Efficacy of glutathione for treatment of fascioliasis. An investigation in the experimentally infested rat.
Liver fluke infection (Fasciola hepatica) depresses the drug-metabolizing capacity of the hepatic mixed function oxidase (MFO) and glucuronosyltransferase (GT) enzyme systems, throughout a free radicals mediated lipid peroxidation process. Glutathione (GSH, CAS 70-18-8) administered chronically (100 mg/kg i.p. once daily for 40 days) to experimentally infested rats from the onset to the maximal development of the infection (40th day), greatly reduced the damage to membrane lipids of the liver tissue (primary event of the disease), as judged by malonic dialdehyde (MDA) content (decreased by 80%) and diene conjugation absorption (delta E 1% value falls from 1.94 to 0.67). As a consequence, serum glutamate-oxaloacetate (GOT) and glutamate-pyruvate (GPT) transaminases levels, liver GSH and phospholipid (PL) contents, cytochrome P-450, NADPH-cytochrome-P-450 reductase and some typical cytochrome P-450-dependent activities (p-nitroanisole O-demethylase, aniline hydroxylase, as well as UDP-glucuronosyltransferase (GT) activity, all markedly affected in the acute stage of the disease, tend to recover to the control values. The efficacy of GSH in preventing the impairment of the hepatic drug metabolizing capacity was also demonstrated by using as substrate the widely employed flukicidal agent nitroxinil (3-iodo-4-hydroxy-5-nitrobenzonitrile). The in vitro cytochrome P-450-dependent nitroxinil detoxification (reduction to 3-iodo-4-hydroxy-5-aminobenzonitrile), drastically impaired in infested animals (-80%), is markedly restored (3-fold increase) in GSH-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Maffei Facino
R
R
Istituto Chimico Farmaceutico Tossicologico, Università di Milano, Italy.
Carini
M
M
Aldini
G
G
Ceserani
R
R
Casciarri
I
I
Cavalletti
E
E
Verderio
L
L
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005211:Fascioliasis / Q000188:drug therapy* / Q000469:parasitology; D014453:Glucuronosyltransferase / Q000378:metabolism; D005978:Glutathione / Q000627:therapeutic use*; D008658:Inactivation, Metabolic; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009611:Nitroxinil / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D008315:Malondialdehyde; D003577:Cytochrome P-450 Enzyme System; D009611:Nitroxinil; D006899:Mixed Function Oxygenases; D014453:Glucuronosyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione