Forty years of helminth biochemistry

Barrett, John

doi:10.1017/s003118200900568x

Cited by 39 publications

(25 citation statements)

References 71 publications

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“…Although metabolism of drugs has been extensively studied in mammals, the extent to which drugs are metabolized in nematodes remains to be determined [9,35,36]. Consequently we have investigated the metabolic pathway of TBZ in C. elegans and its regulation.…”

Section: Discussionmentioning

confidence: 99%

NHR-176 regulates cyp-35d1 to control hydroxylation-dependent metabolism of thiabendazole in Caenorhabditis elegans

Jones

Flemming

Urwin

2015

Biochemical Journal

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Knowledge of how drugs are metabolized and excreted is an essential component of understanding their fate within and among target and non-target organisms. Thiabendazole (TBZ) was the first benzimidazole (BZ) to be commercially available and remains one of the most important anthelmintic drugs for medical and veterinary use. We have characterized how Caenorhabditis elegans metabolizes and excretes TBZ. We have shown that TBZ directly binds to the nuclear hormone receptor (NHR)-176 and that this receptor is required for the induction by TBZ of the cytochrome P450 (CYP) encoded by cyp-35d1. Further, RNAi inhibition of cyp-35d1 in animals exposed to TBZ causes a reduction in the quantity of a hydroxylated TBZ metabolite and its glucose conjugate that is detected in C. elegans tissue by HPLC. This final metabolite is unique to nematodes and we also identify two P-glycoproteins (PGPs) necessary for its excretion. Finally, we have shown that inhibiting the metabolism we describe increases the susceptibility of C. elegans to TBZ in wild-type and in resistant genetic backgrounds.

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Section: Discussionmentioning

confidence: 99%

NHR-176 regulates cyp-35d1 to control hydroxylation-dependent metabolism of thiabendazole in Caenorhabditis elegans

Jones

Flemming

Urwin

2015

Biochemical Journal

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“…6,7 Adult male and female worms live much of this time in copula , the slender female fitted into the gynaecophoric canal of the male, where she produces eggs and he fertilises them (appendix). Adult worms digest erythrocytes and although most of their energy is obtained by glucose metabolism, 8,9 egg production is dependent on fatty acid oxidation 10 —both glucose and fatty acids being derived from the host. They live within either the perivesicular ( S haematobium ) or mesenteric ( S mansoni , S japonicum , and others) venules.…”

Section: Introductionmentioning

confidence: 99%

Human schistosomiasis

et al. 2014

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Human schistosomiasis—or bilharzia—is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination.

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“…Hymenolepis diminuta invasion leads to oxidative stress in small intestine of definitive host (Shin et al 2009). Reactive oxygen species (ROS) produced by host's organism during parasitic infestation, mediate interactions between host and parasite (Dzik 2006, Barrett 2009). Many parasitic helminths may survive in host body for a very long period of time due to their high degree of antioxidant enzymes activity (Dzik 2006, Chiumiento andBruschi 2009).…”

Section: Introductionmentioning

confidence: 99%

The antioxidant defence mechanisms of parasite and host after chronic Hymenolepis diminuta infestation of the rat

Hanna¹,

Skrzycki²,

Majewska-Wierzbicka³

et al. 2013

Polish Journal of Veterinary Sciences

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The aim of the present study was to determine antioxidant defence mechanisms in the rat and Hymenolepis diminuta after long-term infestation. We determined levels of oxidative stress markers, and activity of antioxidant enzymes in the rat small intestine and in particular parts of H. diminuta. Observed changes in antioxidant enzymes activity in H. diminuta and the rat intestine indicate the defence against parasitic infestation and probably allowed parasite to adapt and live in oxidative stress.

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Forty years of helminth biochemistry

Cited by 39 publications

References 71 publications

NHR-176 regulates cyp-35d1 to control hydroxylation-dependent metabolism of thiabendazole in Caenorhabditis elegans

NHR-176 regulates cyp-35d1 to control hydroxylation-dependent metabolism of thiabendazole in Caenorhabditis elegans

Human schistosomiasis

The antioxidant defence mechanisms of parasite and host after chronic Hymenolepis diminuta infestation of the rat

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