patterns in affected groups. Compared with normal controls, DMH-treated groups showed elevated MDA and ROS levels, with suppressed GSH and TAC, indicating oxidative stress.
Annexin V analysis demonstrated increased apoptotic populations in response to DMH, reflecting compensatory cytotoxic responses. NRSV, both alone and in combination with radiation, moderated oxidative stress by reducing MDA and ROS and restoring GSH and TAC toward control levels. Conclusion: Nano-resveratrole demonstrated potent anticarcinogenic activity against DMH-induced colorectal carcinogenesis in male albino rats. The beneficial effect were mediated, at least in part, by attenuation of oxidative stress, restoration of antioxidant defenses, and modulation of apoptotic pathways. When combined with radiation, NRSV showed further improvement in histological and molecular endpoints, suggesting a potential combinatorial approach for colorectal cancer prevention or adjunct therapy.