ABSTRACT
Coumarin is an important class of natural organic compounds, which widely exists in a variety of plants and microorganisms. Coumarins have many biological activities and wide clinical applications, such as anti-tumor, anti-HIV, anti-bacterial, anti-inflammatory, anti-oxidation, anti-coagulation, but they have obvious toxic effects in rodents. It was found that the toxicity of coumarins in different animals and organs was significantly different, and high dose oral administration was more likely to produce toxic reactions. Based on the research and analysis of domestic and foreign literatures in recent 60 years, this paper mainly summarized the hepatotoxicity and pulmonary toxicity induced by coumarins, and probed into their possible mechanisms. It was found that the toxicity of coumarins had metabolic differences and species differences. The liver of rats and lungs of mice were more susceptible to coumarins. Toxic reactions occurred mainly in the second metabolic pathway of coumarin metabolism in vivo. In order to put forward safety considerations and evaluate the impact of coumarin on human body, it was found that coumarin is unlikely to produce hepatotoxicity at normal exposure level. It was also suggested that species differences due to different metabolic patterns in model animals should be carefully considered when assessing coumarin toxicity, in order to provide reference for clinical research and rational use of coumarins and improve the rational use of coumarins.
Subject(s)
Animals , Humans , Mice , Rats , Coumarins/toxicity , Liver/drug effects , Lung/drug effects , Metabolic Networks and Pathways , Species Specificity , Toxicity TestsABSTRACT
Avaliou-se o efeito imunotóxico causado por exposição a baixas doses de citrinina (2,5mg kg-1) em camundongos albinos expostos à micotoxina antes (n=15), durante (n=15) e após (n=15) a imunização com antígeno inerte, representado por eritrócitos de carneiro - sheep red blood cells (SRBC). Quinze camundongos foram usados como controle (não intoxicados). Sete dias após o tratamento, os animais foram sangrados e os títulos de anticorpos anti-SRBC e de complemento foram determinados. A citrinina diminuiu os títulos de anticorpos primários em todos os grupos intoxicados. A intoxicação antes e após a imunização provocou diminuição em 87,5 por cento nos títulos médios de anticorpos específicos. A exposição simultânea à imunização gerou diminuição de 75 por cento. Houve acentuada redução nos níveis de complemento circulante, detectada nos animais previamente intoxicados (93,8 por cento), ou intoxicados juntamente com a imunização (87,5 por cento).
Subject(s)
Animals , Citrinin/administration & dosage , Citrinin/adverse effects , Citrinin/toxicity , Coumarins/administration & dosage , Coumarins/toxicity , Immunosuppression Therapy , MiceABSTRACT
La ingestión de cumarínicos conduce a hipoprotrombinrmia y diátesis hemorrágica. Se presenta el caso de una paciente quien, después de ingerir una sobredosis de antiinflamatorio (Wobenzym-R), desarrolló hipoprotrombinemia grave, hematuria, sangrado de tubo digestivo y púrpura. La administración de plasma fresco y suplementos de vitamina K resolvió el cuadro en 24 horas. En conejos, se logró demostrar que el fármaco en cuestión era capaz de producir alargamiento del tiempo de protrombina, y en estudios cromatográfico pudo demostrarse un componente compatible con cumarina, por lo que se concluyó que el medicamento estaba posiblemente contaminado por este fármaco. Este informe debe alertar a la comunidad médica sobre la capacidad de este antiinflamatorio de producir hipoprotrombinemia grave