Glutathione transferase, hepatic

P. H., Cytochrome P 450 isoenzymes, epoxide hydrolase and glutathione transferases in rat and human hepatic and extrahepatic tissues, J. Pharmacol. Exp. Ther. 1990, 253, 387-394. 

Schramm H, Robertson LW, Oesch F. 1985. Differential regulation of hepatic glutathione transferase and glutathione peroxidase activities in the rat. Biochem Pharmacol 34(20) 3735-3739. 

Bolton RM, Ahokas JT. 1997. Purification and characterization of hepatic glutathione transferases from an insectivorous marsupial, the brown antechinus (Antechinus stuartii). Xenobiotica 27 573-586. 

Table VII. Hepatic Epoxide Hydrase and Glutathione Transferase in Normal and Ascorbate Deficient Guinea Pigs...

Induction of Hepatic CYPl A Oxygenases and Phase II Enzymes. PCBs induce hepatic Phase I enzymes (CYP oxygenases) and Phase II enzymes (e.g., UDP glucuronyltransferases, epoxide hydrolase, or glutathione transferase) to varying degrees and specificities (Connor et al. 1995 Hansen 1998 Safe... 

Ibufenac reduces hepatic clearance of both indocyanine green and bilirubin (H5). This drug also inhibits glucuronyl transferase (H5) and S-aryl glutathione transferase (B38). In vivo, phenylbutazone depresses bilirubin excretion, but not that of BSP in vitro, the enzymes conjugating bilirubin and BSP, respectively, are both inhibited. There is no effect on the clearance of indocyanine green (H5). 

Metabolic activation. Although the kidney does not contain as much cytochromes P-450 as the liver, there is sufficient activity to be responsible for metabolic activation, and other oxidative enzymes such as those of the prostaglandin synthetase system are also present. Such metabolic activation may underlie the renal toxicity of chloroform and paracetamol (see below Chapter 7). Other enzymes such as C-S lyase and glutathione transferase may also be involved in the activation of compounds such as hexachlorobutadiene (see Chapter 7). In some cases hepatic metabolism may be involved followed by transport to the kidney and subsequent toxicity. 

Seidegard, J., Guthenberg, C., Pero, R. W., and Mannervik, B., The trans-stilbene oxide-active glutathione transferase in human mononuclear leucocytes is identical with the hepatic glutathione transferase mu. Biochem. J. 246, 783-785 (1987). 

DATS which are potent inhibitors of BP-induced fore-stomach cancer in mice, resulted in a significant increase, as compared with control, in bodi hepatic (3.0-, 3.2-and 4.4-fold, respectively) and fore-stomach (1.5-, 2.7-and 2.7-fold, respectively) glutathione transferase (GST) activity toward anti-7P,8a-dihy oxy-9a, 1 Oa-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (anti-BPDE), which is the ultimate carcinogen of BP [102, 107]. On the contrary, this activity was not increased in either organ by dipropyl sulfide (DPS), which is ineffective against BP-induced fore-stomach cancer. The pulmonary GST activity was not increased by any of the tested OSCs. Even though epoxide hydrolase (EH) activity was differentially altered by these OSCs, a correlation between chemopreventive efficacy of OSCs and their effects on EH activity was not apparent [102]. The chemopreventive efficacy of these OSCs correlated with their ability to increase the expression of GST n. For example, DAS treatment resulted in approximate increases of 1.7- and 2.2-fold in hepatic and fore-stomach GST n expression, respectively, over the control. Treatment of mice with DATS, which is a relatively more potent inhibitor of BP-induced fore-stomach cancer than DAS, resulted in about 3.8- and 3,2-fold increases, respectively, in hepatic and fore-stomach GST n expression over the control. On the contrary, the expression of hepatic and fore-stomach GST n was increased only marginally (10-20%) upon DPS administration [107],... 

Ito, Y Maeda, S. Souno, K. Ueda, N. Sugiyama, X. Induction of hepatic glutathione transferase and suppression of 7,12-dimethylbenz[a]anthracene-induced chromosome aberrations in rat bone marrow cells by Sudan III and related azo dyes. J. Natl. Cancer Inst. 1984, 73, 177-183. 

MARCH T H, JEFFERY E H and WALLIG M A (1998) The crucifetous nitrile, cramhene, induces rat hepatic and pancreatic glutathione S-transferases , Toxicol Sci, 42 82-90. 

Iscan, M., B.C. Eke, and T. Coban. 1993. Combined effects of cadmium and nickel on hepatic glutathione 5-transferases in rats. Comp. Biochem. Physiol. 104C 453-456. 

Kirby, G.M., J.R. Bend, I.R. Smith, and M.A. Hayes. 1990. The role of glutathione s-transferases in the hepatic metabolism of benzo[a]pyrene in white suckers (Catostomus commersoni) from polluted and reference sites in the Great Lakes. Comp. Biochem. Physiol. 95C 25-30. 

Foureman GL, Hernandez O, Bhatia A, et al. The stereoselectivity of four hepatic glutathione S-transferases purified from a marine elasmobranch (Raja erinacea) with several K-region polycyclic arene oxide substrates. Biochim Biophys Acta 1987 914(2) 127-135. 

Das M, Agarwal AK, Seth PK. 1982. Regulation of brain and hepatic glutathione-S-transferase by sex hormones in rats. Biochem Pharmacol 31(23) 3927-3930. 

Two studies were located in which rats received di- -octylphthalate dietary exposures of 250 or 500 mg/kg/day for either 10 or 26 weeks (Carter et al. 1992 DeAngelo et al. 1986). Five male rats were first initiated with a single subcarcinogenic intraperitoneal dose of diethylnitrosamine (30 mg/kg), followed by partial hepatectomy. Di-w-octylphthalatc caused substantial increases in gamma-glutamyltranspeptidase (GGT) positive liver foci when compared with the controls (e.g., from 3.5 to 20.8 foci/cm2) or in hepatic levels of marker enzymes for altered cellular foci (GGT and glutathione 5-transferase [GST]). Only a slight increase (threefold) was observed for carnitine acetyltransferase (CAT) activity, a marker for peroxisome... 

---