Ramipril and resveratrol co-treatment attenuates RhoA/ROCK pathway-regulated early-stage diabetic nephropathy-associated glomerulosclerosis in streptozotocin-induced diabetic rats

Environ Toxicol. 2019 Jul;34(7):861-868. doi: 10.1002/tox.22758. Epub 2019 May 7.

Abstract

Clinical studies have shown that hyperglycemia can induce early-stage diabetic nephropathy (DN). Furthermore, oxidative stress, tubular epithelial-mesenchymal transition and extracellular matrix accumulation promote the progression of DN to chronic kidney disease and tubulointerstitial fibrosis. It is necessary to initiate treatment at the early stages of DN or even during the early stages of diabetes. In this work, rats with streptozotocin (STZ)-induced diabetes mellitus (DM) presented early DN symptoms within 45 days, and collagen accumulation in the glomerulus of the rats was primarily mediated through the RhoA/ROCK pathway instead of the TGF-β signaling pathway. Resveratrol (15 mg/kg/day) and ramipril (10 mg/kg/day) co-treatment of STZ-induced DN rats showed that glomerulosclerosis in early-stage DN was reversible (P < .05 compared with that in STZ-induced DM rats). The results of this study support early intervention in diabetes or DN as a more efficient therapeutic strategy.

Keywords: diabetes mellitus; diabetic nephropathy; glomerulosclerosis; ramipril; resveratrol.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / prevention & control*
  • Disease Progression
  • Drug Therapy, Combination
  • Glomerulosclerosis, Focal Segmental / pathology
  • Glomerulosclerosis, Focal Segmental / prevention & control*
  • Kidney / drug effects*
  • Kidney / pathology
  • Male
  • Ramipril / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol / administration & dosage*
  • Severity of Illness Index
  • Signal Transduction / drug effects
  • Streptozocin
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Streptozocin
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein
  • Ramipril
  • Resveratrol