Microsomal Glutathione S-transferase Activity Research Articles

Effect of ethanol on the microsomal glutathione S-transferase activity in glutathione-depleted rat liver

Depletion of hepatic glutathione in male rats by starvation caused a significant increase in microsomal glutathione S-transferase activity, which was not affected by acute ethanol pretreatment. An additional depletion in fasted rats by diethylmaleate (0.5 g/kg) caused a further increase in the enzyme activity, but this increase was delayed in ethanol intoxicated rats. Although ethanol caused a small increase in hepatic microsomal lipid peroxidation in control animals, this effect of ethanol was not observed in diethylmaleate treated rats and thus was apparently not responsible for the delay in enzyme activation. It is suggested that the activation of microsomal glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene in glutathione-depleted rat liver may be produced by changes in thiol/disulfid ratio and/or some reactive oxygen species.

Effect of an acute dose of ethanol on lipid peroxidation and on the activity of microsomal glutathione S-transferase in rat liver.

Acute ethanol administration (1.5 g/kg) to fasted rats resulted in a small but significant increase in the content of conjugated dienes in the microsomal fraction of liver. Treatment with 4-methylpyrazole prior to ethanol ingestion was able to reduce the ethanol-induced lipid peroxide formation (measured as conjugated dienes). No depletion of glutathione occurred within the first 2 hrs following ethanol administration by which time lipid peroxide formation is well established. The ethanol-induced inhibition of N-ethylmaleimide-stimulated microsomal glutathione S-transferase activity correlates positively to the concentration of conjugated dienes in the microsomal fraction of liver.

Effect of phenobarbital on toxicity of pyrrolizidine (Senecio) alkaloids in sheep.

The effect of prolonged phenobarbital (PB) administration on the toxicity of Senecio jacobaea (SJ) was studied in sheep. Hepatic microsomal mixed function oxidase (MFO) activity was monitored. Pentobarbital sleeping times were decreased after 17 d of treatment, indicating initial induction of MFO. At 105 d of treatment, hepatic microsomal aminopyrine N-demethylase activity and cytochrome P-450 levels were increased (P less than .05) as a result of PB administration. No differences (P greater than .05) were observed in activity of microsomal epoxide hydrolase, glutathione S-transferase or liver glutathione as a result of SJ and (or) PB. Epoxide hydrolase activity in control sheep was about fivefold higher than values previously reported for rats. Liver Cu concentration was increased (P less than .05) in sheep receiving PB and SJ when compared with controls, but no differences (P greater than .05) were observed in the hepatic intracellular distribution of Cu as a result of PB and(or) SJ. Histopathological examination of liver revealed greater incidence and severity of lesions in animals receiving SJ, but PB did not appear to potentiate SJ intoxication. The results suggest that MFO induction by PB does not increase the susceptibility of sheep to SJ intoxication. Sheep possess a high activity of hepatic microsomal epoxide hydrolase which could account for their resistance to SJ intoxication.

Comparison of the distribution of microsomal and cytosolic glutathione S-transferase activities in different organs of the rat

Comparison of the distribution of microsomal and cytosolic glutathione S-transferase activities in different organs of the rat

Species variations in the sensitivity of the endoplasmic reticulum to the herbicide i.i.i. trifluoro-n-(2-methyl-4-phenyl sulfonyl phenyl) methane sulfonamide

1. The effects of the herbicide I.I.I. trifluoro- N-(2-methyl-4-phenyl sulfonyl phenyl) methane sulfonamide on the drug metabolising enzyme activities in livers of rat, mouse and guinea pig have been compared. 2. In all three animal models, the herbicide increased the activities of both aniline hydroxylase and p-aminopyrine demethylase. The greatest inductive effect was seen in the rat, while the least effect was evident in the guinea pig. 3. In mouse and guinea pig, 1.1.1. trifluoro- N-(2-methyl-4-phenyl sulfonyl phenyl) methane sulfonamide had no effect on the soluble or microsomal epoxide hydratases or the glutathione S-transferases. In the rat. however, the herbicide significantly decreased the microsomal epoxide hydratase activity, as well as the soluble and microsomal glutathione S-transferase activities. 4. These results are discussed in relation to factors responsible for species differences in the response to foreign compounds.

Studies of endogenous inhibitors of microsomal glutathione S-transferase.

Glutathione S-transferase is present in rat liver microsomal fraction, but its activity is low relative to the transferase activity present in the soluble fraction of the hepatocyte. We have found, however, that the activity of microsomal glutathione S-transferase is increased 5-fold after treatment with small unilamellar vesicles made from phosphatidylcholine. The increase in activity is due to the removal of an inhibitor of the enzyme from the microsomal membrane. The inhibitor is present in the organic layer of a washed Folch extract of the microsomal fraction. When this fraction of the microsomal extract is reconstituted in the form of small unilamellar vesicles, it inhibits microsomal glutathione S-transferase that had been activated by prior treatment with small unilamellar vesicles of pure phosphatidylcholine, but does not affect the activity of unactivated microsomal glutathione S-transferase. The inhibitor did not seem to be formed during the isolation of the microsomal fraction, and hence may be a physiological regulator of microsomal glutathione S-transferase. In this regard, both free fatty acid (palmitate) and lysophosphatidylcholine were shown to inhibit the enzyme reversibly. The results indicate that the activity of microsomal glutathione S-transferase is far greater than appreciated until now, and that this form of the enzyme may be an important factor in the hepatic metabolism of toxic electrophiles.

A comparison of induction of microsomal glutathione S-transferase activity in the liver of the mouse and rat by dietary 2(3)-tert-butyl-4-hydroxyanisole (BHA).

A comparison of induction of microsomal glutathione S-transferase activity in the liver of the mouse and rat by dietary 2(3)-tert-butyl-4-hydroxyanisole (BHA).

Differences in inducibility of particulate and cytosolic rat liver glutathione S-transferase activities.

1. Rat liver mitochondrial microsomal glutathione (GSH) S-transferase activities with 1-chloro-2,4-dinitrobenzene as substrate were 11.0 and 11.6%, and with 1,2-dichloro-4-nitrobenzene as substrate were 27.7 and 15.4%, of the corresponding cytosolic activities respectively. 2. Marked difference in inducibility of cytosolic and particulate GSH S-transferase activities were seen after pretreatment of animals with enzyme-inducing agents. 3-Methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin enhanced cytosolic GSH S-transferase activity only. Phenobarbital induced the cytosolic and microsomal enzymes only.

Effects of vitamin A deficiency on hepatic and extrahepatic mixed-function oxidase and epoxide-metabolizing enzymes in guinea pig and rabbit

Male guinea pigs and male rabbits were fed a vitamin A deficient diet for 9 weeks and for 12 weeks respectively. Hepatic levels of vitamin A were significantly reduced in the vitamin A deficient animals. The activities of some xenobiotic-metabolizing enzymes were measured in the liver, lung and small intestine. Aryl hydrocarbon hydroxylase, aniline hydroxylase, and 7-ethoxycoumarin deethylase activities were decreased in the vitamin A deficient guinea pig liver. However, in the guinea pig small intestine, aniline hydroxylase, 7-ethoxycoumarin deethylase, aminopyrine demethylase, and aryl hydrocarbon hydroxylase specific activities were increased. In rabbits, vitamin A deficiency decreased hepatic aniline hydroxylase and 7-ethoxycoumarin deethylase activities but increased intestinal aminopyrine demethylase activity. Enzyme activities in lung were not altered by vitamin A deficiency in guinea pig or rabbit. Microsomal epoxide hydrase and microsomal supernatant glutathione S-transferase activities in the three tissues of both species were not altered by vitamin A deficiency.

Biochemical effects of pure isomers of hexachlorobiphenyl—Hepatic microsomal epoxide hydrase and cytosolic glutathione S-transferase activities in the rat

Biochemical effects of pure isomers of hexachlorobiphenyl—Hepatic microsomal epoxide hydrase and cytosolic glutathione S-transferase activities in the rat

Activation of microsomal glutathione S-transferase activity by sulfhydryl reagents

Rat liver microsomes exhibit glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene as the second substrate. This activity can be stimulated 8-fold by treatment of the microsomes with N-ethylmaleimide and 4-fold with iodoacetamide. The corresponding glutathione S-transferase activity of the supernatant fraction is not affected by such treatment. These findings suggest that rat liver microsomes contain glutathione S-transferase distinct from those found in the cytoplasmic and that the microsomal transferase can be activated by modification of microsomal sulfhydryl group(s).