Intestinal Glutathione S-transferase Activities Research Articles

The effect of dietary supplementation with the citrus limonoids, limonin and nomilin on xenobiotic-metabolizing enzymes in the liver and small intestine of the rat

The aim of this study was to assess the effect of the citrus compounds, limonin and nomilin on activities of the phase I cytochrome P450 enzyme system and the phase II enzyme glutathione S-transferase (GST) in the liver and small intestine of the rat. Male Wistar rats were fed an American Institute of Nutrition-76 (AIN-76) diet containing increasing doses of limonin or nomilin (1, 2, 5 and 10 mg/day) for 10 days. A control group received the AIN-76 diet alone. The positive control group was fed the control diet containing 3-methylcholanthrene (3-MC; 15mg/day), a known inducer of cytochrome P450 and GST. No significant ( P < 0.05) changes were observed in liver and small intestine cytochrome P450 isoenzyme activities from animals fed diets containing limonin or nomilin. In contrast, GST activity increased in a dose-dependent manner in the liver of rats fed diets containing limonin and nomilin. A significant dose-dependent increase in small intestinal GST activity was also observed in nomilin fed animals. Our results add to the increasing body of evidence that these citrus limonoids are inducers of the detoxifying enzyme GST.

Effects of age and strain on small intestinal and hepatic antioxidant defense enzymes in Wistar and Fisher 344 rats

Age- and strain-associated alterations in intestinal and hepatic antioxidant defense enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione- S-transferase (GST), and lipid peroxidation were examined in Wistar and F344 rats of both strains aged 2 weeks, 2.5, 10 and 23 months. In the small intestine, activities of SOD and GSH-PX and lipid peroxidation were not affected by age or strain difference. Intestinal GST activity was noticeably increased with age in both strains, but somewhat different pattern of age-related changes occurred between two strains. Wistar rats aged 23 months had a significantly higher intestinal GST activity than corresponding age of F344 rats. In the liver, cytosolic SOD activity was not affected by age and strain, whereas GSH-PX and GST activities and lipid peroxidation were markedly influenced by age or strain difference. In particular, hepatic GSH-PX in Wistar rats resulted in a significant increase after 10 months of age and stayed at this level till 23 months of age we examined. Also, Wistar rats showed a higher lipid peroxidation in the liver of 2.5 months old when compared with corresponding age of F344 rats. However, F344 rats did not show any significant age-dependent changes in GSH-PX and lipid peroxidation. In contrast, the GST activity did show much of an age-associated alteration in both strains. Age-associated change in GST activity of Wistar rats was much greater than that observed in F344 rats, especially late in the lifetime (23 months old). It is concluded from our results that age has profound impact on development of some antioxidant enzymes in the small intestine and liver and also strain-related difference in development of antioxidant defense system was observed at least some time of rat life.

Age-related changes in antioxidant enzyme activities in the small intestine and liver from Wistar rats.

The present study was designed to determine age-related changes in intestinal and hepatic antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione-S-transferase (GST), and lipid peroxidation in male Wistar rats (n = 8) aged 2 wk, 2.5 mon, 5 mon, 10 mon, and 23 mon. In the small intestine, cytosolic SOD, GSH-PX activities and lipid peroxidation were not affected by age, but intestinal GST activity was noticeably enhanced as age increased. In particular, intestinal GST activity in 23 mon old rats was 3 times as strong as that in 2 wk old rats. In the liver, the activity of hepatic cytosolic SOD was not affected by age, whereas GSH-PX and GST activities in rats aged 10 mon and 23 mon were much stronger than those in rats aged 2 wk, 2.5 mon, and 5 mon. The increased lipid peroxidation in 2.5 mon and 5 mon old rats was observed when compared with that of other groups. It is therefore concluded from the results presented here that age greatly increases GST activity in the small intestinal mucosae and increasing GSH-PX, GST activities and lipid peroxidation in the liver from male Wistar rats.

Modulation of Glutathione S-Transferase Activity and Isozyme Pattern in Liver and Small Intestine of Rats Fed Goitrin- and T 3-Supplemented Diets

Goitrin is a potent goitrogen that has been shown to induce glutathione S-transferase (GST) activity and to increase aflatoxin detoxification. In the present study with rats, dietary goitrin (200 mg/kg diet) produced a hypothyroid state and significantly increased levels of hepatic GSSG (l.4-fold), GST protein (1.4-fold) and GST activity against chlorodinitrobenzene (CDNB) (1.7-fold). Cotreatment with dietary triiodothyronine (T3) reversed these effects in a dose-related manner. Intestinal GST activities against CDNB and epoxynitrophenoxypropane did not change with goitrin or T 3 treatment. HPLC analyses showed that, in the liver, goitrin treatment increased the levels of GST-Ib and -7 by 3.5- and 5-fold, respectively, and decreased the level of GST-3 by 50%. Cotreatment with T 3 returned levels of GST-7 and -3 to control levels but only partially reduced the level of GST-1b. In the small intestine, goitrin increased the level of GST-1b by 28% and decreased the level of GST-7 by 34% compared with those of controls; thyroid hormone treatment produced no additional effect on GST in this organ. Selenium deficiency altered thyroid hormone status but significantly affected the level only of hepatic GST-3, which was reduced by 30% compared with that of controls. These results indicate that a modified thyroid hormonal status plays an important role in the GST-inducing effects of goitrin. A possible mechanism of thyroid-dependent GST induction by goitrin is discussed.

Enhancement of Cytosolic and Microsomal Glutathione S‐Transferase Activities in Liver and Small Intestine from Female Rats During Lactation

The influence of lactation on hepatic and intestinal glutathione S-transferase activities in mother rats was studied. Cytosolic and microsomal activities were assessed 7, 14 and 21 days after delivery, using 1-chloro-2,4-dinitrobenzene as substrate. Cytosolic and microsomal activities from liver and small intestine determined 7 days post partum did not differ from those of virgin female rats. The hepatic cytosolic activity was significantly increased with respect to that of virgin females 14 days after delivery and tended to revert to the control value on day 21 of lactation, whereas the intestinal activity was increased on day 14 and remained augmented even 21 days post partum. Although the respective microsomal activities showed percent increases higher than those of the cytosolic enzymes, they both exhibited a similar pattern of stimulation in response to lactation.

Intestinal glutathione S-transferase activity (GST): GABA inhibition of liver regeneration

Intestinal glutathione S-transferase activity (GST): GABA inhibition of liver regeneration

Effect of diet and route of administration on the DNA binding of aflatoxin B1 in the rat.

The effects of dietary Brussels sprouts and indole-3-carbinol (I3C) on xenobiotic-metabolizing enzyme activities and hepatic aflatoxin B1 (AFB1)-DNA binding were determined in rats. Animals were dosed intraperitoneally (i.p.) or intragastrically (i.g.) with [3H]AFB1 and killed 2 (i.p.) or 3 (i.g.) h later. Brussels sprouts caused a significant (P less than 0.01) 50-60% decrease in hepatic AFB1-DNA binding, and increased hepatic and intestinal glutathione S-transferase (GST) activities. Hepatic mono-oxygenase (AHH and ECD) activities were not altered in sprouts-fed rats, but greater than 2-fold increases in intestinal AHH and ECD activities were found. Although I3C increased intestinal AHH and ECD activities similarly to Brussels sprouts, I3C did not significantly decrease AFB1 binding, nor did it increase hepatic or intestinal GST activity. Route of administration did not alter the percentage inhibition of binding in comparison to control rats in either treatment group, suggesting that the small intestine may not play a significant role in the metabolism of AFB1. In a second experiment, rats were dosed either i.p. or i.g. with [3H]AFB1 and killed 2, 6, 12, 24 or 48 h later. Hepatic AFB1-DNA binding and tissue radioactivity levels were determined. Brussels sprouts once again significantly (P less than 0.001) decreased hepatic AFB1-DNA binding. Route of administration of the carcinogen did not affect DNA binding over time in sprouts-fed animals, confirming our previous results.

Intestinal glutathione S-transferase activity in flounder Platichthys flesus collected from contaminated and reference sites

Intestinal glutathione S-transferase activities were measured during the GEEP Workshop in flounder Platichthys flesus collected from Langesundfjord, Norway. Though enzyme activities were generally higher in fish collected from 3 polluted sites by comparison with a reference site, the only significant differences in activities between the 3 sites ran counter to the anticipated pollution gradient. The results suggest that intestinal glutathione S-transferase activity may not be a sensitive indicator of pollution exposure under field conditions.

The effects of dietary cabbage on xenobiotic-metabolizing enzymes and the binding of aflatoxin B 1 to hepatic DNA in rats

The effect of dietary cabbage ( Brassica oleracea) on the binding of aflatoxin B 1 (AFB 1) to hepatic DNA and on the activities of liver and intestinal microsomal and cytosolic enzymes was studied in weanling male Fischer 344 rats. Freeze-dried cabbage was fed to rats at a level of 25% in the diet for 21 days, while others received a basal diet. In the cabbage-fed group there was an 87% ( P < 0.01) reduction in the binding of AFB 1 to hepatic DNA 2 hr after the ip injection of [ 3H]AFB 1 (3 μg/kg). There was also a 41% ( P < 0.05) increase in liver weight expressed relative to body weight. Hepatic and intestinal glutathione S-transferase activities were significantly increased (2.1- and 2.3-fold, respectively) over those in rats fed the basal diet. Hepatic and intestinal microsomal epoxide hydrolase activities were significantly increased (2.6- and 1.4-fold, respectively) over the basal group. Intestinal aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin O-deethylase (ECD) activities were significantly increased (2.3- and 2.5-fold, respectively), over the basal group but dietary cabbage had no significant effect on hepatic AHH or ECD activities.