[
Trop Med Parasitol,
1989]
Fourteen synthetic retinoids with known and different binding affinities to retinol binding proteins of Dirofilaria immitis, retinol, and retinoic acid were tested in vitro against female Litomosoides carinii (drug levels 20, 10, 1 nM/ml) and against microfilariae of L. carinii, Brugia malayi, B. pahangi and Acanthocheilonema viteae (drug levels 100, 20, 10, 1 nM/ml). All compounds including retinol and retinoic acid had at least some effects on the filarial parasites. Except for 3 synthetic retinoids, continuous exposure of adult L. carinii to the drugs reduced the motility of the worms completely or remarkably by day 7 of incubation in a dose and time dependent fashion. Also, the release of microfilariae was completely or remarkably suppressed in a dose and time dependent manner by 20 and 10 nM/ml of all except 4 of the retinoids. Short term exposure to the drugs (up to 20 nM/ml) for 4 h followed by subsequent incubation in drug-free medium was ineffective except for one synthetic retinoid (13-cis-N-(2-hydroxyethyl)retinamide:13-cis-Her). Effects on microfilariae were also dose and time dependent. All compounds affected markedly the motility of L. carinii microfilariae within 20 h at dose levels of 1 nM/ml and above. Microfilariae of B. malayi, B. pahangi and especially of A. viteae were generally less sensitive. Eight of the synthetic retinoids, but not retinol and retinoic acid, were effective (10 nM/ml). There were generally no correlations between the various effects of individual compounds; i.e., activities varied within one species depending on the parameters used and depending on the parasite species.(ABSTRACT TRUNCATED AT 250 WORDS)
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Mol Biochem Parasitol,
2011]
The requirement of aerobic organisms to control damage caused by reactive oxygen species has led to the evolution of the antioxidant systems. Peroxiredoxins are a large family of peroxidases which detoxify hydrogen peroxide at the expense of thiols. The parasitic nematode Haemonchus contortus contains two peroxiredoxins, HcPrx1 a mitochondrial protein and HcPrx2 a cytoplasmic protein. Although both peroxiredoxins contain the conserved eukaryotic motifs 'GGLG' and 'YF', identified as critical for hydrogen peroxide instability, both were stable to high concentrations of hydrogen peroxide, demonstrating different functions to their mammalian counterparts. H. contortus also contains two thioredoxin reductases and five different thioredoxin-like proteins. The activity of both peroxiredoxins was specific for the thioredoxin system; however, both could also be regenerated by the glutathione system when coupled to the nematode specific thioredoxin HcTrx5. Analysis of homologous genes in Caenorhabditis elegans showed that only CePrx2, which is secreted, was sensitive to the external oxidant hydrogen peroxide. However, both peroxiredoxins KO C. elegans were sensitive to intracellular free radicals and both peroxiredoxins protected DNA from free radical attack. The results demonstrate that the hydrogen peroxide detoxification and the antioxidant activity of the peroxiredoxins are separate activities that are independent of the 'GGLG' and 'YF' motifs.