Involvement of mitochondrial dysfunction and oxidative stress in the nephrotoxicity induced by high-fat diet in Sprague-Dawley rats.

Abstract

The prevalence of obesity-associated kidney injury has increased, yet the precise extent of the injury and its underlying mechanisms remain unclear. This study used a Sprague-Dawley (SD) rat model to simulate human exposure scenarios, with the objective of investigating the involvement of mitochondria in obesity-induced renal toxicity. Biochemical analysis revealed significant increases in serum creatinine, cystatin C, urinary protein, urinary microalbumin, and urinary α1-microglobulin levels in rats fed a high-fat diet, indicating a notable decline in glomerular filtration function. Histopathological examination showed mild to moderate degeneration in renal tubular epithelial cells, slight glomerular enlargement, fusion and disappearance of pedunculated cell, and decreased electron density of mitochondrial matrix and cristae, indicating the impaired filtration function of kidney. Furthermore, the study found reduced mitochondrial membrane potential and superoxide dismutase (SOD) levels, along with increased malondialdehyde (MDA) levels, signifying elevated mitochondrial oxidative stress in the kidneys of high-fat diet-fed rats. Additionally, a decrease in the number of mitochondrial proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and uncoupling protein-2 (UCP-2)-positive cells, as well as reduced protein expression levels in the mitochondria, suggests a reduced renal mitochondrial resistance to oxidative stress. Collectively, these findings indicate that a high-fat diet triggers abnormalities in both renal filtration and structural functionality in SD rats. The observed reduction in renal mitochondrial density and the elevation in oxidative stress levels could potentially serve as underlying mechanisms.