Protective effects of thiamine pyrophosphate and cinnamon against oxidative liver damage induced by an isoniazid and rifampicin combination in rats.
Efectos protectores del pirofosfato de tiamina y la canela contra el daño hepático oxidativo inducido por la combinación de isoniazida y rifampicina en ratas.
Resumen
Se ha demostrado que la isoniazida y la rifampicina (IRC) causan hepatotoxicidad tanto en estudios clínicos como preclínicos. El estrés oxidativo y la inflamación se han considerado responsables de la patogénesis de la hepatotoxicidad inducida por IRC. En estudios anteriores se han demostrado los efectos antioxidantes y antiinflamatorios del pirofosfato de tiamina (TPP) y del extracto de canela (CE). Por lo tanto, en nuestro estudio se investigaron los efectos protectores del TPP y el CE sobre el posible daño hepático causado por el tratamiento con IRC en ratas. Se clasificaron 24 ratas Wistar albinas en cuatro grupos: un grupo sano (HG), un grupo IRC (IRG), un grupo TPP+IRC (TIRG) y un grupo CE+IRC (CIRG). El TPP (25 mg/kg) se administró por vía intraperitoneal al TIRG, mientras que el CE (100 mg/kg) se administró por vía oral al CIRG. En IRG, TIRG y CIRG, se administró isoniazida (50 mg/kg) y rifampicina (50 mg/kg) por vía oral una hora después de estos tratamientos. Durante siete días, este procedimiento se repitió una vez al día. Tras este periodo, se tomaron muestras de sangre de las venas de la cola y se sacrificaron las ratas. Los tejidos hepáticos extraídos se analizaron en busca de citocinas oxidantes, antioxidantes y proinflamatorias y se sometieron a una evaluación histopatológica. También se midieron las actividades séricas de la alanina aminotransferasa y la aspartato aminotransferasa. Con el tratamiento con IRC se observó un aumento de los niveles de malondialdehído, factor nuclear kappa B, factor de necrosis tumoral alfa, interleucina 1 beta e interleucina 6, una disminución de los niveles totales de glutatión y de las actividades de superóxido dismutasa y catalasa, y un aumento de las actividades de alanina aminotransferasa y aspartato aminotransferasa (p<0,001). El análisis histopatológico del IRG sugirió hepatotoxicidad (p<0,001). El TPP y el CE administrados con el IRC inhibieron los cambios bioquímicos (p<0,001). En el TIRG, esta inhibición fue mayor que en el CIRG (p<0,05). El daño histoló-gico fue inhibido por el TPP (p<0,001). El CE previno los cambios bioquímicos pero no los histológicos, excepto la infiltración de células inflamatorias. Por lo tanto, TPP puede ser una mejor opción que CE para la prevención de la hepatotoxicidad inducida por IRC.
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