Ghaemmaleki Faezeh, Mohammadi Perham, Baeeri Maryam, Navaei-Nigjeh Mona, Abdollahi Mohammad, Mostafalou Sara
Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Iran.
Department of Physiology and Pharmacology, School of Medicine, Ardabil University of Medical Sciences, Iran.
Heliyon. 2020 Mar 9;6(3):e03562. doi: 10.1016/j.heliyon.2020.e03562. eCollection 2020 Mar.
Tributyltin (TBT) is known as an endocrine disruptor able to interfere with estrogen receptors (ERs) leading to toxic effects on the related endocrine pathways. TBT is an obesogen, reported to disrupt glucose homeostasis leading to diabetes. The aim of this study was to assess the influence of TBT and β-estradiol on the pancreatic islets of Langerhans in simultaneous exposures.
Pancreatic islets of 15 male rat were isolated and exposed to TBT (10 μM), β-estradiol, and TBT plus β-estradiol for 24 h. Therewith, cellular viability, oxidative stress, apoptosis, and insulin secretion markers were investigated.
TBT decreased the viability and increased the apoptosis, reactive oxygen species, and insulin secretion TBT led to increased amounts of apaptosis, reactive oxygen species (ROS), and insulin secretion in pancreatic islets; however, cellular viability was reduced. Co-exposure with β-estradiol ameliorated the entire mentioned variables near to the control level.
These results showed that β-estradiol protect pancreatic islets of Langerhans against TBT-induced toxicity by counteracting oxidative stress and apoptosis as well as insulin secretion. In this way, it is postulated that pancreatic ER pathways particularly in β-cells might be the determinant target of toxic effects of xenoestrogens like TBT. Hence, evaluation of xenoestrogens-induced ER dysfunction in the endocrine pancreas can be helpful in diabetic risk assessment of these contaminants. Pharmacological modifications of ER pathway in the β-cells seems promising for better management of diabetes.
三丁基锡（TBT）是一种内分泌干扰物，能够干扰雌激素受体（ERs），对相关内分泌途径产生毒性作用。TBT是一种致肥胖物，据报道会破坏葡萄糖稳态，导致糖尿病。本研究的目的是评估TBT和β-雌二醇同时暴露对胰岛的影响。
分离15只雄性大鼠的胰岛，将其暴露于TBT（10μM）、β-雌二醇以及TBT与β-雌二醇的混合物中24小时。据此，研究细胞活力、氧化应激、细胞凋亡和胰岛素分泌标志物。
TBT降低了细胞活力，增加了细胞凋亡、活性氧和胰岛素分泌。TBT导致胰岛中细胞凋亡、活性氧（ROS）和胰岛素分泌增加；然而，细胞活力降低。与β-雌二醇共同暴露使上述所有变量改善至接近对照水平。
这些结果表明，β-雌二醇通过对抗氧化应激、细胞凋亡以及胰岛素分泌，保护胰岛免受TBT诱导的毒性。据此推测，胰腺ER途径，尤其是β细胞中的ER途径，可能是TBT等外源性雌激素毒性作用的决定性靶点。因此，评估外源性雌激素诱导的内分泌胰腺ER功能障碍，有助于对这些污染物进行糖尿病风险评估。对β细胞中ER途径进行药理学修饰，似乎有望更好地管理糖尿病。
