Relative activities of organosulfur compounds derived from onions and garlic in increasing tissue activities of quinone reductase and glutathione transferase in rat tissues

There is evidence that onions and garlic protect against cancer in humans. It has been suggested that this effect is due to the organosulfur compounds in these vegetables and that these substances act through induction of phase II detoxification enzymes. In the present studies, we have compared the ability of diallyl sulfide, dially disulfide, and diallyl trisulfide, compounds that are derived from garlic, to increase the activity of the phase II enzymes quinone reductase and glutathione transferase in a variety of rat tissues. We have also examined the onion-derived substances, dipropyl sulfide, dipropyl disulfide, dipropenyl sulfide, and dipropenyl disulfide, under identical conditions. Diallyl trisulfide and diallyl disulfide were potent inducers of the phase II enzymes. Dipropenyl disulfide was much less active, while little effect on enzyme activity was seen in animals dosed with dipropyl disulfide. Diallyl sulfide and dipropyl sulfide were weak inducers of quinone reductase and glutathione transferase, but dipropenyl sulfide was very active, with an effect similar to that of diallyl disulfide. It is possible that diallyl disulfide and diallyl trisulfide are important in the anticancer action of garlic, while dipropenyl sulfide could be involved in the beneficial action of onions.     

Changes in Cu,Zn-superoxide dismutase, cytochrome c oxidase, glutathione peroxidase and glutathione transferase activities in copper-deficient mice and rats.

Dietary copper deficiency was produced in Swiss albino mice and Sprague Dawley rats to compare changes in selected antioxidant enzymes. A 5-wk dietary treatment was employed, starting approximately 1 wk after birth for mice (initially via dams) and 3 wk after birth for rats. An additional confirmatory experiment was conducted with mice using the postweanling paradigm. Mouse offspring (6 wk of age) and rats (8 wk of age) maintained on a Cu-deficient treatment were compared with Cu-adequate controls. Compared with Cu-adequate animals, Cu-deficient mice and rats were anemic, had lower ceruloplasmin activities and liver copper levels, and had higher relative weights of heart and small intestine. Activity of cytochrome c oxidase (mice) and Cu,Zn-superoxide dismutase (mice and rats) was lower in all seven organs examined from Cu-deficient animals compared with Cu-adequate animals, although there were organ and species differences. Compared with Cu-adequate controls, glutathione peroxidase activity was lower in liver and plasma of Cu-deficient mice and rats. Hepatic glutathione transferase activity was markedly lower in those Cu-deficient mice started on treatment at 1 wk of age but not in those mice or rats subjected to postweanling copper deficiency.     

Influence of dietary peroxides, selenium and vitamin E on glutathione peroxidase of the gastrointestinal tract.

The influence of dietary peroxides, vitamin E and selenium on glutathione peroxidase (GSH-Px) activity in the gastrointestinal tract of the rat was investigated. Feeding 7% oxidized stripped corn oid (peroxide value 1,000) in a diet adequate in selenium and vitamin E increased the specific activity of GSH-Px in the stomach mucosa. Feeding oxidized oil produced an increase in the wet weight of the intestinal mucosa which was associated with a decrease in the specific activity of the enzyme. Total GSH-Px activity in the intestinal mucosa was unchanged or moderately increased. These changes were unaffected by the presence of vitamin E in the diet. Dietary peroxides had no effect on GSH-Px activity in the plasma or in the perirenal and paraepididymal adipose tissues. Subacute vitamin E deficiency had no consistent effect on the activity of the enzyme in several tissues examined. In rats fed a Se deficient diet glutathione peroxidase activity decreased markedly in most tissues but only slightly in the intestinal mucosa. The moderate decrease in the intestine may be explained by the accessibility of residual dietary Se to the mucosal cells. The role of Se in the detoxification of peroxides in foods and the response of gastrointestinal GSH-Px to dietary peroxides are discussed.     

Chlorophyll derived from Chlorella inhibits dioxin absorption from the gastrointestinal tract and accelerates dioxin excretion in rats

We investigated the effects of chlorophyll derived from Chlorella on gastrointestinal absorption of seven types of polychlorinated dibenzo-p-dioxin (PCDD) and 10 types of polychlorinated dibenzofuran (PCDF) in Wistar rats. Twenty-eight rats were randomly distributed into seven groups (n = 4). After overnight food deprivation, rats were given 4 g of the basal diet or 4 g of the chlorophyll diet containing 0.01-0.5% chlorophyll one time on day 1; each diet also contained 0.2 mL PCDD and PCDF standard solutions. The amounts of fecal excretion of PCDD and PCDF congeners from days 1 to 5 in the group fed 0.01% chlorophyll were 64.8% for 1,2,3,7,8-pentaCDD, 78.6% for 1,2,3,4,7,8-hexaCDD, 73.5% for 1,2,3,6,7,8-hexaCDD, 58.5% for 1,2,3,7,8,9-hexaCDD, 33.3% for 1,2,3,4,6,7,8-heptaCDD, 85.7% for 1,2,3,7,8-pentaCDF, 77.3% for 2,3,4,7,8-pentaCDF, 88.6% for 1,2,3,4,7,8-hexaCDF, 78.0% for 1,2,3,6,7,8-hexaCDF, 62.5% for 1,2,3,7,8,9-hexaCDF, 84.1% for 2,3,4,6,7,8-hexaCDF, 41.7% for 1,2,3,4,6,7,8-heptaCDF, and 40.0% for 1,2,3,4,6,7,8-heptaCDF greater (p < 0.01) than those of the control group, respectively. The fecal excretion of PCDD and PCDF congeners was remarkably increased along with the increasing dietary chlorophyll. The amounts of PCDD and PCDF congeners in rats on day 5 administered dioxin mixtures were lower in the 0.01% chlorophyll group than in the control group, ranging from 3.5 to 50.0% for PCDD congeners and from 3.7 to 41.7% lower for PCDF congeners, except for 2,3,7,8-tetrachlorodibenzofuran. The amount of PCDD and PCDF congeners in rats was remarkably decreased along with the increasing dietary chlorophyll. These findings suggest that chlorophyll is effective for preventing dioxin absorption via foods.     

The effect of cholesterol feeding on lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in the liver of rats

Liver cholesterol, phospholipid, triglyceride, lipid peroxide and glutathione levels as well as glutathione peroxidase and glutathione transferase activities were determined in rats fed a high-cholesterol (2%, w/w), high-cholic acid (0.5%, w/w) diet for 3 months. Cholesterol feeding caused an increase in hepatic cholesterol and triglyceride levels, but no change was observed in hepatic phospholipid levels. In addition, a significant increase in hepatic lipid peroxide levels and a significant decrease in glutathione peroxidase and glutathione transferase activities have been observed. However, hepatic glutathione content after cholesterol feeding remained unchanged. These results show that cholesterol feeding leads to the stimulation of hepatic lipid peroxidation as well as impairment of glutathione-related enzyme activities in rats.     

The dose-dependent effects of ingested chrysotile on DNA synthesis in the gastrointestinal tract, liver, and pancreas of the rat.

The effects of single oral administration of saline suspensions of chrysotile A to fasting male albino rats on DNA synthesis in the GI tract, pancreas, and liver were studied after a subsequent interval of 3 days. Incorporation of [³H]TdR was elevated in the whole stomach, duodenum, and jejunum following administration of chrysotile in the dose range of 5 to 100 mg/kg; incorporation in the liver was, however, reduced. There was no change in pancreatic and colonic [³H]TdR uptakes following administration of chrysotile. Preliminary data suggest that physicochemical alterations of chrysotile by gastric acid may influence its subsequent effects on DNA synthesis.     

Influence of zinc deficiency on retinal reductase and oxidase activities in rat liver and testes.

The influence of zinc deficiency on vitamin A metabolism in rats was investigated by assessing two specific enzymes involved in its metabolism viz retinal reductase and retinal oxidase in the liver as well as in the testes. The activity of retinal reductase in the liver was not altered in zinc deficiency. Retinal oxidase activity on the other hand, was increased approximately 1.5 fold over the pair-fed controls. In contrast, both retinal reductase and oxidase in the testes were decreased during zinc deficiency. The effects of zinic deficiency on vitamin A metabolism in the liver could be partly attributed to the secondary effect of reduced food intake and growth. However, the effects seen in the testes on the metabolic enzymes of vitamin A appear to be due to zinc deficiency per se. The liver concentration of vitamin A (microgram/g) as well as total vitamin A (microgram/liver) were higher in the zinc-deficient rats when compared to the zinc-sufficient rats although not significantly different from the pair-fed controls. In aggreement with previous reports, the plasma vitamin A in zinc-deficient rats were found to be markedly lowered compared to zinc sufficient ad libitum controls.     

Roentgenographic study of ethosuximide-induced functional changes in rat gastrointestinal tract and their modulation by Nivalin in a chronic experiment.

Ethosuximide, a typical antiabsence drug, causes gastrointestinal complaints in the drug-treated patients. In the present study we investigated in an experimental model the functional disturbances occurring in rat gastrointestinal tract (GIT) after a 100-day chronic administration of ethosuximide. Contrast radiographic study of rat gastrointestinal tract was used. The mechanical activity of GIT smooth muscle (SM) preparations was measured using an in vitro isometric technique. The 100-day ethosuximide treatment induced atonia, disturbed peristalsis, and lead to a delay of the contrast material evacuation from the gastrointestinal tract combined with a reduction of the acetylcholine effect on the contractions of GIT smooth muscles in ethosuximide-treated rats. Nivalin cannot eliminate the ethosuximide-induced disturbances in the gastrointestinal tract after a 100-day administration of ethosuximide to the rats. It is thus assumed that Nivalin is not capable of compensating the inhibiting effect of ethosuximide. The authors assume that desensitization of acetylcholine receptors may occur and this reduces the effect of Nivalin action.     

Sulfation of the isoflavones genistein and daidzein in human and rat liver and gastrointestinal tract

Phytoestrogens, in particular the isoflavone aglycones genistein and daidzein, are thought to be the bioactive components of soy. Like estrogens, isoflavones can be sulfur-conjugated. However, although isoflavones in the serum are found largely in the form of glucuronide and sulfur conjugates following soy consumption, little is known regarding the relative contributions of sulfotransferases in the liver and small intestine to isoflavone sulfation. Since the sulfates may be deconjugated in target tissues, circulating isoflavone sulfates may act as a source of tissue aglycones. In the current study genistein and daidzein sulfotransferase activities were measured in cytosol from human and rat liver and gastrointestinal tract. Isoflavone sulfation in the human gastrointestinal (GI) tract was correlated with activities towards substrates for previously characterized human sulfotransferases. Western blots of human cytosols were also conducted using antisera towards human sulfotransferases SULT1E1 and SULT2A1. Whereas rat liver was almost fourfold more active than small intestine in sulfation of genistein, in the human, activities in the two tissues were comparable. In contrast, intestinal sulfation of daidzein was comparable to hepatic sulfation in the rat and significantly greater in the human. Genistein and daidzein sulfation occurred throughout the human GI tract, but with a different distribution and different interindividual variability. Whereas genistein sulfation in the human GI tract correlated significantly with sulfation of the prototypical human phenolic sulfotransferase SULT1A family substrate 2-naphthol (r2 = 0.71), daidzein sulfotransferase activity did not correlate with activities towards any prototypical sulfotransferase substrate or with genistein sulfation. Our results suggest that metabolism in the human GI tract has an important role in the generation of potentially bioactive isoflavone sulfates and a major role for the human phenolic sulfotransferase SULT1A family in metabolism of genistein in the gut. However, human intestinal daidzein sulfation appears to be catalyzed by a separate enzyme.     

Effect of guar gum, lignin and pectin on proteolytic enzyme levels in the gastrointestinal tract of the rat: a time-based study

The effects of dietary pectin (P), guar gum (G) and lignin (L) on stomach emptying and potential levels of pepsin, trypsin and chymotrypsin during a 2-h period after force-feeding were investigated in growing rats. All of the fibers delayed stomach emptying by 21-26 min. Total potential pepsin activity over 2 h decreased for P (57%), G (44%) and L (20%). In the intestine, total potential trypsin activity over 2 h increased for L (16%) but decreased for P (21%). Total potential chymotrypsin activity over 2 h increased for L (54%) and G (39%). Sixteen to 21% of the variability in intestinal activity over time was statistically attributable to variation in the weight of intestinal contents. The results indicate that fiber components altered proteolytic enzyme levels in the gastrointestinal tract, but the decreased protein utilization previously observed with these fibers is probably not due to reduced levels of intestinal proteases.     

Effect of dietary methionine on utilization of tissue selenium from dietary selenomethionine for glutathione peroxidase in the rat

To study the effect of dietary methionine on the bioavailability of Se from selenomethionine ([Se]Met), weanling rats were first loaded with Se by feeding 0.5 mg Se as [Se]Met per kg diet of a low methionine (0.17% by analysis) torula yeast-based diet for 21 d, and then were fed an Se-deficient diet (less than 0.02 mg Se/kg) supplemented with 0, 0.4 or 0.9% methionine for 28 d. Plasma, liver and muscle Se increased 2.6-, 2.5- and 2.2-fold, respectively, during [Se]Met supplementation, and then the tissue Se declined exponentially during the Se-deficient diet period. Plasma, liver and muscle glutathione peroxidase (GSH-Px) activities decreased 43-50% during the [Se]Met supplementation period in spite of the increase in tissue Se. When these [Se]Met-loaded rats were fed the Se-deficient diet and supplemented with methionine, tissue GSH-Px activities increased significantly within 3 to 7 d, but then decreased for the remainder of the experiment. Calculation of the percentage of tissue Se present as Se in GSH-Px indicated that substantial Se from dietary [Se]Met was stored in tissues in a form different from GSH-Px when a low methionine diet was fed. These results indicate that the dietary methionine level can modulate the availability of Se from dietary [Se]Met and from stored tissue [Se]Met; the inability of stored [Se]Met to provide Se for GSH-Px synthesis over a prolonged period of time suggests that [Se]Met may not be an optimum form for Se supplementation.     

Sulfated polysaccharides derived from dietary seaweeds increase the esterase activity of a lymphocyte tryptase, granzyme A

Intake of sulfated polysaccharides, such as fucoidan or lambda-carrageenan extracted from seaweeds, has been shown to enhance immune responses, resulting in inhibition of tumor growth. However, little is known about the mechanisms by which these sulfated compounds mediate the enhancement. In the present study, we examined the effect of sulfated polysaccharides from seaweeds on esterase activity of a lymphocyte tryptase, granzyme A (GzmA), which is believed to induce the production of cytokines in a variety of cells. Inclusion of fucoidan (from Fucus vesiculosus) or lambda-carrageenan (from Gigartina aciculaire and Gigartina) in the reaction mixture increased the hydrolysis of Nalpha-benzyloxy-L-lysine thiobenzyl ester (BLT) by a recombinant rat GzmA in a concentration-dependent manner. Heparin, a sulfated polysaccharide from animal tissues, also increase the BLT hydrolysis, but the effect was less remarkable than those of the polysaccharides from the seaweeds. Hanes-Woolf analysis revealed that the enhancements in the presence of these sulfated compounds from the seaweeds were attributed to the increases in the affinity of the enzyme toward the substrate but not to those in the turnover rate. Chondroitin sulfate A, a sulfated polysaccharide found in animal and plant tissues, showed no positive effect on the hydrolysis. In the present paper, we propose that the enhancement of immune responses by intake of the sulfated polysaccharides from seaweeds can be partially accounted for by their direct effects on GzmA.     

不同硒水平饲料对大鼠肝脏谷胱甘肽过氧化物酶和脱碘酶活性的影响

为了解不同饲料硒水平对大鼠肝脏中谷胱甘肽过氧化物酶和脱碘酶活性的影响及确定它们发挥最佳活性时的最低饲料硒水平。５４只体重为５０～６０ｇ的雄性断孔Ｗｉｓｔａｒ大鼠分成９组，分别喂以９种含硒水平为０．０１，０．０２，０．０３，０．０４，０．０５，０．０６，０．１，０．２和５ｍｇ／ｋｇ的不同饲料。实验持续２０周。９组动物２０周的体重增长除５ｍｇ／ｋｇ饲料组与０．１、０．２ｍｇ／ｋｇ饲料组之间有差异外，其余均没有显著性差异。谷胱甘肽过氧化物酶的活性随着饲料硒水平的升高而升高，当饲料硒含量为０．１，０．２和５ｍｇ／ｋｇ饲料时，活性达到最高。因此它发挥正常活性范围的最低饲料硒需要量为０．１ｍｇ／ｋｇ。９个组脱碘酶的活性（ｎｍｏｌ／ｍｉｎ．ｇ）在０．０５至０．２ｍｇ／ｋｇ饲料时活性最高，在５ｍｇ／ｋｇ饲料时酶活性降低，发挥最佳活性最低饲料硒需要量为０．０５ｍｇ／ｋｇ。