Quantification of individual glutathione Emphasis

Authors: Alyson E Mitchell Jeffrey Lakritz A Daniel Jones

Publish Date: 2000/06/17

Volume: 74, Issue: 4-5, Pages: 215-221

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Abstract

Acute exposure to naphthalene produces severe bronchiolar epithelial cell necrosis in mice whereas subchronic exposure to naphthalene 200 mg/kg/7 days fails to produce epithelial necrosis and renders the animals tolerant to subsequent challenge doses of naphthalene Mechanisms responsible for the development of tolerance have not been delineated The few studies exploring naphthalene tolerance focus on expression of microsomal enzymes and have yet to delve into expression of the hepatic detoxification enzymes such as glutathione Stransferases GSTs EC 25118 Glutathione conjugation catalyzed by GSTs accounts for one of the two primary routes of naphthalene detoxification In this study we rigorously quantify levels of individual GST isozymes expressed within the livers and lungs of mice with acquired tolerance to naphthalene Subchronic exposure to naphthalene increases the abundance of some hepatic GSTs to levels as much as 68 greater than controls Naphthalenetolerant mice displayed increases in mGSTM1 51 mGSTM2 58 and mGSTP1 66 whereas no significant difference in mGSTA3 was observed between exposed and control mice Extracts of pulmonary tissues from naphthalenetolerant mice showed minor increases in levels of mGSTP1 7 and Peak 8 isozyme 27 and decreases in levels of mGSTM1 31 mGSTM2 17 and mGSTA3 8 The total enzymatic activity for the conjugation of 1chloro24dinitrobenzene CDNB was 22 lower in lung extracts from naphthalenetolerant animals than in controls These results indicate that induction of hepatic GSTs is substantial and may be an important factor in the development of tolerance to naphthalene

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