The study of acute toxicity of 1,3-oxazole-4-il-phosphonic acid derivative in intraperitoneal administration
Keywords:derivative of 1, 3-oxazole-4-yl-phosphonic acid, OVP-1, acute toxicity, intraperitoneal administration, mice, mid-lethal dose
The derivative of 1,3-oxazole-4-yl-phosphonic acid (OVP-1) has the vasodilatory activity and is studied as a potential antihypertensive agent. The toxicological assessment plays an important role in the preclinical study of new drugs.
Aim. To study the acute toxicity of OVP-1 in intraperitoneal administration and determine its average lethal dose.
Materials and methods. The intraperitoneal route of administration was chosen as it provides the systemic action of drugs. The experiment was conducted on female and male of white non-linear mice. Five experimental groups of animals corresponded to such dose levels of OVP-1 as 1000 mg/kg, 3000 mg/kg, 3500 mg/kg, 4000 mg/kg, and 4500 mg/kg. The solution of 1,3-oxazole-4-yl-phosphonic acid derivative and the blank solution (the mixture of Tween-80 and water for injection in the ratio of 1 : 10) was injected once in the abdominal cavity of mice. They were monitored for their mortality, behavior, and clinical characteristics over the following 14 days. LD50 of OVP-1 was determined by the number of dead animals before autopsy.
Results and discussion. As a result of the experiment the peculiarities of the toxic effect of 1,3-oxazole-4-yl-phosphonic acid derivative on the organism of the experimental mice have been studied. Based on clinical observations there were no changes in the behavior and appearance of mice for 14 days. However, taking into account the rare cases of tachypnea, piloerection and catalepsy, it can be assumed that OVP-1 in toxic doses can affect the central nervous system, the autonomic system, and there is a probability of occurrence of cardio-pulmonary insufficiency.
Conclusions. It has been determined that LD50 of OVP-1 derivative in intraperitoneal administration to mice of both sexes is 3350.67 ± 54.62 mg/kg and belongs to the toxicity class VI – relatively harmless compounds, which makes this compound promising for further preclinical pharmacological studies.
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