Background: Diabetes mellitus (DM) is chronic metabolic disease associated with pancreatic β-cell dysfunction, oxidative stress, inflammation, and structural pancreatic injury. The aryl hydrocarbon receptor pathway may contribute to diabetic tissue damage through activation of downstream genes of cytochrome, including CYP1A1 and CYP1B1.
Aim: To investigate the role of AhR signaling in pancreatic injury in alloxan-induced diabetic rats and to evaluate the potential modulatory and protective effects of resveratrol.
Methods: Thirty rats were divided into five groups; sham, diabetic control, diabetic vehicle control, resveratrol-treated diabetic, and AhR blocker-treated diabetic groups. Diabetes was induced by alloxan. Pancreatic expression of CYP1A1, CYP1B1, PPARG, and SLC2A4 was assessed by RT-qPCR. Pancreatic C-peptide, TNF-α, and MDA levels were measured by ELISA. Histopathological changes were evaluated using H&E staining, and correlation analysis was performed using individual animal data.
Results: They show the diabetes increased CYP1A1 and CYP1B1 expression, reduced PPARG and SLC2A4 expression, decreased C-peptide, and elevated TNF-α and MDA. Resveratrol and AhR blockade attenuated these alterations and improved pancreatic architecture. AhR activity correlated negatively with metabolic recovery and C-peptide, and positively with TNF-α and MDA.
Conclusion: AhR signaling is associated with diabetic pancreatic injury, while resveratrol and AhR blockade provide protective effects against oxidative, inflammatory, and structural damage.
Keywords: Resveratrol; diabetes mellitus; aryl hydrocarbon receptor; CYP1A1; CYP1B1; PPARG; SLC2A4; C-peptide; TNF-alpha; MDA; pancreas.