The effectiveness of antioxidant agents in delaying progression of diabetic nephropathy: A systematic review of randomized controlled trials
Authors: Rahayu Ika , Arfian Nur , Kustanti Christina Yeni , Wahyuningsih Mae Sri Hartati 
Published: June 2024

Introduction: Oxidative stress plays a central role in the pathophysiology of diabetes mellitus and its complications, including diabetic nephropathy. Excessive production of reactive oxygen species (ROS) alters renal metabolic pathways, leading to inflammation, endothelial dysfunction, and fibrosis, ultimately resulting in end-stage renal disease (ESRD). Studies have shown that exogenous antioxidants can improve the pathophysiological condition of patients with diabetic nephropathy. Objective: This systematic review aims to investigate the types of antioxidant agents that inhibit the development of diabetic nephropathy and the effectiveness of antioxidant agent interventions to repair kidney structure and function. Methods: A systematic review of randomized controlled trials that examined the role of antioxidants in improving diabetic nephropathy was conducted. The literature search was performed on PubMed, ScienceDirect, and EBSCO. The inclusion criteria covered articles on the antioxidant activity of herbal extracts and compounds that inhibit the progression of diabetic nephropathy in humans. In addition, the articles were written in English and published between 2012 and 2022. The reporting of the systematic review followed the Preferred Reporting Elements for Systematic Review and Meta-Analysis (PRISMA) guideline. The full texts of all potentially relevant systematic reviews were assessed for quality using the Risk of Bias 2 (RoB 2) tool. Results: A total of 2,367 articles were identified in the three databases, of which only 15 articles met the inclusion criteria. Antioxidant agents that inhibit diabetic nephropathy can be classified as single antioxidants (silymarin, baicalin, epigallocatechin gallate, vitamin E, selenium, curcumin, α-lipoic acid, and tocotrienol-rich vitamin E) and combined antioxidants (α-lipoic acid with vitamin B6, and resveratrol with losartan). Antioxidant agents have been shown to reduce oxidative stress and inflammation, but their role in the progression of fibrosis remains unclear. The oxidative stress marker MDA was significantly reduced by silymarin, curcumin, vitamin E, tocotrienol-rich vitamin E, selenium, ALA, vitamin B, resveratrol and losartan. Silymarin was found to be the most effective (-3.43 µmol/L; 6.02 to 0.83). Compared to silymarin and epigallocatechin gallate, vitamin E was more effective (at -35.4 ng/L; P < 0.001) in reducing inflammation by decreasing TNF-α levels. In addition, tocotrienol-rich vitamin E, silymarin, baicalin, and selenium showed a decrease TGF-β levels, but did not show statistically significant differences between the placebo and intervention groups. Conclusion: Potential antioxidant agents, such as flavonoids, vitamins, fatty acids, and antioxidant minerals, were examined in this systematic review. These agents contribute to reducing markers of oxidative stress and hyperglycemia-induced inflammation. Although several antioxidants play a role in reducing fibrosis markers, the effect does not appear to be statistically significant.