Journal
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
Volume 78, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.etap.2020.103387
Keywords
Oxidative stress; Lipid peroxidation; Pro-inflammatory cytokines; Metabolic disorder; BPA exposure
Funding
- Higher Education Commission of Pakistan [5661/Punjab/NRPU/RD/HEC/2016, 6429/Punjab/NRPU/RD/HEC/2016, 8365/Punjab/NRPU/RD/HEC/2017]
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Bisphenol-A (BPA), a widespread endocrine-disrupting chemical, has been recognized as a risk factor for metabolic disorders. BPA is considered to be involved in the impairment of carbohydrate and lipid metabolism but the underlying mechanisms still need to be elucidated. Present study was aimed to investigate the impact of BPA exposure on enzymatic and metabolic pathways that are responsible to regulate the carbohydrate and lipid metabolism. Experimental rats were exposed to different doses of BPA (50, 500, 2500 and 5000 mu g/kg/day orally) dissolved in 1.5% dimethyl sulfoxide for a period of 3 months. Serum level of key metabolic enzymes (alpha-amylase, a-glucosidase, hexokinase, glucose-6-phosphatase and HMG-CoA-reductase) was measured by ELISA method. BPA-exposure suppressed the mRNA expression of gene encoding insulin resulting in poor insulin production. While hexokinase, acetyl-CoA carboxylase and squalene epoxide were up-regulated upon BPA exposure that justified the increased lipid profile. Moreover, BPA exposure showed considerably decreased glucose uptake through insulin signaling via Akt/GLUT4 pathways. There was a significant (p < 0.001) reduction in tissue level of glucose transporters. BPA significantly (p < 0.001) decreased the serum levels of oxidative stress biomarkers (GSH, CAT, and SOD). Serum levels of leptin, TNF-alpha, and IL-6 were rapidly increased upon exposure to BPA (p < 0.001). It was clearly evident from this study that BPA disturbed the carbohydrate and lipid metabolism after chronic exposure. It also accelerated the inflammatory processes by increasing the oxidative stress which ultimately lead towards the insulin resistance and impaired carbohydrate and lipid metabolism.
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