1. Biochemical Impact of Nickel‐Induced Metabolic Impairment and the Protective Effects of Resveratrol and Ascorbic Acid.
- Author
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Feezan, Ali, Afzal, Samina, Shoaib, Syed Muhammad, Rehman, Kanwal, Hussain, Amjad, Akash, Muhammad Sajid Hamid, Shahid, Mudassar, Sadaf, Bushra, and Santos, Mario Ferreira Conceição
- Subjects
INSULIN regulation ,AMINO acid metabolism ,CARBOHYDRATE metabolism ,KIDNEY physiology ,METABOLIC disorders ,HOMEOSTASIS ,ENDOPLASMIC reticulum - Abstract
Nickel exposure is known to induce oxidative stress and inflammation and disrupt critical metabolic pathways, leading to hepatic dysfunction and impaired glucose regulation. This study aimed to evaluate the biochemical effects of nickel‐induced metabolic impairments in an animal model, using a variety of techniques, including ELISA and instrumental analysis, with a specific focus on the expression of key genes involved in insulin regulation and glucose homeostasis. The experiment included four groups: Control, Nickel‐exposed, Nickel‐exposed with standard treatment (ascorbic acid, AA), and Nickel‐exposed with resveratrol (RSV). Serum nickel levels, measured via ICP‐MS, showed a significant increase in the exposed group, with a mean value of 125.74 ± 6.20 ppb. The analysis of various metabolic biomarkers demonstrated that nickel exposure resulted in hyperglycemia, elevated HOMA‐IR, HbA1c, and DPP‐4, increased level of inflammatory cytokines, altered lipid profiles, and impaired liver and kidney function. Nickel exposure triggered inflammation, disrupted carbohydrate metabolism, induced oxidative stress, and altered the expression of genes related to hepatic inflammation, endoplasmic reticulum (ER) stress, and glucose and lipid metabolism. These changes culminated in mitochondrial dysfunction, impaired glucose metabolism, and insulin resistance, as evidenced by reduced expression of GLUT‐2 and GCK—genes critical for glucose uptake and insulin secretion. Elevated serum levels of amino acids, such as glutamate and valine, further indicated disruptions in amino acid metabolism and oxidative stress. Therapeutic interventions with AA and RSV demonstrated significant protective effects: Both compounds mitigated oxidative stress, reduced inflammatory cytokines, and restored normal expression levels of GCK and GLUT‐2, improving glucose metabolism and insulin sensitivity. Additionally, AA and RSV alleviated mitochondrial dysfunction, suppressing the overexpression of UCP2, a protein linked to impaired energy metabolism. Serum amino acid levels were also normalized, highlighting their role in reestablishing metabolic balance. In conclusion, this study highlights the therapeutic potential of AA and RSV in mitigating nickel‐induced hepatic and metabolic disturbances. These findings emphasize the importance of addressing oxidative stress and inflammation in metabolic disorders and position RSV as promising candidate for restoring metabolic homeostasis. Further research is warranted to elucidate the precise molecular mechanisms underlying their protective effects. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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