Dynamics of glutathione regulation in Schistosoma mansoni: correlations with the acute effects of oltipraz
Glutathione is present in adult Schistosoma mansoni (0.336 +/- 0.012 nmol/mg protein) at significantly lower levels than uninfected host tissues (1.051 +/- 0.013 nmol/mg protein, liver; 0.627 +/- 0.013 nmol/mg protein, kidney). Host hepatic glutathione levels decline significantly during the course of infection, while renal cortical glutathione levels are unaffected. Of the enzymes regulating glutathione utilization, glutathione reductase in the male parasite exhibits a specific activity of 10.3 +/- 4.2 nmol/mg protein, 15% of hepatic values. The apparent glutathione S-transferase activity was 26 +/- 7 ..mu..mol conjugate formed/min/mg protein with p-nitrobenzyl chloride as substrate (13% of hepatic values) and 526 +/- 18 ..mu..mol conjugate formed/min/mg protein with 1-chloro-2,4-dinitrobenzene as substrate (43% of hepatic values). Male schistosomes exhibited negligible glutathione peroxidase activity. Oltipraz, an antischistosomal compound, effected a significant depletion of parasite and host glutathione levels within 1 h of exposure in vivo and in vitro (at 250 mg/kg and 10 ..mu..M, respectively). Host tissue glutathionine levels returned to, or above, control levels by 6 h after oltipraz administration, while parasite glutathione levels remained significantly depressed. Uptake of (/sup 35/S) cysteine or (/sup 35/S) cystine by schistosomes was inhibited by oltipraz. However, the drug did not alter the relative distribution of label once incorporated into the parasite, indicating that the enzymes of glutathione synthesis were not directly inhibited.
- Research Organization:
- Michigan State Univ., East Lansing (USA)
- OSTI ID:
- 5151347
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
GLUTATHIONE
BIOCHEMICAL REACTION KINETICS
OXIDOREDUCTASES
ENZYME ACTIVITY
PESTICIDES
BIOLOGICAL EFFECTS
TRANSFERASES
CYSTEINE
CYSTINE
KIDNEYS
LIVER
SCHISTOSOMA
AMINO ACIDS
BODY
CARBOXYLIC ACIDS
DIGESTIVE SYSTEM
DISULFIDES
DRUGS
ENZYMES
GLANDS
HELMINTHS
KINETICS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PEPTIDES
PLATYHELMINTHS
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
THIOLS
TREMATODES
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