Double-edged sword of L-arginine in diabetes: Exploring anti-inflammatory and antioxidant strategies

World J Diabetes. 2025 Apr 15;16(4):104007. doi: 10.4239/wjd.v16.i4.104007.

Abstract

The article by Mansouri et al provides a comprehensive investigation into the effects of L-arginine (L-Arg) on diabetic cardiomyopathy. The authors conclude that while a low dose (0.5 g/kg) of L-Arg improves lipid profiles and reduces body weight, higher doses (≥ 1 g/kg) exacerbate oxidative stress, inflammation, and myocardial damage. In this letter, we aim to expand on the potential role of anti-inflammatory and antioxidant strategies in mitigating these adverse effects. Specifically, we focus on nuclear factor erythroid 2-related factor 2 activation and nitric oxide synthase modulation. These strategies could enhance the clinical utility of L-Arg by preserving its metabolic benefits while reducing its cardiotoxic risks. We believe this perspective will stimulate future research on L-Arg-based therapies in patients with diabetes, with an emphasis on optimizing dosage and exploring synergistic co-therapies.

Keywords: Diabetic cardiomyopathy; L-arginine; Nitric oxide synthase; Nuclear factor erythroid 2-related factor 2; Oxidative stress.