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Naringenin ameliorates streptozotocin-induced diabetic rat renal impairment by downregulation of TGF-β1 and IL-1 via modulation of oxidative stress correlates with decreased apoptotic events

Pharm Biol. 2016 Sep;54(9):1616-27. doi: 10.3109/13880209.2015.1110599. Epub 2016 Feb 29.

Abstract

Context: Naringenin, a flavonone and a nutritive antioxidant which is mostly obtained from grapefruit, orange or tomato skin, has been extensively studied due to its radical scavenging activity.

Objective: The present study investigates the protective effect of naringenin on rat kidney after streptozotocin-induced diabetes.

Materials and methods: Sixty male Wistar rats were divided into six groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg/kg) in groups II, III and IV. Naringenin 5 mg/kg body weight was given to groups III and V, but 10 mg/kg was given to groups IV and VI, orally once a day for 10 weeks. After which all animals were sacrificed, and the biochemical, histopathological, immunohistochemical and apoptotic assays were conducted.

Results: Naringenin treatment with 5 and 10 mg/kg significantly decreased (p < 0.05) the serum biochemical parameters, elevated tissue malondialdehyde levels and increased (p < 0.01) the reduced superoxide dismutase, catalase and reduced glutathione enzyme activities in the diabetic kidney. Diabetes-induced naringenin-treated groups showed an improved histology and revealed a significant reduction in apoptosis activity (7.2 ± 0.01 and 1.8 ± 0.05) and in expression of TGF-β1 (18.9 ± 3.4 and 10.2 ± 2.1) at a dose of 5 and 10 mg/kg, respectively. Similarly, in contrast to the diabetic group, a significant difference was observed in the IL-1 expression (15.68 ± 4.3) in 5 mg/kg and (9.85 ± 2.1) in 10 mg/kg naringenin-treated groups.

Conclusion: Naringenin acts as a protective agent in diabetic renal impairment by altering oxidative stress, modulation of cytokines expression and apoptotic events.

Keywords: Catalase; diabetes; histopathology; immunohistochemistry; malondialdehyde; reduce glutathione; terminal dUTP nick end-labeling.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / chemically induced
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / prevention & control*
  • Dose-Response Relationship, Drug
  • Flavanones / pharmacology*
  • Hypoglycemic Agents / pharmacology*
  • Interleukin-1 / metabolism*
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Oxidative Stress / drug effects*
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Streptozocin
  • Time Factors
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Antioxidants
  • Biomarkers
  • Blood Glucose
  • Flavanones
  • Hypoglycemic Agents
  • Interleukin-1
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Streptozocin
  • naringenin