Studies On The Thyroid Disturbance Of Thiadiazole Fungicides In SD Rats

It is widely accepted that thyroid hormones play predominantly a nuclear roleand function in the growth and differentiation of many organs. Pesticide in THs hadthe greatest proportion. Due to thiadiazole compound's excellent bioactivities andvarious chemical structures, as well as the high activity and low toxicity, it isbecoming a new research hotspot for more and more scientists. In the present study,we used the pubertal female rat assay to detect the effect of bismerthiazol, saisentongand thiodiazole-copper on thyroid function in the intact juvenile female rat. We haveexamined the effect of these pesticides on several thyroid endpoints: serum hormoneconcentrations, thyroid gland weights, hyperplasia of thyroid follicular cells, as wellas hepatic microsome enzyme activities of thyroid metabolism. The disturbance effectand possible action mechanism were studied, which will provide scientific basis forrisk management of these compounds. The main results and conclusions are asfollows:1,Pubertal female rats were exposed to three thiadiazole compounds(bismerthiazol, saisentong and thiodiazole-copper) at different dosages of 10, 20,40mg/kg, 5, 10, 15mg/kg and 4, 10, 20, 30mg/kg, respectively, by oral gavage andthe control group was administered with vehicle alone. After treatments, the rats weresacrificed. The results indicated that three thiadiazole compounds administration wereincreased thyroid gland weights.2,The serum triiodothyronine(T₃), thyroxine(T₄) and thyroid stimulatinghormone(TSH) concentrations were determined by ELISA kits. The results indicatedthat a statistically significant decrease in serum T₃ and T₄ was observed in allbismerthiazol groups, meanwhile, the TSH was increased significantly in allbismerthiazol treated groups. In saisentong groups, the surm T₃ was found decreasedsignificantly at dosage of 5 and 10mg/kg. Thiodiazole-copper administration weredecreased serum T₃, T₄ and increased surm TSH at the dosage of 20 and 30mg/kg. 3,In order to validate whether these pesticide have effect on the thyroid, thehistopathological examination was conducted based on the measurement of organweights and hormone. The results indicated all the group of bismerthiazol could haveeffect on the thyroid function significantly. The primary microscopic change of thethyroid follicular was diffuse hypertrophy and hyperplasia. There was no notablechange in the all saisentong treated groups. In all treated groups of thiodiazole-copper,the primary microscopic change of the thyroid gland was colloid depletion that wasoften associated with increased numbers of follicles in which lumens were decreasedin diameter and were devoid of colloid, though the dose of 4mg/kg/day inthiodiazole-copper did not be observed having effect on the thyroid function.4,The immunohistochemical of proliferating cell nuclear antigen on thyroidgland was studied in saisentong treatment groups to confirm whether saisentong haveeffect on the thyroid follicular cells. The result indicates that the dosage of 15mg/kg/dcould produce hyperplasia of thyroid follicular cells slightly, though this result is notstatistically significant for control groups, this finding may be biologicallymeaningful.5,Since UDPGT is an important hepatic enzyme that metabolizes T₄, helpingcharacterize possible biochemical mechanisms for thyroid hormone, the hepaticenzyme activity was tested at last. The results indicated the GST was restrained atdoses of 10, 20mg/kg/d and the UDPGT was induced at 10mg/kg/d in bismerthiazolgroups. In saisentong treated groups, the GST was restrained at doses of 10, 15mg/kg/d and the UDPGT was induced at dosage of 5, 10mg/kg/d. Thiodiazole-copperadministration were restrained GST and induced UDPGT at the same dosage of30mg/kg/d.6,The action mechanism of saisentong in disturbing thyroid may be different tobismerthiazol and thiodiazole-copper, which needs to be studied further.