Synergistic Effects of L-Arginine and Metformin on Oxidative Stress, Inflammation and Glucometabolic Enzymes in Diabetic Rats

Background and Objective: Diabetes is a complex metabolic disorder characterized by impaired glucose regulation, leading to glucose intolerance and hyperglycemia. This study explores the effects of L-arginine supplementation on inflammation, glucometabolic enzymes and oxidative stress biomarkers in male Wistar rats with alloxan-induced diabetes. Materials and Methods: The 50 adult male Wistar rats were divided into 5 groups of 10. Group A (control) received normal saline. Group B was induced with diabetes using alloxan. Groups C, D and E received alloxan plus metformin, L-arginine, or both for six weeks. Inflammation, oxidative stress and key glucose-regulating enzymes were assessed post-study. The data were presented as Mean±Standard error. One-way Analysis of Variance (ANOVA) was employed to assess statistical differences between groups, followed by Tukey’s post hoc test for individual comparisons. A 95% confidence interval was applied and results with p<0.05 were deemed statistically significant. Results: The combination of L-arginine and metformin significantly lowered blood glucose levels compared to the diabetic group. The combination therapy also decreased malondialdehyde levels, increased superoxide dismutase and catalase activity and reduced inflammatory markers like TNF-α, IL-6 and C-reactive protein, indicating improved glucose metabolism over individual therapies. Conclusion: In male Wistar rats with alloxan-induced diabetes, the combined administration of L-arginine and metformin significantly reduces inflammation, oxidative stress and dysregulation of glucometabolic enzymes. These findings suggest that combination therapy may be an effective strategy for managing diabetes and its complications.