Avaliação da toxicidade aguda do complexo ni(ii)-melofen vi em camundongos swiss fêmeas

Abstract

The formation of metal complexes with transition metals, such as nickel, has aroused interest in biomedical research, especially due to their promising pharmacological properties, including antibacterial, antifungal, antitumor and anti-inflammatory activities. An important study to investigate new molecules is the toxicity test, with the acute toxicity study being the first performed because it allows the determination of defined exposure ranges where lethality is expected. The Organization for Economic Cooperation and Development (OECD), in guideline 423, establishes the acute toxicity protocol with the objective of observing the manifestation of possible toxic effects of a substance, providing subsidies regarding health risks after a short-term exposure assessment. The toxicological evaluation is performed through biological tests in animals and the results are extrapolated to humans and other animals. This study aimed to evaluate the acute toxicity of the metal complex Ni(II)-Melofen VI in female Swiss mice, according to guideline 423 of the Organization for Economic Cooperation and Development (OECD). Fifteen female Swiss mice were used for this purpose and distributed into five experimental groups, in which single doses of the ligand or the metal complex were administered via oral gavage at doses of 300 and 2,000 mg/kg. The parameters analyzed included the evaluation of acute toxicity, body weight variation, water and food consumption, verification of the wet weight of the organs, in addition to macroscopic and histological analysis of the liver, kidneys, spleen, lungs and heart. The results indicated significant toxicity of the Ni(II)-Melofen VI complex at a dose of 2,000 mg/kg, with 100% mortality and histopathological alterations in the lungs, liver and kidneys. At a dose of 300 mg/kg, mortality was 50%. On the other hand, the ligand alone did not show significant toxicity at any of the doses tested. Statistical analysis confirmed significant differences in the survival rate between the groups. However, when observing body weight gain, water and food consumption, and organ weight, the experimental groups did not show statistically significant differences between the groups analyzed. Regarding the macroscopic analysis, a consistent pattern similar to the control group was observed for the treated groups, with only the lung showing changes in color and texture in the metal complex groups at both doses. The microscopic analysis indicated histological changes in all organs evaluated for the metal complex groups at the high dose and at the lowest dose in the animal that died before the end of the experimental period. However, the organs of the animals in the complex ligand groups and the surviving animal of the metal complex at the dose of 300 mg/kg showed histological findings similar to the control group. Therefore, it is concluded that the Ni(II)-Melofen VI complex presents dose-dependent toxicity, while the complex ligand did not show signs of toxicity.