RESUMEN
Benzimidazoles are the most widely used compounds in chemotherapy of alveolar hydatid disease (AHD), but long-term administration is required to reach detectable plasma levels. N-Methoxycarbonyl N'-2-nitro 4-trifluoromethyl phenyl thiourea (2) was prepared as a potential prodrug of (5-trifluoromethyl-1H-benzimidazole-2-yl)-carbamic acid methyl ester. Biological effects of 2 were evaluated in gerbils (Meriones unguiculatus) against the causative agent of AHD, Echinococcus multilocularis metacestodes, through a transmission electron microscopy study. Significant morphological damage of tegument and protoscolices occurred after an 18-day treatment. The treatment of AHD by using the prodrug form of the benzimidazole deserves further study.
Asunto(s)
Antihelmínticos/farmacología , Bencimidazoles/farmacología , Echinococcus/efectos de los fármacos , Tiourea/análogos & derivados , Animales , Antihelmínticos/uso terapéutico , Bencimidazoles/uso terapéutico , Equinococosis/tratamiento farmacológico , Equinococosis/parasitología , Echinococcus/ultraestructura , Gerbillinae , Masculino , Profármacos , Tiourea/síntesis química , Tiourea/farmacologíaRESUMEN
Ethyl N-N-benzyl-methyl-oxamate is a N-substituted derivative of the oxamic acid, well-known as inhibitor of the lactate dehydrogenase activity. The biochemical and ultrastructural effects of this drug in Echinococcus multilocularis metacestodes and the repercussions in the livers of receptive host, Meriones unguiculatus, were investigated. This compound decreased the specific activity of the lactate dehydrogenase in the metacestodes and the host liver by 81 and 86.8%, respectively. This N-methyl compound has shown an important repercussion on the lactate dehydrogenase activity due to its greater lipophilicity and thus allows a better penetration of the molecule. In the host liver, a fall of the alkaline and acid phosphatases activity was observed. The glucose and glycogen concentrations were also decreased. The ultrastructural study provided an alteration of the tegument of the metacestodes and damages of the muscular system. The parenchyma was disorganized. In conclusion, these biochemical and ultrastructural data obtained with ethyl-N-N-benzyl-methyl oxamate in E. multilocularis metacestodes show clearly the importance of the lactate dehydrogenase activity in the metacestodes.
Asunto(s)
Aminoácidos/uso terapéutico , Equinococosis Hepática/tratamiento farmacológico , Echinococcus/efectos de los fármacos , Ácido Oxámico/uso terapéutico , Fosfatasa Ácida/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Glucemia/metabolismo , Fenómenos Químicos , Química , Equinococosis Hepática/enzimología , Equinococosis Hepática/parasitología , Echinococcus/ultraestructura , Femenino , Gerbillinae , L-Lactato Deshidrogenasa/metabolismo , Hígado/enzimología , Hígado/parasitología , Glucógeno Hepático/metabolismo , Masculino , Ácido Oxámico/análogos & derivados , Ácido Oxámico/análisisRESUMEN
A study on the biochemical and ultrastructural effects of isatin on Echinococcus multilocularis metacestodes in Meriones unguiculatus is reported. In the metacestode, after an 18 day treatment period, the alkaline phosphatase and lactate dehydrogenase activities decreased and the acid phosphatase activity increased. Glucose and glycogen stores declined significantly. Examinations of the ultrastructure revealed an increase of lysosomes and phagocytic reactions. The protoscolesces were damaged and an abnormal striated process appeared. The tegumental cytoplasmic syncytium remained unaltered. These observations suggest that isatin derivatives may have a role in the chemotherapy of infections caused by Echinococcus spp.