Abstract
            Introduction: An oxidative stress and angiotensin II (Ang II) contribute significantly in the  pathogenesis of diabetic nephropathy (DN). Therefore, interventions targeting these factors are  anticipated to significantly contribute to inhibiting the progression of diabetic kidney disease.  
  Objectives: The aim of this study was to assess the impact of a combination of rosmarinic acid  (RA) and angiotensin receptor blockers (ARBs) in preventing mesangial expansion and reducing  glomerular volume in streptozotocin (STZ)-induced diabetic rats.  
  Materials and Methods: We observed experimental animals, 16 adults male Wistar rats, which were  randomly grouped into 4 groups (n=4 per group): negative and positive control groups and diabetic  rats treated with RA 75 mg/kg and candesartan 1 mg/kg (treatment group 1) and RA therapy 75  mg/kg and losartan 2.5 mg/kg (treatment group 2). Following 8 weeks of therapy, the renal histology  was assessed to evaluate mesangial expansion and glomerular volume.  
  Results: In comparison to the positive control, treatment group 1 demonstrated a significant  inhibition of mesangial expansion (MD: -19.92; 95% CI: -21.97, -17.87; P<0.001) and decreased  glomerular volume (MD: 2669.06; 95% CI: 2066.31, 3271.80; P<0.001). Similarly, treatment  group 2 significantly inhibited mesangial expansion (MD: -19.21; 95% CI: -21.26, -17.16; P<0.001)  and decreased glomerular volume (MD: 2488.04; 95% CI: 1885.29, 3090.78; P<0.001) compared  to the positive control. While treatment group 1 exhibited better effects than treatment group 2,  although the difference was not statistically significant.  
  Conclusion: In STZ-induced diabetic rats, combination therapy of RA with candesartan or losartan  can inhibit mesangial expansion and decrease glomerular volume.