Estrogens counteract tributyltin-induced toxicity in the rat islets of Langerhans.

BACKGROUND: 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 ß-estradiol on the pancreatic islets of Langerhans in simultaneous exposures. EXPERIMENTAL: Pancreatic islets of 15 male rat were isolated and exposed to TBT (10 µM), ß-estradiol, and TBT plus ß-estradiol for 24 h. Therewith, cellular viability, oxidative stress, apoptosis, and insulin secretion markers were investigated. RESULTS: 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 ß-estradiol ameliorated the entire mentioned variables near to the control level. CONCLUSION: These results showed that ß-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 ß-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 ß-cells seems promising for better management of diabetes.

Mechanistic assessment of cadmium toxicity in association with the functions of estrogen receptors in the Langerhans islets.

OBJECTIVES: Diabetes is a metabolic disease with an increasing prevalence for which finding new and efficient therapeutic approaches has always been a challenge. Preserving integrity and functionality of pancreatic ß-cells as the only source of insulin in the body is such a case. To achieve this goal different cellular targets have been proposed among which pancreatic estrogen receptors have gotten much attention. In this work, we evaluated the integrity and function of islets of Langerhans under the influence of factors known to intervene with estrogen receptors. Cadmium, a toxic heavy metal, has been recently shown to interact with estrogen receptors but its toxicity in the pancreatic islets regarding this mechanism remains unclear. MATERIALS AND METHODS: Isolated islets of Langerhans from the pancreas of rats were grouped and treated with cadmium chloride and also cadmium chloride plus ß-estradiol. After 24 hr incubation, parameters of cellular viability, oxidative stress, apoptosis, and insulin secretion were measured . RESULTS: The results indicated that cadmium reduced viability of the islets along with an increase in the formation of reactive oxygen species and apoptosis markers, and ß-estradiol, in turn, was able to alleviate these disturbances to some extent, implicating the protective role of ß-estradiol against pancreatic toxicity of cadmium. CONCLUSION: It can be concluded that modification of estrogen receptors in the endocrine pancreas and especially ß-cells may be a promising target to find a new therapeutic strategy for diabetes and even uncovering mechanisms of environmental toxicants that have been known as risk factors of diabetes.