Vlasenko E.K., Sychik S.I., Stelmakh V.A., Ilyukova I.I., Grynchak V.A.
The evaluation of white rats’ biochemical status on the impact of 5-aminolevulinic acid hexyl ester in subchronic experiment
Republican Unitary Enterprise «Practical-Scientific Centre of Hygiene», Minsk, Republic of Belarus
Vestnik VGMU. 2015;14(6):104-111.
Abstract.
Biochemical parameters of white rats’ status were studied in subchronic experiment during which they received perorally an active substance of the new plant growth regulator - 5-aminolevulinic acid hexyl ester. In the context of the thirty-days’ experiment the drug showed marked dose-dependent effects of cumulative properties manifestation at the level of lethal outcomes. Thus, during the experiment at the doses of 440 and 110 mg/kg no death of the experimental animals and in the control groups was observed. The introduction of the drug at the dose of 880 mg/kg (1/10 of DL50ac) led to the death of one animal, and at the dose of 1760 mg/kg (1/5 of DL50ac) resulted in the death of 7 rats out of 10. On the 30th day of the experiment several laboratory parameters of blood serum and urine were studied in rats. Intragastric administration of the drug to white rats led to the change in a number of laboratory biochemical parameters of the liver function, which was reflected in an increase of the activity of alanine aminotransferase and gamma glutamyltranspeptidase, reduction of de Rytis coefficient, a dose-dependent increase in the level of bilirubin was also observed. In the animals treated with the drug at the maximally tolerated dose of 440 mg/kg functional state of the liver monooxygenases was studied. The introduction of the drug led to the 1,4-fold increase of the specific content of cytochrome P450 with the similar 1,5-fold increase in the specific activity of the P450-reductase when compared to control values. In the liver of experimental animals the accumulation of cytochrome P420 was observed. As a result of studying the catalytic activity of cytochrome P450, the drug turned out not to change the Vmax and Km in reactions of O-dealkylation of 7-ethoxycumarine and 7-ethoxyresorufine therefore it does not affect the detoxification function of the liver. In general, changes in biochemical parameters (including those characterizing the state of monooxygenase system) in experimental animals treated with the studied substance in the subchronic experiment may indicate membranе damaging effects of the drug.
Key words: 5-aminolevulinic acid hexyl ester, toxicity, subchronic toxicity, cytochrome P450.
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