Cannabinoid receptor agonist WIN 55,212-2 modulates systemic inflammatory and oxidative stress responses in...

Hyperglycemia, a clinical hallmark of diabetes mellitus (DM)-a chronic metabolic disorder-induces oxidative stress and persistent low-grade inflammation, subsequently enhancing the release of pro-inflammatory cytokines through NF-κB activation. Recent studies have highlighted the significant role of the endocannabinoid system in the pathogenesis of metabolic diseases; however, evidence regarding the ability of WIN 55,212-2 to modulate diabetes-associated oxidative stress and inflammation remains limited. Therefore, this study aimed to evaluate the effects of the CB1/CB2 receptor agonist WIN 55,212-2 on systemic inflammatory and oxidative stress responses in an insulin-deficient STZ-induced diabetic rat model, with metformin included as a pharmacological reference. In this context, STZ-induced diabetic rats were administered intraperitoneally with increasing logarithmic doses of WIN 55,212-2. At the end of the study, glycemic parameters, inflammatory markers, and oxidative stress parameters were evaluated in comparison with the metformin-treated group. Notably, the 1 mg/kg dose of WIN 55,212-2 reduced blood glucose levels, attenuated inflammatory responses, and improved oxidative stress parameters, with effects that partially overlapped with those observed in the metformin reference group across several key endpoints. These findings suggest that WIN 55,212-2, particularly at 1 mg/kg, modulates diabetes-associated inflammatory and oxidative stress pathways in this insulin-deficient preclinical model, with partially overlapping effects compared with metformin.