Combination of Naringenin and Lisinopril Ameliorates Nephropathy in Type-1 Diabetic Rats

Endocr Metab Immune Disord Drug Targets. 2021;21(1):173-182. doi: 10.2174/1871530320666200516163919.

Abstract

Background: Diabetes is a metabolic disorder affecting a large percentage of the population worldwide. The chronic hyperglycemic condition leads to the generation of advanced glycation end products, reactive oxygen species and inflammatory cytokines, which worsen the functioning of the kidney. Clinical management of diabetic nephropathy is difficult as it requires a multi-focused approach. Hence, a combination of lisinopril a drug used in clinical practice for nephropathy, and naringenin, a flavonoid reported to have a significant effect in nephropathy, may show additive or synergistic effect with less side effects.

Objective: The objective of the present study was to evaluate the effect of a combination of lisinopril with naringenin in diabetic nephropathy.

Methods: Diabetes was induced in male Sprague Dawley rats by streptozotocin (55 mg/kg, i.p.). After four weeks of diabetes induction animals were treated with naringenin alone and a combination of Lisinopril and naringenin for the next four weeks. At the end of the study, various urine and biochemical parameters were evaluated. Oxidative stress parameters like malondialdehyde, reduced glutathione; catalase and superoxide dismutase for kidney tissues were estimated and histopathology studies of kidneys were carried out.

Results: The combination of lisinopril (10 mg/kg) and naringenin (25 and 50 mg/kg) treatment showed significant improvement in the biochemical and urine parameters. Combination treatment also attenuated renal oxidative stress and renal damage as observed in histopathological studies.

Conclusion: Treatment with a combination of lisinopril and naringenin showed a promising effect on diabetic nephropathy in rats.

Keywords: Diabetic nephropathy; Type-1 diabetes; diabetic complications; flavonoids; lisinopril; naringenin.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / prevention & control*
  • Drug Therapy, Combination
  • Flavanones / administration & dosage*
  • Flavanones / pharmacology
  • Kidney / drug effects
  • Kidney / pathology
  • Lisinopril / administration & dosage*
  • Lisinopril / pharmacology
  • Male
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Streptozocin

Substances

  • Blood Glucose
  • Flavanones
  • Reactive Oxygen Species
  • Streptozocin
  • Lisinopril
  • naringenin