Protective effects of captopril in diabetic rats exposed to ischemia/reperfusion renal injury

J Pharm Pharmacol. 2013 Feb;65(2):243-52. doi: 10.1111/j.2042-7158.2012.01585.x. Epub 2012 Sep 7.

Abstract

Objectives: To investigate the potential protective effects of captopril, the angiotensin-converting enzyme inhibitor, in diabetic rats exposed to ischaemia/reperfusion (I/R) renal injury.

Methods: Following successful induction of diabetes, captopril treatment (50 mg/kg/day, p.o.) was applied for 4 weeks, after which bilateral renal ischaemia was induced for 30 min followed by reperfusion for 24 h.

Results: Captopril significantly attenuated hyperglycaemia and hypoinsulinaemia in diabetic rats, and significantly reduced the elevations of serum creatinine and aldosterone levels, and renal malondialdehyde, tumour necrosis factor-α and nitric oxide (NO), and prevented the depletion of reduced glutathione caused by I/R in diabetic rats. Histopathological renal tissue damage induced by I/R in diabetic rats was ameliorated by captopril treatment. Immunohistochemical analysis revealed that captopril significantly attenuated the reduction of insulin content in pancreatic islet β-cells, and decreased the I/R-induced expression of inducible NO synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin and heme oxygenase-1 in the kidney tissue of diabetic rats.

Conclusions: Captopril represents a potential candidate to reduce the risk of renal injury induced by ischaemia/reperfusion in type 2 diabetes.

MeSH terms

  • Aldosterone / blood
  • Aldosterone / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Captopril / pharmacology*
  • Caspase 3 / metabolism
  • Creatinine / blood
  • Creatinine / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Fas Ligand Protein / metabolism
  • Glutathione / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism
  • Hyperglycemia / blood
  • Hyperglycemia / metabolism
  • Hyperglycemia / pathology
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Kidney / blood supply*
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control
  • Male
  • Malondialdehyde / metabolism
  • Microtubule-Associated Proteins / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / blood
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Survivin
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Birc5 protein, rat
  • Fas Ligand Protein
  • Insulin
  • Microtubule-Associated Proteins
  • NF-kappa B
  • Survivin
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Aldosterone
  • Malondialdehyde
  • Captopril
  • Creatinine
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Caspase 3
  • Glutathione