The Protective Effect of Pomegranate (Punica granatum) against Oxidative Stress and Nephropathy Induced by Diabetes in Male Rats: A Biochemical, Molecular and Histopathological Study

Aims: Diabetes mellitus is a significant health problem worldwide and type II diabetes is one of the main health problems facing Saudi society, which is often caused by obesity and increased cholesterol in the blood. Due to the seriousness of diabetes and its complications, the present study was designed to examine the renoprotective effect of pomegranate in diabetes induced oxidative stress and kidney injury.

Study Design: Adult male Albino rats (200–250 g) were used in this study. Diabetes was induced by streptozotocin (45 mg/kg) followed by treatment for 8 weeks. The animals were randomly divided into four groups (each group, n = 10): normal control (NC); non-diabetic animals fed on commercial diet, diabetic group (DG); diabetic animals fed on commercial diet, pomegranate treated group (PTG); diabetic animals fed on experimental diet contains 20% dried pomegranate, and drug treated group (MTG); diabetic animals fed on commercial diet and treated with metformin (500 mg/kg).

Methodology: At the end of the experimental study (8 weeks) blood glucose levels, lipid peroxidation, biochemical analysis of oxidative stress parameters and biomarkers of kidney damage were determined. The mRNA expression level of oxidative stress defense genes (SOD, CAT ,GR and GPx), as well as the NADPH oxidase (subunits p22phox and p47phox) and the inflammatory factors regulator gene, NF-κB were also evaluated in kidney homogenates using semi-quantitative RT-PCR analysis. Furthermore, histopathological evaluation of kidney was also studied.

Results: Treatment with pomegranate significantly ameliorated the elevated oxidative stress levels in STZ induced diabetic rats resulting in decreased lipid peroxidation and NO concentration, and increased endogenous antioxidant enzymes levels (SOD and GSH). Biomarkers of kidney damage (urea and creatinine) and blood glucose levels were significantly normalized in pomegranate treated group compared to the diabetic group. At the molecular level, a significant enhancement of gene expression of the antioxidant enzyme (SOD, CAT, GR and GPx) was observed in pomegranate treated group compared to the diabetic group. In contrast, significant down-regulation of the NADPH oxidase subunits (p22phox and p47phox) as well as the inflammatory factors regulator gene, NF-κB was recorded. Moreover, the histopathological examinations confirmed the protective effects of pomegranate by normalizing the kidney damage.

Conclusion: This study validates pomegranate as a promising candidate in preventing diabetes associated complications such as nephropathy through its antioxidant activity and its effects on the activity and regulation of oxidative stress defense gene expression.