Introduction: An antidiabetic potential has long been reported for Rhus coriaria L. (sumac) and recent studies have proven a curative leverage against gentamicin (GM)-induced nephrotoxicity.
Aim of the Work: The current study hypothesized a possible Low-density lipoprotein-related receptor protein 2 (LRP2) expression modulatory effect, as an ameliorative mechanism, produced by sumac in GM-induced nephrotoxicity in diabetic rats.
Material and Methods: Forty-two male albino rats were subdivided into control, sumac alone (orally for 14 days), diabetes mellitus (DM, given single intravenous dose of streptozotocin (STZ), GM (intraperitoneal, once daily for 7 days), DM/GM, and DM/GM+sumac groups. Twenty-Four hrs after the last treatment, blood sampling was done for laboratory analysis of blood glucose, urea, and creatinine. The kidneys were harvested and subjected to RT-PCR quantification of LRP2 (megalin) mRNA levels, Hematoxylin and Eosin, Masson trichrome staining, and immunohistochemical assaying for P53, TNF-α, and megalin.
Results: Diabetic rats showed altered biochemical and histological findings which increased in the GM alone group and showed more serious tubular and glomerular injury in GM/DM group including disorganized glomeruli with mesangial degeneration and cellular depletion with hypertrophy of the remaining ones. The renal tubules were enlarged with sloughing and desquamation of the tubular lining cells. This was associated with significant elevation of the renal functions, upregulation of megalin gene/protein expression, in addition to increased P53 and tumor necrosis factor-α (TNF-α). Sumac treatment downregulated megalin gene/protein expression, coupled with regulation of P53 and TNF- α expression and maintenance of the renal functions.
Conclusion: GM injection in already existing STZ-induced diabetic rats led to more serious renal damage, and sumac co-treatment protected against this renal damage, might be via LRP2 blockage dependent P53/TNF-α downregulation.