Resveratrol ameliorates long-term structural, functional and metabolic perturbations in a rat model of donor nephrectomy: Implication of SIRT1

[Display omitted] •UNX rats showed pathological changes in the remaining kidney and metabolic changes.•The remaining kidney showed decreased SIRT1 expression and elevated MDA levels.•Early resveratrol administration induced SIRT1 expression and decreased renal MDA.•Resveratrol protected the remaining kidney against damage, and dysmetabolism. Nephron loss by uninephrectomy (UNX) as in renal donors is followed by structural and functional changes in the remaining kidney, and systemic metabolic changes. SIRT1, a NAD-dependent deacetylase, deficiency is implicated in renal fibrosis and dysfunction. We investigated the effects of resveratrol, a plant-derived polyphenol antioxidant and SIRT1 inducer on renal SIRT1 expression and metabolic consequences post-nephrectomy. Adult male UNX rats were administered resveratrol 20 mg/kg/day starting 1-week post-nephrectomy till termination 3, 5 or 7 months later. UNX triggered renal hypertrophy and progressive glomerular fibrosis, with increased serum urea, creatinine and Na+, and proteinuria. The glucose tolerance and lipid profile deteriorated. Resveratrol upregulated renal SIRT1 expression, limited the renal hypertrophy and fibrotic changes, and markedly attenuated renal function and lipid peroxidation. With prolonged resveratrol administration, glucose tolerance and lipid profile were restored to control values. In conclusion, resveratrol may be potentially beneficial as adjuvant therapy in human kidney donors.