L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise), Kyiv, Ukraine

ABSTRACT. When exposed to the body, pesticides and plant growth regulators (PGRs) can cause oxidative stress, intensify lipid peroxidation, change the activity of a number of enzymes, which can lead to disruption of the functions of various organs and systems of the body under a long-term exposure. In the agricultural practices of Ukraine, PGRs based on methyl derivatives of pyridine N-oxide are widely applied; the mechanisms of their toxic action have not yet been sufficiently studied, in particular, the effect on the morphofunctional state of kidneys. Therefore, finding out the functional state of kidneys under the exposure to methyl derivatives of pyridine N-oxide of is an urgent task for the development of preventive measures aimed at preventing the negative effects of xenobiotics on human health.
Aim. To study the morphofunctional state of kidneys under acute oral exposure to the plant growth regulator 2.6-Dimethylpyridine Noxide (Ivin).
Materials and Мethods. The research was conducted on sexually mature male Wistar Han (SPF) rats. 2.6-Dimethylpyridine N-oxide (Ivin), 99.9% was administered orally, at a single dose in the form of an aqueous solution (5 animals in a group) at doses of 650 mg/kg and 13 mg/kg, which corresponds to 1/2 and 1/100 LD50. The control group received distilled water at the same volume as the experimental groups. The clinical condition of the animals, body weight and body weight gain, absolute and relative weight of the kidneys, indicators characterizing the functional state of the kidneys were researched, macroscopic and histological examination of kidney tissues was performed.
The results. Under the exposure to Ivin at a dose of 650 mg/kg on the 7th day a decrease in body weight and weight gain, in the absolute weight of the kidneys, and an increase in the pH level of urine were observed. At a dose of 13 mg/kg, Ivin caused a slight but probable increase in the content of urea in the blood serum on the 1st and 7th day, a tendency towards a decrease in the content of urea and urea nitrogen in the urine has been observed on the 1st day of the research. A tendency towards an increase in creatinine clearance was registered at a dose of 13 mg/kg after the 1st and 7th days, and at a dose of 630 mg/kg on the 1st day of the research. No toxicologically significant macroscopic and histological changes in kidney tissues were registered.
Conclusions. Under the acute oral exposure to the body at the maximum tested dose (650 mg/kg), Ivin has a general toxic effect on the body of male rats, which is manifested by a decrease in body weight and absolute kidney weight, and a decrease in body weight gain. Ivin at the investigated doses does not cause toxicologically significant disruptions of kidney functions in male rats. A slight increase in urea in the blood serum while preserving the functional activity of the kidneys can indicate an increase in protein metabolism, and a tendency towards an increase in creatinine clearance indicates an intensification of glomerular filtration in the kidneys aimed at homeostasis stabilizing. Morphological changes in kidney tissues of rats are mainly characterised by mild or moderate blood plethora in the corticomedullary zone and in the medulla, which are not specific manifestations of the toxic effect of Ivin, since the specified effects are also manifested in the control group of animals.
Keywords: plant growth regulator, 2.6-Dimethylpyridine N-oxide, morphofunctional state of kidneys.

СПИСОК ВИКОРИСТАНИХ ДЖЕРЕЛ/REFERENCES

1. DSouza UJA. Pesticide toxicity and oxidative stress: a review. Borneo Journal of Medical Sciences. 2017;11(2):3-13. DOI: 10.51200/bjms.v11i2.466.

2. Пельо ІМ, Бардов ВГ, Омельчук СТ, Сасінович ЛМ. Кумулятивні властивості та характер токсикодинаміки сумішей пестицидів, що застосовуються в овочівництві. Современные Проблемы Токсикологии. 2010;4:19–28. [Pelyo IM, Bardov VG, Omelchuk ST, Sasinovych LM. Cumulative properties and nature of toxicodynamics of pesticide mixtures used in vegetable growing. Modern problems of toxicology. 2010;4:19–28].

3. Lushchak VI, Matviishyn NM, Husak VV, Storey JV, Storey KB. Pesticide toxicity: a mechanistic approach. EXCLI Journal, 2018;17:1101-36. DOI: 10.17179/excli2018-1710.

4. Tuychieva D, Mirkhamidova P, Babakhanova D, Parpieva M, Alimova R. Influence of pesticides on the activity of some enzymes of rat liver and ways of their correction. Norwegian Journal of development of the International Science. 2020;45(2):8-14.

5. Васецька ОП, Жмінько ПГ. Біологічна активність і токсикологічні властивості регуляторів росту рослин – метильних похідних піридин-N-оксиду. Синтез і біоактивність функціоналізованих азотовмісних гетероциклів, за ред. А.І. Вовка. Київ: Інтерсервіс; 2021. C. 288–324. [Vasetska OP, Zhminko PG. Biological activity and toxicological properties of growth regulators of plants – methyl derivatives of N-oxide pyridine. Book: Synthesis and bioactivity of functionalized nitrogen-containing heterocycles, Eds. A.I. Vovk. Kyiv: Interservice; 2021. С. 288–324].

6. Von Hendy-Willson VE, Pressler BM. An overview of glomerular filtration rate testing in dogs and cats. The Veterinary Journal. 2011;188(2):156–65. DOI: 10.1016/j.tvjl.2010.05.006.

7. Sandilands EA, Dhaun N, Dear JW, et al. Measurement of renal function in patients with chronic kidney disease. British journal of clinical pharmacology. 2013; 76(4):504– 15. DOI: 10.1111/ bcp.1219.

8. Горальський ЛП, Хомич ВГ, Кононський ОІ. Основи гістологічної техніки і морфофункціональні методи досліджень у нормі та при патології. Житомир: Полісся, 2015. 286 с. [Horalskyi LP, Khomych VG, Kononskyi OI. Basics of histological technique and morphofunctional research methods in normal and pathological conditions. Zhytomyr:Polissya, 2015. 286 p.].

Стаття надійшла до редакції 24 червня 2024 р.

The article was received by the editors 06.24.2024