IRREVERSIBILITY OF ANTIANDROGENIC EFFECT OF LAMBDA-CYHALOTHRIN AFTER THE RECOVERY PERIOD IN THE STUDY ON MALE WISTAR HAN RATS

Prodanchuk N. G., Shepelskaya N. R., Kolianchuk Y. V., Evtushenko T. V.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Previously conducted studies showed endocrine-disruptor properties of pyrethroids when exposed to mammals, causing disturbances in the reproductive system. The purpose of these studies was to identify the hazard of lambda cyhalothrin (LCT) reproductive toxicity, as well as to study the reversibility and/or irreversibility of the resulting damage during the recovery period. Research methods. Lambda-cyhalothrin 98.06% of purity was administered ex tempore daily, except Saturday and Sunday, by oral gavage to three groups of animals in doses 0,3; 3,0 and 10 mg/kg of body weight for 11 weeks. After the expiry of the exposure period, part of the males was selected to study the parameters of sperm and blood serum testosterone levels, while the remaining males were used for a recovery period without exposure for one full cycle of spermatogenesis (70 days). Morpho-functional indicators of the gonad state and the level of total testosterone in the blood serum were studied in all males after exposure and recovery period. The total amount and the absolute and relative number of motile sperm were determined, the percent of sperm abnormal forms was calculated. Morphometric parameters of testes and epididymis were recorded. Results. Investigated LCT causes antiandrogenic effect which characterized by impaired of spermatogenesis and oligospermia, as well as a change in the testosterone content in the blood serum of experimental animals compared to the control. Dose dependence of the severity of oligospermia and spermatozoa adynamia is linear in nature both before and after the recovery period, increasing markedly at the end of the recovery period. While the response level of testosterone to increase of the dose is non-monotonic.The most pronounced statistically significant (P <0.01) decrease in the level of testosterone relative to the control is noted at the end of exposure at the dose of 3.0 mg/kg of body weight. When exposed to the minimum and maximum doses, there is a tendency for this parameter to decrease as compared with the control. After the recovery period, the minimum and maximum doses cause the tendency to increase in testosterone compared with the control, while the middle dose of LCT, significantly (P <0.05) induces a decrease in the content of this hormone relative to the control. The analysis of the qualitative and quantitative characteristics of the observed effects at the end of the exposure and recovery periods allows to presume that the tested LCT is irreversible xeno-agonists of estrogenic receptors with an intermediate degree of activity, causing damage to Sertoli cells and the spermogonial population of the germinative cells, depending on the dose level of exposure. The parameters characterizing the processes of spermatogenesis, and the testosterone content did not reach the control level during the recovery period, this indicates the irreversibility of the antiandrogenic effect for 10 weeks, and possibly the complete irreversibility of the observed effects. The systemic toxic effect, induced by the maximum dose tested and characterized by a decrease in the animals body weight, is reversible. Within the studied range of doses in the experiment on the males of Wistar Han rats, no-observed effect level (NOEL) of LCT is the dose of 0,3 mg/kg of body weight, the low-observed effect level (LOEL) is 3 mg/kg of body weight. Maximum tolerated dose is 10 mg/kg of body weight. Conclusions. The test system for the gonadotoxic activity identification is an adequate, highly sensitive methodological approach for testing the toxic effects of endocrine-disruptors.

lambda-cygalothrin, Wistar rats, anti-androgenic effect, recovery period, irreversibility

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«Bulletin of problems biology and medicine» Issue 4 Part 2 (147), 2018 year, 173-181 pages, index UDK 615.9:632.95:612.6:591.16

10.29254/2077-4214-2018-4-2-147-173-181