IMPACT OF CEPHALORIDINE ON GLUTATHIONE AND RELATED ENZYMES - COMPARISONS OF IN-VIVO AND IN-VITRO RAT MODELS

Citation
F. Moritz et al., IMPACT OF CEPHALORIDINE ON GLUTATHIONE AND RELATED ENZYMES - COMPARISONS OF IN-VIVO AND IN-VITRO RAT MODELS, Archives of toxicology, 70(2), 1995, pp. 104-111
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Toxicology
Journal title
ISSN journal
0340-5761
Volume
70
Issue
2
Year of publication
1995
Pages
104 - 111
Database
ISI
SICI code
0340-5761(1995)70:2<104:IOCOGA>2.0.ZU;2-7
Abstract
The aim of this study was to investigate the early effects of cephalor idine (CPH) on glutathione-dependent phase II detoxification in the ra t proximal tubular cell and to find an in vitro alternative to the in vivo model. The in vivo study was conducted in three groups of rats wh ich received CPH at doses of 250, 500 or 750 mg/kg per day for 3 days, while another group received 500 mg/kg as a single dose. For the in v itro study, rat renal proximal tubular cultured cells were exposed to CPH at concentrations of 0.3, 0.6, 1, 1.7 mM for 24, 48 and 72 h. Glut athione-dependent detoxification was evaluated in vivo and in vitro on the basis of total intracellular glutathione (GSH), glutathione S-tra nsferase (GST) and glutathione peroxidase (GPX). Glutathione reductase (GRED) and GST mRNA levels were also determined. Results of in vivo a nd in vitro models were comparable in terms of the early increase of G SH, GST and GRED. This increase had a bell-shaped dose-response with a maximum at 500 mg/kg in vivo and 1 mM in vitro. Beyond these doses, G SH and its dependent enzyme levels decreased, associated with cytotoxi city in vitro and renal insufficiency in vivo. The increased GST activ ity was associated with an increased level of GST7 in vivo and a marke dly increased level of GST1-2 in vitro. We concluded that the in vitro model can be used as an alternative to animal experimentation to stud y glutathione-dependent detoxication. Low cytotoxic doses of CPH induc ed an early increase of glutathione phase II-dependent detoxification enzymes.