Vitamin C Ameliorates Potassium Dichromate‐Induced Oxidative Stress and Mitochondrial Dysfunction via PGC‐1α/Nrf‐2/TFAM Pathway

Exposure to potassium dichromate (K₂Cr₂O₇) is well known for its nephrotoxic effects on humans and animals. This study investigated the protective effects of vitamin C against K₂Cr₂O₇-induced nephrotoxicity, focusing on its impact on altered carbohydrate metabolism, mitochondrial dysfunction, and associated molecular mechanisms in the cortical and medullary kidney segments. Male Wistar rats (n = 8) were divided into four groups: Group I received saline, Group II received a single 250 mg/kg body weight (bwt) intraperitoneal (i.p.) injection of vitamin C, Group III received K₂Cr₂O₇ (15 mg/kg bwt, i.p.), and Group IV received vitamin C 6 h before K₂Cr₂O₇ administration. Vitamin C significantly mitigated K₂Cr₂O₇-induced nephrotoxic effects, restoring normal renal function and histological architecture. It preserved the activities of glycolytic and gluconeogenic enzymes altered by K₂Cr₂O₇. Additionally, vitamin C mitigated K₂Cr₂O₇-induced mitochondrial dysfunction by maintaining tricarboxylic acid (TCA) cycle enzymes, electron transport chain proteins, mitochondrial DNA copy number, and ATP content. It also reduced oxidative stress markers and enhanced antioxidant enzyme activity. The protective mechanism of vitamin C against K₂Cr₂O₇-induced renal damage involved upregulation of the protein expression of peroxisome proliferation-activated receptor-γ coactivator-1α (PGC-1α), which further elevated the protein expression of nuclear factor erythroid 2-related factor-2 (Nrf-2) and transcription factor A, mitochondrial (TFAM), crucial for protecting cells from oxidative stress, enhancing mitochondrial function, and promoting cellular health. Overall, this study highlights the significant protective role of vitamin C against K₂Cr₂O₇-induced renal damage by preserving carbohydrate metabolism and mitigating mitochondrial dysfunction through the PGC-1α/Nrf-2/TFAM pathway, offering valuable insights into its protective mechanisms in nephrotoxicity.