RESUMEN
The development of plant-derived cysteine proteinases, such as those in papaya latex, as novel anthelmintics requires that the variables affecting efficacy be fully evaluated. Here, we conducted two experiments, the first to test for any effect of host sex and the second to determine whether the intensity of the worm burden carried by mice would influence efficacy. In both experiments, we used the standard C3H mouse reference strain in which papaya latex supernatant (PLS) consistently shows >80 % reduction in Heligmosomoides bakeri worm burdens, but to broaden the perspective, we also included for comparison mice of other strains that are known to respond more poorly to treatment with papaya latex. Our results confirmed that there is a strong genetic influence affecting efficacy of PLS in removing adult worm burdens. However, there was no effect of host sex on efficacy (C3H and NIH) and no effect of infection intensity (C3H and BALB/c). These results offer optimism that plant-derived cysteine proteinases (CPs), such as these from papaya latex, can function as effective anthelmintics, with neither host sex nor infection intensity presenting further hurdles to impede their development for future medicinal and veterinary usage.
Asunto(s)
Antihelmínticos/administración & dosificación , Carica/química , Proteasas de Cisteína/administración & dosificación , Látex/administración & dosificación , Nematospiroides/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Proteínas de Plantas/administración & dosificación , Infecciones por Strongylida/tratamiento farmacológico , Animales , Antihelmínticos/química , Proteasas de Cisteína/química , Femenino , Látex/química , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Nematospiroides/fisiología , Extractos Vegetales/química , Proteínas de Plantas/química , Infecciones por Strongylida/parasitología , Resultado del TratamientoRESUMEN
Eight strains of mice, of contrasting genotypes, infected with Heligmosomoides bakeri were studied to determine whether the anthelmintic efficacy of papaya latex varied between inbred mouse strains and therefore whether there is an underlying genetic influence on the effectiveness of removing the intestinal nematode. Infected mice were treated with 330 nmol of crude papaya latex or with 240 nmol of papaya latex supernatant (PLS). Wide variation of response between different mouse strains was detected. Treatment was most effective in C3H (90·5-99·3% reduction in worm counts) and least effective in CD1 and BALB/c strains (36·0 and 40·5%, respectively). Cimetidine treatment did not improve anthelmintic efficacy of PLS in a poor drug responder mouse strain. Trypsin activity, pH and PLS activity did not differ significantly along the length of the gastro-intestinal (GI) tract between poor (BALB/c) and high (C3H) drug responder mouse strains. Our data indicate that there is a genetic component explaining between-mouse variation in the efficacy of a standard dose of PLS in removing worms, and therefore warrant some caution in developing this therapy for wider scale use in the livestock industry, and even in human medicine.