Comparative effects of valsartan and irbesartan combined with rosmarinic acid on serum malondialdehyde and albuminuria in diabetic nephropathy rat models

Abstract

Diabetic nephropathy is a major microvascular complication of diabetes mellitus and remains a leading cause of chronic kidney disease. Oxidative stress is a central mechanism in its pathogenesis, and malondialdehyde (MDA) is widely used as a biomarker of lipid peroxidation. The aim of this study was to compare the effects of rosmarinic acid combined with valsartan or irbesartan on serum MDA and urinary albumin levels in a rat model of diabetic nephropathy. A laboratory-based experimental study with a randomized post-test-only controlled group design was conducted from April 2021 to April 2022. Male Wistar rats were rendered diabetic by a high-fat diet followed by streptozotocin administration and were allocated to a non-diabetic group, an untreated diabetic group, and two treatment groups receiving rosmarinic acid in combination with either valsartan or irbesartan. Serum MDA and urinary albumin levels were measured, and between-group comparisons were performed using one-way analysis of variance followed by post hoc Tukey analysis when appropriate, with statistical significance set at p<0.05. No significant difference in serum MDA levels was observed among groups (p=0.512). In contrast, urinary albumin levels differed significantly among groups (p=0.041). Post hoc Tukey analysis showed that urinary albumin levels differed significantly between the untreated diabetic group and rosmarinic acid–valsartan groups (mean difference (MD): 2.59; 95%CI: 0.46 to 4.73; p=0.013) and between the untreated diabetic and rosmarinic acid–irbesartan groups (MD: 2.59 μg/mL; 95%CI: 0.45 to 4.72; p=0.014). The combination of rosmarinic acid with either valsartan or irbesartan was not associated with a significant difference in serum MDA levels in this model, although lower urinary albumin levels were observed in the treatment groups. This finding suggests that serum MDA alone may not fully reflect the potential nephroprotective effects of these combinations, which should be further evaluated using a broader panel of oxidative stress biomarkers.