Impact of Prolonged Exposure to Pyrethroid Pesticides on Thyroid Function

online XXI : -2020

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.., . . ..................................................................................................25 . ., . . ................................................................................................................................. 28 Khalbaeva Makhlyo.. THE DIAGNOSIS AND TREATMENT MEASURES OF THE PEOPLE S DISEASE OF URINARY STONES IN THE ARAL SEA REGION.............................................................................................................30 PREGNANCY TACTICS, AND DIAGNOSTIC LYMPHOMAS: PREGNANCY TREATMENT Khodzhaeva F.T., MANAGEMENT PRINCIPLES .....................................................................................................32 AND Khodzhaeva F.T., MODERN METHODS OF EPILEPSY THERAPY IN WOMEN DURING PREGNANCY .................................................................. 34 Kholova Nargis Ravshanovna., Jonibekov J.J., ULTRASOUND RESEARCH OF THE STOMACH OF THE BORN .................................................................... 35 ACUTE Mukhtorov CORONARY PHARMACOEPIDEMIOLOGICAL ANALYSIS IN PATIENTS................. 38 Mukhriddin., Rakhmatova SYNDROME. Dilbar Bahriddinovna., STUDY OF Vaisov I.A Abbaskhanova F.X Khalitov I.I Khudaynazarova M.Kh., WITH PATHOGENETIC HORMONAL DISORDERS ............................................................................. 40 SIGNIFICANCE OF ACNE IN WOMEN Zokirova Nargiza Bahodirovna, Islomova Shohista Abdixalilovna. IMPACT OF PROLONGED EXPOSURE OF PIRETROID PESTICIDES ON THE THYROID FUNCTION OF THE OFFSPRING ......................................................................................................41 PREGNANT RATS AND THEIR 262

4. // . . 2002. 2. .22. 5. 10. . ., . . // . . 2002. 2. .22. 6. 11. . ., . . // . . 2002. 1. .40-41. 7. , . : . - .: - - , 2005. - 48 . 8. . . . 1. - .: , 2006. - 360 . . ., . . - IMPACT OF PROLONGED EXPOSURE OF PIRETROID PESTICIDES ON THE THYROID FUNCTION OF THE PREGNANT RATS AND THEIR OFFSPRING Zokirova N. B., Islomova Sh. A. Tashkent Pediatric Medical institute Tashkent, Uzbekistan Introduction. For two decades, the world's literature uses the term "endocrine-disrupting chemicals or endocrine disruptors (EDC or ED), adopted by the Agency for the U.S. Environmental Protection Agency in 1991. This term combines all the chemicals that in the organism of humans and animals change the processes of synthesis, secretion, transport, and metabolism of natural hormones and thereby lead to a disruption of hormonal homeostasis. There are more than one hundred pesticides of which 80% are commonly used as insecticides and fungicides, have different endocrine-disrupting effects. One of the most common representatives of the pyrethroids is lambda-cyhalothrin (LCT), which is a highly effective insecticide even at low doses and widely used in the home, agriculture and health worldwide. However, the endocrine - disrupting features of LCT has been identified recently and reports about them relatively few. If the endocrine- disrupting effect of LCT on the reproductive system can be considered proven, whereas the effect of LCT on the hypothalamic- pituitary- thyroid axis is not yet fully clear. It should be noted that all studies of the LCT on thyroid function were performed on adults and using relatively high doses of this pyrethroid. However, animals and humans are most sensitive to the action of pesticides in the embryonic and early postnatal periods of life. Moreover, the negative impact of these effects may occur no immediately, but after many years in the adult organism. It is now believed that to exposure of the endocrine-disrupting chemicals in utero or early childhood period is playing an important role in the pathogenesis of many diseases such as obesity, atherosclerosis, hypertension and coronary heart disease, cancer, reproductive pathology and others. In addition in real life the organisms, including pregnancy females and children, often subjected to prolonged exposure of low doses of pesticides or their metabolites. Unfortunately, the endocrine - disrupting 41

effects to exposure of LCT in utero and early childhood period are still virtually unknown. Based on the foregoing in the present work we have studied the effect of long-term exposure to low doses of lambda- cyhalothrin on the state of thyroid function of pregnant female rats and their offspring. Material and methods. Lambda-cyhalothrin as a 10% emulsion concentrate (trade name "Titan") received from the joint Uzbek-German Company "Euro- Team". Experiments were performed on white adult virgin female rats Wistar weighing 150-170 g and sexually mature male rats were used for fertilization. Then the female rats were divided into two groups of 45 rats each. The first (treated) group of rats was administered per os through gavage diluted in saline lambda- cyhalothrin at the rate of 8 mg / kg / day. The second (control) group in the same way received the same volume (0,4 ml/rat/day) of sterile saline. The administration of the LCT did not stop until the end of the experiments. On 31 day of experiments female rats of both groups were combined with male rats for fertilization. Pregnancy was monitored by the presence of sperm in vaginal smears. After becoming pregnant females separated from males and placed in separate cages for future research. The parts of both group pregnant females were sacrificed at 14 and 21 days of gestation (GD 14 and GD 21) under light ether anesthesia. Other rats were sacrificed in the same way at 14 and 21 days after birth (lactation day, LD 14 and LD 21). Offspring of females treated with LCT by the number and size did not significantly differ from controls. There are only a belated opening of the eyes and detachment of ears compared to control. Offspring from both groups of animals were sacrificed at 7, 14, 21 and 30 days (postnatal days, PND 7, PND 14, PND 21 and PND 30) after birth under light anesthesia with ether. After sacrificing blood was collected into dry sterile tubes without anticoagulant and the resulting serum was used to determine the concentration of hormones. The thyroxine (T4), triiodothyronine (T3) and thyroid-stimulating hormone (thyrotropin, TSH) in serum were measured by immunoassay using specific kits of "Human" (Germany) and the spectrophotometer "Singl" (Germany). Thyroxine, triiodothyronine were expressed in ng / ml, and thyroid-stimulating hormone was expressed as mIU / l. Calculation and statistical analysis was performed using the statistical package for Window`s. Statistical significance between control and treated values were compared using Student's LSD test and Pvalues less than 0.05 were considered significance. Results. The obtained data showed that the pregnancy, especially lactation by itself lead to a progressive increase of T4 and T3. In the female rats that administered during the month before pregnancy of LCT, the concentration of these hormones decreased slightly and not significantly different from controls. Consequently, the 30 day exposure of low doses LCT is not expressed the hypothyroidism in non-pregnant rats. Nevertheless, even a small decrease in T4 and T3 in these animals was accompanied by an increase in the concentration of TSH. With the onset of pregnancy in rats receiving LCT has developed a distinct hypothyroidism. At 14 and 21 days of gestation the concentration both of T4 and T3 were significantly lower compared with the control.Aparticularly large 42

difference between the LCT received and control rats has revealed at 14 and 21 days of the lactation. At these days the concentration of T4 and T3 in the LCT received rats on 1.3 - 1.4 times decreased compared with controls. The concentration of TSH of both groups of rats progressively increased from pregnancy to lactation. However, the level of this hormone in LCT treated rats on all days of pregnancy and lactation significantly exceeded the corresponding parameters of the control group. The exposure of L T in utero and through breast milk led to a significant breach of thyroid function in the offspring. The concentration both of T4 and T3 in LCT administered rats in all periods of the study were significantly decreased compared with controls. The biggest difference in the concentrations of hormones has found in 14 and 21 days of lactation, when the level of hormones in the LCT administered rats was reduced by more than 1.3 times compared with control. On day 30 of postnatal period the concentration of T4 and T3 in LCT received rats remained significantly lower compared with control. Determination of the concentration of the thyroid-stimulating hormone (TSH) showed its progressive increase on all days of the study. The maximum increase of TSH (to 1.7 time compared with control) was observed on 30 day after birth. Discussion. Our study showed a gradual increase in the levels of thyroxine (T4), triiodothyronine (T3 ) and thyroid-stimulating hormone (TSH) in all female rats during the pregnancy and lactation. It is known that during pregnancy the need for thyroid hormones (TH) increases by 30-50 % and the thyroid gland has to cope with this increased demand. This state may be a reflection of increasing the transfer of TH from pregnant females to their fetuses and / or more efficient production TH by the thyroid gland after birth. Our data support the view that the functioning of the hypothalamic- pituitary- thyroid axis of the maternal organism is a necessary condition for the natural development of the thyroid gland embryo and for prevention of various disorders in the postnatal period. On our data prolonged exposure to low doses of LCT had different effects on thyroid function of pregnant and non-pregnant female rats. We found that in non- pregnant female rats LCT exposure for 30 days resulted in a slight decrease of levels of the TH, but it significantly increased the concentration of TSH. In contrast, the impact of LCT in pregnant female rats and especially in lactating period led to a marked reduction in TH concentration with a significant increase in TSH levels. Thus, our data suggest an endocrine - disrupting, and more precisely, thyroid - disrupting effect of prolonged exposure to LCT during pregnancy and lactation. Without a doubt, the lack of TH in the maternal organism leads to violations of the growth and formation of various organs, primarily the nervous and endocrine systems in the embryonic and early postnatal periods. Unfortunately, data about the effect of prolonged exposure to LCT through maternal organism on the postnatal growth and development of the offspring, we However, a number of studies have shown that hypothyroidism in the maternal organism, caused by the action of some environmental toxicants such as dioxins leads to the development of neuro- endocrine disorders in the offspring. normal of the have not found. 43

We have found that prenatal and postnatal exposure to low doses of LCT significantly disturbed thyroid function in the offspring. The concentrations both of T4 and T3 in all periods of experiments in the offspring from LCT received rats decreased, while the TSH level was significantly higher than controls. Therefore, the LCT has a fairly pronounced thyroid-disrupting effect in the pregnant and its impact in the embryonic and early postnatal periods creates a risk for further growth and development of the child. The mechanism of thyroid-disruptor effect of the LCT, as well as other pyrethroide pesticides, has not yet fully understood. It is assumed that the reduction in thyroid hormones may be the result of enhanced its clearance by the liver enzymes or the result of a direct cytotoxic effect on the thyroid gland of toxic products of oxidative stress). Recently have been shown that pyrethroids, and especially, their metabolite 3-phenoxibenzoic acid (3- PBA), have high antagonist properties to the thyroid hormone (TH) receptors. There is also a perception that the action of endocrine-disrupting substances (EDs) is not fit into the classical scheme of hormone- dependent regulation and feedback and the effect of EDs is associated with a complex multitarget and multimodal actions on the hypothalamic- pituitary- thyroid axis. In our experiments, we did not explore the state of hormones of the hypothalamus, but this does not exclude the involvement of this particular link in the development of thyroid function failure when exposed to LCT. All this suggests that the mechanisms of disorders of thyroid function in pregnant females and their offspring exposed LCT remain complex and require further detailed studies. The results of these studies may help to prevent the adverse effects of environmental pollutants on the thyroid function of pregnant women and their children. Conclusion. Prior to pregnancy in female rats, effects of LCT for 30 days resulted in only a slight decrease in thyroid hormones thyroxine (T4) and triiodothyronine (T3) levels, but it significantly increased the concentration of thyroid-stimulating hormone (TSH). In contrast, the impact of LCT in pregnant, and especially in lactating rats, and also their offspring have led to a marked reduction in TH levels with a significant increase in TSH levels. Thus, the L T has a fairly pronounced thyroid - disrupting (TD) effect, which in non-pregnant female rats is shown to a small extent. The most pronounced TD effect of LCT in female rats and their offspring is manifested during pregnancy and lactation, which creates a risk for further growth and development of the child organism. Literature: 1. N.B.Zokirova. . // . - 2009. - 2. - . 69-71. 2. . . . // . - 2012. - 5. . 24-26. 3. Mnif W., Hassine A.I., Bouaziz A., Bartegi A., Thomas O., Roig B. Effect of Endocrine Disruptor Pesticides:AReview// Int. J. Environ. Res. Public Health., 2011. Vol. 8, pp. 2265 2303. 44

4. Prolonged Exposure of Low Doses of Lamda-cyhalothrin on the Thyroid Function of the Pregnant Rats and Their Offspring. //Medical and Health Science Journal 2012. - Vol. 13. - pp. 86-92. www.pradec.en 5. Tukhtaev K. R., Zokirova N. B., Tulemetov S. K., Tukhtaev N. K., Tillabaev M.R., Amirullaev O.K., Otajonova A. N., Yarieva O. O. Effect of Exposure of Low Doses of Fipronil on Thyroid Function of Pregnant Rats and Their Offspring. // The Internet Journal of Toxicology. 2013. Vol. 10. - N. 1. www.ispub.com /IJTO/10/1/14550. 6. Vandenberg L. N., Colborn T., Hayes T. B., Heindel J. J. et al. Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses. //Endocrine Reviews. -2012.- Vol. 33. - pp. 378-455. 7. N.B.Zokirova,N.A.Ruzieva. The effect of maternal exposure of pesticides on the postnatal development of the thyroid gland of offspring.-2020 Vol. 157. - N.2-3 pp.83-84/ Tukhtaev K. R., Zokirova N. B., Tulemetov S. K., Tukhtaev N. K. Effect of Prolonged 45