LIPID PROFILE OF BLOOD SERUM IN MICE UNDER CONDITIONS OF BISPHENOL A ADMINISTRATION AND VITAMIN A DIFFERENT SUPLEMENTATION
DOI:
https://doi.org/10.31861/biosystems2019.02.115Ключові слова:
bisphenol A, hypercholesterolemia, dislipidemia, retinoids, vitamin AАнотація
Bisphenol A (BPA) is an endocrine disruptor and one of the highest volume chemicals produced worldwide and extremely prevalent in our environment. Many epidemiological studies show that BPA exposure could cause various adverse health problems related to metabolic disorders in humans, including obesity, insulin resistance, type 2 diabetes, hepatic injury, dyslipidemia and cardiovascular diseases. Retinoids are involved in a wide range of biological processes through binding and activation of nuclear receptors: RAR and RXR. RAR/RXR-mediated signaling has been implicated in the regulation of glucose and lipid metabolism. In accordance with mentioned above, the purpose of the study was to determine the lipid profile of blood serum and glucose tolerance in mice under conditions of bisphenol A administration and different vitamin A consumption. The experimental animals were wild type mice (WT) with normal retinoids supplementation and transgenic mice (Lrat-/-) that are unable to esterify of retinol and do not have retinoid stores in liver. Bisphenol A (BPA), dissolved in corn oil (used as a vehicle), was administered per os daily for 3 days at a dose of 50 mg/kg body weight. Vitamin A overconsumption was modeled by administration of retinyl acetate (Rac) in a very high dose of 3000 IU at 12 h intervals for 3 days. In the present study dyslipidemia was observed in the mice received 50 mg/kg BPA represented by significant higher triglycerides (at 1,4-fold), total cholesterol (at 2,2-fold), LDL-C, VLDL-C and HDL-C (46%, 39% and 2,8-fold respectively) than those mice of control group received vehicle. Administration of BPA also resulted in disruptions of glucose homeostasis, consisting of hyperglycemia (11±1.11 mmol/l) and glucose intolerance of animals. These BPA’s actions were attributed to its ability of binding to nonclassical membrane estrogen receptor as well as the G-protein coupled-receptor 30 (GPR30) and to act through nongenomic pathways. In knockout mice that did not have retinoid stores in the liver, indicators of both lipid profiles and glucose homeostasis were not significantly different from identical indicators of vehicle-treated mice. At the same time, additional 3000 IU retinyl acetate expose simultaneously with administration of 50 mg/kg BPA enhanced the lipogenic effect of xenobiotics in the wild type animals and induce its obesonic adverse effect in Lrat-/- mice, that possibly accompanied with activation of LXR regulated genes by retinoic acid, which is known to be responsible for lipid metabolism. Thus, BPA exposure results in metabolic disorders consisting of hyperglycemia, glucose intolerance, hypercholesterolemia and hyperlipidemia. Retinoids enhanced the BPA action as an obesogen.
Посилання
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