The functional state of the liver during a single oral influence on the organism of some of n-oxide pyridine methyl derivatives

Abstract

RESUME. Pesticides occupy one of the priority places among environmental pollutants. The hepatobiliary system disorder is a characteristic of most pesticides. The hepatotoxic effect of synthetic plant growth regulators (PGRs) based on pyridine N-oxide isn’t explored enough. The hepatotoxic effect PGR nature finding is an important aspect of preventive toxicology. Aim. To study the effect of some pyridine-N-oxide methyl derivatives on the liver functional state under a single oral dosage into the body. Materials and Methods. For the research were used PGRs – 2.6-dimethylpyridine-N-oxide (Ivin), 99.9 % and complex 2.6- dimethylpyridine-N-oxide with succinic acid (Poteitin), 99.9 %. During the experiment which was carried out on male Wistar Han rats, it was a single oral administration of aqueous solution form of test substances: Ivin in doses of 650 and 13 mg/kg and Poteitin in doses 1150 and 23 mg/kg. The activity of the alanineaminotransferase (ALT), aspartateaminotransferase (AST), alkaline phosphatase (ALP), the content of total proteins, glucose, triglycerides, cholesterol, urea and creatinine in the blood serum were determined on the 1st, 3rd, and 7th day using “Filisit- Diagnostics” reagent kit. EPR signals (g-2.25; g-2.14; g-2.05; g-2.03; g-2.00; g-1.97; g-1.94) were determined in liver tissue on the radio spectrophotometer “Varian E-109” (USA) at a temperature of 77 K. The results. Ivin at a dose of 13 mg/kg in particular study periods significantly increased the content of urea and glucose. At a dose of 650 mg/kg, the activity of AST, the content of urea, creatinine, and glucose significantly increased, and the activity of ALP decreased. Poteitin in a dose of 23 mg/kg in particular study times significantly increased the content of urea and creatinine, and the activity of ALP in the blood serum. At a dose of 1150 mg/kg, a significant decrease in the activity of ALP, and an increase in the content of urea, creatinine and glucose in the blood serum were revealed. The majority of liver EPR signals were reduced due to the influence of Ivin and Poteitin in both studied doses in different terms. Ivin at a dose of 13 mg/kg decreased the content of Mo7+-containing proteins and free radicals (FR) on 1st and 7th days respectively. At a dose of 650 mg/kg increased the content of iron-sulfur proteins (ISP) in 1stday of experiment and there was a decrease in the content of cytochrome P-450 (CytP-450), nitrosyl complexes, ISP and free radicals (FR) in 7 days. Poteitin at a dose of 23 mg/kg decreased the content of cyt-P-450, FR, ISP, and Mo7+–containing proteins, and increased the content of Cu2+-containing proteins. At a dose of 1150 mg/kg, there was a decrease in the content of cyt-P-450, BP, and ISP (for 1st and 3th days) and their increase for 7 days. Conclusions. With acute oral exposure, Ivin and Poteitin show a weak hepatotropic effect, characterized by a hyperglycemia, a slight decrease in the activity of alkaline phosphatase and an increase in urea and creatinine levels in the blood serum. Hyperglycemia can be associated with a stressogenic reaction to a chemical factor. This may indicate a carbohydrate metabolism disorders and various pathological conditions with long-term exposure to the studied substances. Intensification of the protein degradation and the accumulation of urea and creatinine in the blood serum can lead to a disorder of the filtering and excretory functions of the kidneys, which requires further research and clarification. Ivin and Poteitin reduce the EPR spectra of rat liver – cyt-P-450, free radicals, iron-sulfur proteins, nitrosyl complexes of non-heme iron, which indicates a decrease in the activity of the monooxygenase system, inhibition of oxidation processes, the formation disruption of iron-sulfur complexes and a decrease in the labile nitrosyl complex formation. A decrease in the content of Mo7+-containing proteins and an increase in the content of Cu2+-containing proteins may be associated with the activation of antiradical processes in the liver of rats. Key Words: plant growth regulators, Ivin, Poteitin, hepatotoxic effect, liver EPR spectra.