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Life Sci ; 103(2): 73-8, 2014 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-24727238

RESUMEN

AIM: Lobeline is a natural alkaloid derived from Lobelia inflata that has been investigated as a clinical candidate for the treatment of alcoholism. In a pre-clinical trial, lobeline decreased the preference for and consumption of ethanol, due to the modulation of the nicotinic acetylcholine receptor. However, the interaction between lobeline and ethanol is poorly known and thus there are safety concerns. The present study was conducted to evaluate the mutagenic and genotoxic effects of lobeline and assess its modulation of ethanol-induced toxicological effects. MAIN METHODS: CF-1 male mice were divided into five groups. Groups received an intraperitoneal injection of saline solution, lobeline (5 or 10mg/kg), ethanol (2.5 g/kg), or lobeline plus ethanol, once a day for three consecutive days. Genotoxicity was evaluated in peripheral blood using the alkaline comet assay. The mutagenicity was evaluated using both Salmonella/microsome assay in TA1535, TA97a, TA98, TA100, and TA102 Salmonella typhimurium strains and the micronucleus test in bone marrow. Possible liver and kidney injuries were evaluated using biochemical analysis. KEY FINDINGS: Lobeline did not show genotoxic or mutagenic effects and did not increase the ethanol-induced genotoxic effects in blood. Lobeline also protected blood cells against oxidative damage induced by hydrogen peroxide. Biochemical parameters were not altered, indicating no liver or kidney injuries or alterations in lipid and carbohydrate metabolisms. SIGNIFICANCE: These findings suggest that lobeline does not induce gene or chromosomal mutations, and that this lack of genetic toxicity is maintained in the presence of ethanol, providing further evidence of the safety of this drug to treat alcohol dependence.


Asunto(s)
Etanol/toxicidad , Inestabilidad Genómica/efectos de los fármacos , Inestabilidad Genómica/genética , Lobelina/toxicidad , Alcoholismo/diagnóstico , Alcoholismo/tratamiento farmacológico , Animales , Evaluación Preclínica de Medicamentos/métodos , Lobelina/farmacología , Lobelina/uso terapéutico , Masculino , Ratones , Pruebas de Mutagenicidad/métodos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/toxicidad , Distribución Aleatoria
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