Chronic Exposure to Tributyltin Chloride Induces Pancreatic Islet Cell Apoptosis and Disrupts Glucose Homeostasis in Male Mice

National Key Technology R&D Program of China [2007BAC27B02]; Project 111 of the Ministry of Education [B06016]It has been reported that organotin compounds such as triphenyltin or tributyltin (TBT) induce diabetes and insulin resistance. However, histopathological effects of organotin compounds on the Islets of Langerhans and exocrine pancreas are still unclear. In the present study, male KM mice were orally administered with TBT (0.5, 5, and 50 mu g/kg) once every 3 days. The fasting plasma glucose levels significantly elevated, and the levels of serum insulin or glucagon decreased in the animals treated with TBT for 60 days. In animals treated for 45 days, the number of apoptotic cells in the islets and exocrine pancreas was elevated in a dose-dependent manner. The percentage of proliferating (PCNA-positive) cells was decreased in the islets, while it was increased in exocrine acinar cells. Immunohistochemistry analysis showed that estrogen receptor (ER) and androgen receptor (AR) were present in vascular endothelium, ductal cells, and islet cells, but absent from pancreatic exocrine cells. TBT exposure decreased the production of estradiol and triiodothyronine and elevated the concentration of testosterone, and resulted in a decrease of ER alpha expression and an elevation of AR in the pancreas measured by Western boltting. The results suggested that TBT inhibited the proliferation and induced the apoptosis of islet cells via multipathways, causing a decrease of relative islet area in the animals treated for 60 days, which could result in a disruption of glucose homeostasis. The different presence of ERs and AR between the islets and exocrine pancreas might be one of reasons causing different effects on cell proliferation

Effects of tributyltin on epididymal function and sperm maturation in mice

The effects of tributyltin (TBT) on sperm parameters and epididymal function were investigated following oral doses of 0.5, 5 and 50 mu g/kg every 3 days for 45 days to male KM mouse. The TBT-treated groups showed a significant decrease in sperm counts and a significant increase in sperm abnormality both in a dose-dependent manner. The expression of matrilysin (MMP7) transcript in epididymis of mice exposed to TBT was significantly decreased in 5 and 50 mu g/kg group. There was a dose-dependent decline trend in the acid phosphatase activity, which somewhat relates with the TBT-induced increase in sperm abnormality. Acrosin and lactate dehydrogenase-X isoenzyme (LDH-X) activities from the cauda epididymal spermatozoa showed a dose-dependent decrease in the TBT groups. The result indicates a suppression of essential sperm maturational processes that precede the penetration of the oocyte by the sperm, such as capacitation and acrosome reaction. These results suggest that TBT could cause a spermatotoxic effects, the decline of sperm count and quality caused by TBT suggests that this chemical could impair fertility in animals. (C) 2009 Elsevier B.V. All rights reserved.National Key Technology R&D Program of China [2007BAC27B02]; National Basic Research Program of China [2006CB504005

Chronic Exposure to Tributyltin Chloride Induces Pancreatic Islet Cell Apoptosis and Disrupts Glucose Homeostasis in Male Mice

It has been reported that organotin compounds such as triphenyltin or tributyltin (TBT) induce diabetes and insulin resistance. However, histopathological effects of organotin compounds on the Islets of Langerhans and exocrine pancreas are still unclear. In the present study, male KM mice were orally administered with TBT (0.5, 5, and 50 μg/kg) once every 3 days. The fasting plasma glucose levels significantly elevated, and the levels of serum insulin or glucagon decreased in the animals treated with TBT for 60 days. In animals treated for 45 days, the number of apoptotic cells in the islets and exocrine pancreas was elevated in a dose-dependent manner. The percentage of proliferating (PCNA-positive) cells was decreased in the islets, while it was increased in exocrine acinar cells. Immunohistochemistry analysis showed that estrogen receptor (ER) and androgen receptor (AR) were present in vascular endothelium, ductal cells, and islet cells, but absent from pancreatic exocrine cells. TBT exposure decreased the production of estradiol and triiodothyronine and elevated the concentration of testosterone, and resulted in a decrease of ERα expression and an elevation of AR in the pancreas measured by Western boltting. The results suggested that TBT inhibited the proliferation and induced the apoptosis of islet cells via multipathways, causing a decrease of relative islet area in the animals treated for 60 days, which could result in a disruption of glucose homeostasis. The different presence of ERs and AR between the islets and exocrine pancreas might be one of reasons causing different effects on cell proliferation