Author:
Hum Susan,Robitaille Line,Hoffer L. John
Abstract
Hepatic glutathione (GSH) plays an important role in the detoxification of reactive molecular intermediates. Because of evidence that the intrahepatic turnover of glutathione in the rat may be largely accounted for by efflux from hepatocytes into the general circulation, the quantitation of plasma GSH turnover in vivo could provide a noninvasive index of hepatic glutathione metabolism. We developed a method to estimate plasma glutathione turnover and clearance in the intact, anesthetized rat using a 30-min unprimed, continuous infusion of 35S-labelled GSH. A steady state of free plasma glutathione specific radioactivity was achieved within 10 min, as determined by high-pressure liquid chromatography with fluorometric detection after precolumn derivatization of the plasma samples with monobromobimane. The method was tested after two treatments known to alter hepatic GSH metabolism: 90 min after intraperitoneal injection of 4 mmol/kg buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, and after a 48-h fast. Liver glutathione concentration (mean ± SEM) was 5.00 ± 0.53 μmol/g wet weight in control rats. It decreased to 3.10 ± 0.35 μmol/g wet weight after BSO injection and to 3.36 ± 0.14 μmol/g wet weight after fasting (both p < 0.05). Plasma glutathione turnover was 63.0 ± 7.46 nmol∙min−1∙100 g−1 body weight in control rats, 35.0 ± 2.92 nmol∙min−1∙g−1 body weight in BSO-treated rats, and 41.7 ± 2.28 nmol∙min−1∙g−1 body weight after fasting (both p < 0.05), thus reflecting the hepatic alterations. This approach might prove useful in the noninvasive assessment of liver glutathione status.Key words: glutathione, nutrition, starvation.
Publisher
Canadian Science Publishing
Subject
Physiology (medical),Pharmacology,General Medicine,Physiology
Cited by
21 articles.
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