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

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

Core Tip: L-arginine (L-Arg) exhibits dose-dependent effects in diabetic cardiomyopathy, with low doses improving lipid profiles and high doses exacerbating oxidative stress and inflammation. This letter emphasizes the need for targeted interventions, such as nuclear factor erythroid 2-related factor 2 activation, nitric oxide synthase modulation, and combination therapies, to mitigate these adverse effects and enhance L-Arg’s clinical safety, offering safer therapeutic options for diabetic patients at risk of cardiovascular complications.