| Objective: As a typical environmental endocrine disruptor, nonylphenol (NP)could act as estrogen and affect the endocrine system, resulting in hormone synthesis,secretion, transport, binding and so on. As a matter of fact, the harmful effects of NPhave been studied for years, especially extensively identified and studied estrogen-likeeffect which causes a significant threat to normal reproduction and development. At thesame time, many scholars launched studies on its immunotoxicity, neurotoxicity et. al.NP is a typical environmental endocrine disruptor; its impact on the endocrine system isvery prominent. Recently, many scholars have focused on the effects of NP on thepituitary, thymus, thyroid and other endocrine organs. However, few studies have beenpublished which focused on the theme of whether and how nonylphenol affects thefunction of the important endocrine gland-pancreas. No consistent research conclusionshave been achieved as yet. To address this issue, the effects of subchronic exposure ofNP on pancreatic function were studied. And the impact of NP on glucose metabolismand the possible mechanism of the impairment of NP on pancreatic function werediscussed in combination with the related indicators.Method: Thirty-two SPF male SD rats (80-90days) were randomly divided intofour groups, eight rats of each group. All rats treated with NP through gavage at thedoses of0,40,100and250mg/kg respectively, once two days for90days. During theexperiment, the general condition of the rats was observed. The body weight of each ratwas measured every other day. The blood glucose was monitored regularly. After therats were anesthetized, the abdominal aorta blood was collected. Serum insulin,hexokinase and free fatty acid were evaluated using enzyme-linked immunosorbentassay (ELISA), respectively. Major organs were separated, weighed and the organcoefficient was calculated. Hematoxylin-eosin staining was used to estimatehistopathological changes of pancreas. Caspase-3protein expression of pancreatic cellwas detected by immunohistochemical assay. The TUNEL assay was used to detect apoptosis of pancreatic cells.Results:(1) After exposure of NP, no significant difference in body weight wasfound among the four groups, but the growth rate of250mg/kg group was significantlylower than the other groups. During exposure, no significant difference in daily foodintake was observed between the control and treated groups. In comparison with thecontrol group, daily water intake of the250mg/kg group was significant increased.(2)No significance was found in fasting plasma glucose of each group before and afterthe exposure. Fasting blood glucose of250mg/kg group was significantly higher thancontrol group only in the third time (ie, exposured42days).(3)Compared with thecontrol group, the pancreas weight of NP exposed groups did not change significantly.However, with the increasing dose of NP, pancreas coefficient remarkably decreased ina dose-dependent manner (r=-0.560, P<0.05).(4)Pathological examination showed nosignificant pathological alterations in the pancreas of rats from the NP-treated groupswhen compared with the control group, while less pancreatic islet number and smallerareas of the250mg/kg group was found.(5)With the increasing dose of nonylphenol,serum insulin levels were significantly reduced in a dose-dependent manner (r=-0.560,P <0.05). In comparison with the control group, the serum hexokinase in NP-treatedgroups was significantly decreased and the serum free fatty acids showed no significantdifference.(6)Compared with the control group, insulin sensitivity index (ISI)significantly increased in NP exposed groups, but insulin resistance index (IR) andpancreatic β-cell function index (HOMA-β) showed no significant difference amongfour groups.(7)Immunohistochemistry results showed that compared with the controlgroup, NP did not significantly change Caspase-3protein expression in pancreatic cells.(8)TUNEL assay showed no significant differences in the apoptosis level of pancreascells among the four groups.Conclusions:(1) NP exposure could significantly slow down weight gain in rats,suggesting that NP could affect normal growth and development in rats. With theincreasing dose, pancreas weight decreased while no significant difference was foundamong the four groups. Pancreas coefficients in NP-treated groups significantlydecreased and a dose-response relationship was found, suggesting that NP can affect thegrowth of rat pancreas.(2)With the increasing dose of NP, serum insulin and hexokinaselevels were significantly reduced while ISI were increased, suggesting that NP cancause abnormal insulin secretion in rats.(3)Pathological examination revealed that NP can cause a certain injury on pancreatic, which may affect insulin secretion.(4)Immunohistochemical and TUNEL suggest that the effects of NP on pancreatic functionmay not be via apoptosis. Exposure of NP will damage the pancreas function; affect thenormal insulin secretion, but further study still need to be conducted to investigate theexact mechanisms. |
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