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Toxicological,toxicokinetic and gastroprotective evaluation of the benzaldehyde semicarbazone
Institution:1. Laboratório de Toxicologia Experimental, Departamento de Análises Clínicas e Toxicológicas da Faculdade de Farmácia, Universidade Federal de Minas Gerais, Brazil;2. Laboratório de Patologia Comparada, Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil;3. Centro Bioanalítico de Medicamentos da Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Brazil;4. Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Brazil
Abstract:Benzaldehyde semicarbazone (BS) has presented positive results in several pharmacological models, including anticonvulsivant and anti-inflammatory models. The present study evaluated the preclinical toxicity (acute and subchronic), as well as the toxicokinetic and gastroprotective effects of BS against ethanol lesions. Oral doses of 300 and 2000 mg/kg were used in the preclinical acute toxicity study; 100, 200, and 300 mg/kg were used in both the subchronic toxicity evaluation and the gastric study; and 300 mg/kg was used in the toxicokinetic study. No impact from the dose of 300 mg/kg could be identified; while, one animal died at 2000 mg/kg in the acute toxicity test. In the subchronic toxicity test, changes in the biochemical parameters of the liver, as well as in the histopatological evaluation, demonstrated that BS is a hepatotoxic drug. BS proved to be effective for moderate and severe gastric lesions. In the toxicokinetics study, BS presented a low concentration and rapid plasma disappearance. Several results also indicate that BS is likely to be mostly eliminated from the liver and may well undergo a first-pass effect after oral absorption. It was impossible to estimate the noobserved-adverse-effect-levels (NOAEL) and lowest-observed-adverse-effect-levels (LOAEL) due to the presence of hepatotoxicity in all tested doses.
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