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Modulation of rat liver and kidney GST activity and expression by oral administration of phenethyl isothiocyanate.

Violetta K. Krajka-Kuźniak ,  Hanna M. Szaefer ,  Wanda Baer-Dubowska 

Poznan University of Medical Sciences, Department of Pharmaceutical Biochemistry, ul. Swiecickiego 4, Poznań 60-781, Poland

Abstract

The glutathione S-transferases (GSTs) are superfamily of enzymes which catalyze the conjugation of some electrophilic compounds with glutathione. Based on the structural, physicochemical, enzymatic and immunological properties cytosolic GSTs are divided into four classes: alpha, mu, pi and theta. The constitutive expression and induction of these isoforms in liver and kidney may be responsible for tissue specific susceptibility to cytotoxins and carcinogens. Moreover modulation of GST activity and expression may be involved in the mechanism of chemopreventive action of cruciferous vegetables. Naturally occurring isothiocyanates are a constituents of cruciferous vegetables, including cabbage, cauliflower, brussels sprouts, radishes and watercress. Among a wide variety of isothiocyanates that are naturally occuring, phenethyl isothiocyante (PEITC) was the most effective chemopreventive agent known. PEITC is an effective inhibitor of lung tumorigenesis induced in rats and mice by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Moreover PEITC was reported to inhibit liver tumor by N-nitrosodiethylamine in mice and esophageal tumor by N-nitosobenzylmethylamine in rats.

Our previous studies demonstrated the modulation of isozymes GST by cabbage and sauerkraut juice in rat liver and kidney. In order to explain to what extent the effect of cabbage is related to phenethyl isothiocyanate, in this study the total activity of GST and expression of GSTs alpha, mu, pi and theta by Western blot in rats liver and kidney were analyzed. Male Wistar rats were treated by gavage with PEITC for 4, 10 and 30 days. The control rats received vehicle only (olive oil).

Administration of PEITC for 4 days significantly (by 61%) enhanced activity of GST in rat liver. The same effect was observed after 10 and 30 days of exposure. But in kidney the highest increase (24-32%) of the enzyme activity was observed when PITC was administered for 4 and 10 days. Western blot analysis showed that PEITC increased the expression of GST class alpha and mu (by 20-30%) in liver at all time points of exposure, but did not affect the GST theta in this tissue. The constitutive expression of GST pi was not detected in liver. Expression of renal GST alpha and mu were slighty elevated of PITC treated animals in comparison with non-treated control.

The results indicate that the increase the total activity and expression of GST isozymes by PEITC may play role in their biological activity and chemoprotective properties of cabbage.

 

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Related papers

Presentation: Poster at Zjazd Polskiego Towarzystwa Biochemicznego, Sympozjum G, by Violetta K. Krajka-Kuźniak
See On-line Journal of Zjazd Polskiego Towarzystwa Biochemicznego

Submitted: 2007-04-26 10:34
Revised:   2009-06-07 00:44