Effects of a dietary oxidized fat on cholesterol in plasma and lipoproteins and the susceptibility of low-density lipoproteins to lipid peroxidation in guinea pigs fed diets with different concentrations of vitamins E and C

To investigate the effect of a dietary oxidized fat on the concentrations of cholesterol in liver, plasma, and lipoproteins and the susceptibility of low-density lipoproteins (LDL) to lipid peroxidation, and to explore the effects of vitamins E and C, male guinea pigs were divided into five groups. Four groups were fed diets with an oxidized fat supplemented with 35 or 175 mg alpha-tocopherol equivalents/kg and 300 or 1000 mg of vitamin C/kg for 29 days. One group, used as a control, was fed the same basal diet with fresh fat with 35 mg alpha-tocopherol equivalents/kg and 300 mg of vitamin C/kg. Guinea pigs fed the oxidized-fat diets, irrespective of dietary vitamin E and C concentrations, had significantly lower concentrations of total cholesterol in the liver and a lower concentration of cholesterol in LDL than the control animals fed the fresh fat. According to the lag time before onset of lipid peroxidation, LDL of guinea pigs fed the oxidized-fat diet with 35 mg alpha-tocopherol equivalents and 300 mg vitamin C/kg were significantly more susceptible to copper-induced lipid peroxidation than those of guinea pigs fed the fresh fat diet. Within the groups fed the oxidized fat diets, increasing the dietary vitamin E concentration from 35 to 175 mg/kg significantly (p < 0.05) and increasing the dietary vitamin C concentration from 300 to 1000 mg/kg in tendency (p < 0.10) reduced the susceptibility of LDL to oxidation. LDL of guinea pigs fed the oxidized fat diets with 175 mg alpha-tocopherol equivalents/kg were even more resistant to oxidation than LDL of guinea pigs fed the fresh diet. In conclusion, the study shows that dietary oxidized fat influences the cholesterol metabolism and the susceptibility of LDL to lipid peroxidation; the latter can be modified by dietary vitamins E and C.     

Net vitamin C activity of erythorbic acid in guinea pigs

The enzyme activities, which are influenced by the vitamin C level in tissues, were measured to evaluate the vitamin C activity of erythorbic acid (ErA) in guinea pigs administered ErA. Guinea pigs were divided into two groups: animals in one group (control group) were administered 1, 5, and 100 mg/day ascorbic acid (AsA) and those in the other group (supplemented group) were administered 1, 5, 20, and 100 mg/day ErA for 16 days. At the end of the experimental period, they were sacrificed, blood was collected, and their livers were removed. The activities of liver aniline hydroxylase, of liver acid phosphatase, and of serum alkaline phosphatase, and the content of liver cytochrome P-450 were assayed. The activities of aniline hydroxylase and serum alkaline phosphatase and the content of liver cytochrome P-450 of the guinea pigs administered 1 mg ErA were lower than those of the guinea pigs administered 1 mg AsA. However, the enzyme activities and liver cytochrome P-450 content in the guinea pigs administered 5 mg or more of ErA were similar in level to those in the guinea pigs administered 5 mg AsA. These results suggested that administration of a considerably high amount of ErA to guinea pigs showed a similar vitamin C activity to that of AsA, which might suggest that vitamin C activity of ErA may be more than one-twentieth that of AsA, as has been generally believed.     

Effect of dietary ascorbic acid and vitamin E on metabolic changes in rats and guinea pigs exposed to PCB

The effect of the addition of dietary ascorbic acid and/or vitamin E (all-rac-alpha-tocopheryl acetate) in rats and guinea pigs exposed to PCB (polychlorinated biphenyls) was studied. Rats were fed diets containing one of three levels of vitamin E (30, 500 or 1000 mg/kg diet) with or without PCB (200 mg/kg diet). Guinea pigs were fed diets containing PCB (40 mg/kg diet) with 200 or 1000 mg ascorbic acid/kg diet and/or 70 or 2000 mg vitamin E/kg diet. For rats fed PCB, ascorbic acid in urine was 40-fold higher and in liver, 2-fold higher than for rats fed no PCB, and thiobarbituric acid-reactive substances (TBA-RS, indicators of lipid peroxidation) in liver was 1.5-fold higher. In rats fed PCB, high dietary vitamin E significantly lowered the urinary ascorbic acid and TBA-RS. Liver ascorbic acid was lowered by high dietary vitamin E only in control rats. In guinea pigs, feeding PCB caused severe growth retardation and the liver TBA-RS was 1.8-fold higher than in guinea pigs not fed PCB. Feeding high levels of both ascorbic acid and vitamin E was more effective in reversing the growth depression and in lowering TBA-RS level (due to PCB) than feeding the vitamins separately. Ascorbic acid metabolism in rats was affected by high dietary vitamin E. The possibility of a higher requirement for ascorbic acid and vitamin E in guinea pigs exposed to PCB was indicated. Interaction of ascorbic acid and vitamin E in animals exposed to PCB was suggested.     

Combined selenium and vitamin C deficiency causes cell death in guinea pig skeletal muscle

Combined antioxidant deficiencies of selenium and vitamin E or vitamin E and vitamin C in guinea pigs result in clinical illness. We hypothesized that combined selenium and vitamin C deficiency would have clinical consequences because in vitro interactions of these antioxidant nutrients have been reported. Because guinea pigs are dependent on dietary vitamin C, weanling male guinea pigs were fed selenium-deficient or control diet for 15 weeks before imposing vitamin C deficiency. Four dietary groups were formed and studied 3 weeks later: controls, vitamin C deficient, selenium deficient, and doubly deficient. Deficiencies were confirmed by determinations of glutathione peroxidase activity and vitamin C concentration in liver and skeletal muscle. Plasma creatine phosphokinase activity and liver, kidney, heart, and quadriceps histopathology were determined. Doubly deficient animals had moderately severe skeletal muscle cell death as judged by histopathology and plasma creatine phosphokinase activity of 6630 ± 4400 IU/L (control, 70 ± 5; vitamin C deficient, 95 ± 110; selenium deficient, 280 ± 250). Liver, kidney, and heart histology was normal in all groups. Muscle α-tocopherol levels were not depressed in the doubly deficient group, but muscle F₂ isoprostane concentrations were elevated in them and correlated with markers of cell death. We conclude that combining selenium and vitamin C deficiencies in the guinea pig causes cell death in skeletal muscle that is more severe than the injury caused by selenium deficiency. The elevation of muscle F₂ isoprostanes is compatible with the cell death being caused by oxidative stress.     

Effect of dietary vitamin E and selenium on DNA damage in fresh and frozen tissues

To determine whether deficiencies of dietary vitamin E and Se can elevate background DNA damage, rats were fed diets deficient in or supplemented with vitamin E (30 and 200 mg/kg diet) and Se (0.2 mg/kg diet) for 8 weeks. DNA damage was measured using the Comet (single-cell electrophoresis) assay and 8-oxodeoxyguanosine (8-oxo-dG) in liver, kidneys, and lymphocytes. We found that a deficiency of vitamin E and/or Se for 8 weeks did not significantly increase DNA damage in freshly isolated liver, kidneys, or lymphocytes. However, deficiency of vitamin E and/or Se for 8 weeks markedly increased DNA strand breaks in frozen kidney (-80 degrees C for 72 hours) and in lymphocytes incubated overnight at 37 degrees C, both of which were effectively prevented by supplementation of Se and vitamin E. However, vitamin E at 200 mg/kg did not afford more protection than it did at 30 mg/kg). Little or no significant increase in DNA damage was found in frozen livers. These results indicate that freezing or freeze-thawing of tissues may cause oxidative damage to DNA when the tissues are deficient in a major antioxidant, and that normal levels of vitamin E (30 mg/kg diet) and Se (0.2 mg/kg diet) are sufficient to prevent the damage. Thus, our results caution against the interpretation of DNA data obtained from frozen rat tissues or cells in animal studies with dietary vitamin E or Se deficiencies.     

Role of dietary vitamin E in cadmium-induced oxidative damage in rabbit's blood, liver and kidneys

The aim of this work was to determine the effect of dietary vitamin E intake on lipid peroxidation (LPO) by measuring thiobarbituric acid reactive substances (TBARS), vitamin E and reduced glutathione (GSH) levels, and glutathione peroxidase (GSH-Px: EC 1.11.1.9) activity in plasma, red blood cells (RBC), livers, and kidneys of rabbits dosed with cadmium (Cd). Six-month-old clinically healthy New Zealand White rabbits (8 in each group) were given tap water only, containing 1 g CdCl2/L, or tap water with CdCl2 plus vitamin E (100 mg dl-alpha-tocopheryl acetate in 0.2 mL corn oil) daily for 30 days. The vitamin E level in the plasma, liver, and kidneys was significantly higher in the control than in the Cd-only group, and TBARS levels were significantly lower. There were no statistical differences between the control and Cd-only groups GSH-Px activities and GSH levels in RBC, liver, and kidneys. Vitamin E levels in plasma, liver, and kidneys and GSH-Px activity in RBC were higher in the vitamin E group than in both control and Cd-only groups. However, the TBARS levels of RBC, liver, and kidneys in vitamin E administered group were decreased. Therefore, the present study demonstrates the effectiveness of vitamin E in reducing oxidative stress in Cd-treated rabbits and suggests that reductions in increased TBARS due to Cd toxicity may be an important factor in the action of vitamin E.     

软骨保护剂对Hartley豚鼠软骨组织和血清蛋白多糖的影响

目的观察软骨保护剂氨基葡萄糖(GS)和硫酸软骨素(CS)对原发性骨关节炎(OA)模型雌性Hartley豚鼠膝关节软骨组织结构、组织成分以及血清中蛋白多糖含量的影响。方法120只2月龄雌性Hartley豚鼠,随机分为三个试验组和一个空白对照组。三个试验组分别为:1g/kg bw GS组,0.5g/kg bw CS组,GS1g/kg bw+CS0.5g/kg bw联合使用组和蒸馏水对照组。自由饮水给予受试物,连续5个月。分别于给药前,给药1个月、2个月、3个月、4个月和5个月后,每组各取5只动物膝关节进行组织病理学(HE染色)和组织化学(PAS、Alcian Blue、和Mallory染色)检查以及血清蛋白多糖含量的检测。结果病理及组化检查:对照组在实验开始1个月后软骨组织病理积分即不断增高;GS组在给药三个月后才开始上升;CS组在给药的5个月中病理积分增高缓慢,仅第4个月上升较明显;联合使用组在给药的5个月中病理积分一直没有增高,并且给药5个月后的病理积分显著低于同组给药前期的积分。血清蛋白多糖含量:给药4个月后,GS组,CS组和联合使用组血清中蛋白多糖含量下降减少,与各自同期对照组相比差异均有显著性(P<0.05)。结论氨基葡萄糖和硫酸软骨素对豚鼠原发性软骨组织退化的发生、发展,以及血清蛋白多糖含量的下降均有延缓及抑制作用。并且以两者的联合作用最强,显现出一定的修复作用。     

Supplementation of vitamins C and E increases the vitamin E status but does not prevent the formation of oxysterols in the liver of guinea pigs fed an oxidised fat

Summary Background Dietary oxidised fats are a source of oxidative stress. They cause deleterious effects in animal organism by lowering the antioxidant status of tissues and enhancement of the formation of lipid oxidation products. The vitamins E and C might be useful to prevent the formation of oxidation products by dietary oxidised fats. Aim of the study The purpose of this study was to investigate whether or not supplementation of diets with vitamins E and C is able to prevent oxidative stress and the formation of lipid oxidation products caused by dietary oxidised fats. Among lipid oxidation products, oxysterols should be particularly considered because of their high pathophysiological effects. Methods Male guinea pigs were divided into five groups. Four groups were fed diets with an oxidised fat supplemented with 35 or 175 mg -tocopherol equivalents/kg and 300 or 1000 mg of vitamin C/kg for 29 days. One group, used as a control, was fed the same basal diet with fresh fat with 35 mg -tocopherol equivalents/kg and 300 mg of vitamin C/kg. Results The guinea pigs fed the oxidised fat diet with 35 mg -tocopherol equivalents/kg and 300 mg vitamin C/kg had significantly lower concentrations of tocopherols in various tissues, higher concentrations of various oxysterols and thiobarbituric acid-reactive substances in the liver, higher concentrations of glutathione in the liver and lower concentrations of glutathione in erythrocytes than the control animals fed the fresh fat. Increasing the dietary vitamin E concentration from 35 to 175 mg -tocopherol equivalents/kg and/or the dietary vitamin C concentration from 300 to 1000 mg/kg increased tissue tocopherol concentrations in guinea pigs fed the oxidised fat but did not influence concentrations of oxidation products in the liver and glutathione concentrations in liver and erythrocytes. Conclusion The results demonstrated that supplementation of vitamins E and C improves the vitamin E status but does not prevent the formation of lipid oxidation products in the liver of guinea pigs fed oxidised fats.     

Effects of high level of vitamin C on tissue antioxidant status of guinea pigs.

Two groups of weanling male Hartley guinea pigs maintained on vitamin E deficient diet were supplemented with 0.4 I.U./100 g body weight/day of vitamin E and either 2 (Group A) or 10 (Group B) mg/100 g body weight/day of vitamin C for 5 weeks. As compared to Group A, the degree of erythrocyte hemolysis and liver TBAR level of Group B were significantly increased while plasma vitamin E and erythrocyte GSH levels were significantly decreased. In another experiment, two groups of guinea pigs were given 0.8 I.U./100 g body weight/day of vitamin E and 2 (Group C) or 30 mg/100 g body weight/day (Group D) of vitamin C. Levels of plasma vitamin E and erythrocyte GSH of Group D were significantly lower than those of Group C: however, erythrocyte hemolysis and liver TBAR were not affected by the level of vitamin C supplementation. The results suggest that the high levels of vitamin C supplementation lowered tissue antioxidant potential of animal when vitamin E was marginally adequate, and the hemolytic and peroxidizing effect of high level of vitamin C may be counteracted by increasing the level of vitamin E.     

沙棘籽油对大鼠溃疡性结肠炎组织的保护作用及其机制

  目的  探讨不同剂量维生素C（VC）联合维生素D₃（VD₃）对结肠炎豚鼠肠粘膜通透性的影响。  方法  24只雄性Dunkin-Hartley豚鼠适应性喂养7 d后,按体重随机分为4组,每组6只：对照组（100 mg/kg VC）、模型组（100 mg/kg VC）、低、高剂量VC组（10、200 mg/kg VC）,采用改良豚鼠灌胃方法给予各组豚鼠剂量为200 IU/kg的VD₃,同时按组别给予相应剂量VC,连续5周;模型组、低、高剂量VC组豚鼠自由饮用2 %葡聚糖硫酸钠（DSS）溶液4 d,对照组豚鼠自由饮用蒸馏水。采用放射免疫法检测血清中25-（OH）D₃和1, 25-（OH）₂D₃水平,酶联免疫法检测血清中二胺氧化酶（DAO）、D–乳酸和内毒素含量;取远端结肠组织,常规石蜡包埋,苏木素–伊红（HE）染色,显微镜下观察,进行组织病理学评分。  结果  与对照组比较,模型组、低、高剂量VC组豚鼠结肠大体形态评分和组织病理学评分均明显升高（P < 0.05）;与对照组比较,模型组、低、高剂量VC组豚鼠血清中DAO含量[分别为（252.02 ± 1.74）、（253.06 ± 2.54）（250.60 ± 0.82）U/mL]均明显升高（P < 0.05）,低、高剂量VC组豚鼠血清中内毒素水平[分别为（109.74 ± 13.37）、（111.58 ± 12.49）EU/mL]均明显降低（P < 0.05）。  结论  在一定剂量的维生素D₃基础上,VC对结肠炎豚鼠肠粘膜屏障功能具有一定保护作用。     

Erythorbic acid content in tissues of guinea pigs administered erythorbic acid

The erythorbic acid (ErA) content in the tissues of guinea pigs administered ErA was compared with that of ascorbic acid (AsA). Guinea pigs were administered 1, 5, 20, and 100 mg ErA/day or 1, 5, and 100 mg AsA/day for 16 days and then sacrificed. The liver, adrenal glands, spleen, and kidneys were removed to determine the contents of ErA and AsA using HPLC. Only a small amount of ErA was found in four tissues of the animals administered 20 mg or more of ErA/day. On the contrary, AsA was found in the tissues of all animals administered 1 mg or more of AsA/day. The ErA content in the tissues was much lower than that of AsA even when the amount of ErA administered was the same as that of AsA. However, the body weight gains of animals administered ErA were similar to those of animals administered AsA. These observations suggested that the mechanism of the retention of ErA in the tissues was much different from that of AsA and that the vitamin C activity of ErA might be more than one-twentieth that of AsA.     

A subtoxic interactive toxicity study of ethanol and chromium in male Wistar rats.

The purpose of this study was to evaluate the interactive toxicity of ethanol with potassium dichromate (K2Cr2O7-chromium). Young, male Wistar rats (100-120 g) were divided into four groups of five or six animals each and were dosed, through water, with 10% ethanol (vol./vol.) or 25 ppm chromium or were dosed with a combination of ethanol+chromium at the same concentrations for a period of 22 weeks ad libitum and were maintained on normal diet. Control animals were maintained on a normal diet and water for the same period. The serum succinate dehydrogenase and liver total triglyceride levels were significantly reduced in the three treated groups. The serum alkaline phosphatase levels were significantly reduced in ethanol-treated rats, and there was no significant change in the acid phosphatase activity. Serum aspartate and alanine aminotransferase levels in the three treated groups were significantly increased. The liver glycogen significantly decreased in both the ethanol-treated and the chromium-treated rats. There was a significant increase in liver total cholesterol levels in chromium-treated rats. Total glutathione levels were significantly decreased in the livers of ethanol-treated and ethanol+chromium-treated rats. To further substantiate these findings, a histological examination of the liver and kidneys was undertaken. The livers of alcohol-treated animals showed altered hepatic architecture in the centrilobular and periportal areas, with increased sinusoidal space (space of Disse), vacuolation, and necrosis of hepatocytes. Similar changes were observed in a histological examination of the livers of chromium-treated rats, except that the damage to the hepatocytes was more confined to the periportal area. Moreover, histological examination of the livers of ethanol+chromium-treated rats revealed uniform damage in the centrilobular and periportal areas, as was observed in the groups treated either with ethanol or chromium. The histological examination of the kidneys in the three treated groups revealed significant damage to the renal tubules and Bowman's capsule, which showed vacuolation and degeneration of the basement membrane. These findings correlate well with the serum enzyme levels found in the treated groups. It is evident from this study that chronic ethanol consumption sensitizes the liver to the toxic action of agents such as chromium. It leads to impairment of the biochemical functions in the liver, and it causes liver and kidney damage. Long-term simultaneous exposure to ethanol and chromium may cause severe health problems in people who are alcoholics and work in chrome-plating and leather-tanning industries.     

Effect of oxidized frying oil and vitamin C levels on the hepatic xenobiotic-metabolizing enzyme system of guinea pigs

The influence of oxidized frying oil (OFO) on the guinea pig hepatic microsomal xenobiotic-metabolizing enzyme system in the presence of different amounts dietary vitamin C was investigated. Weanling male guinea pigs were divided into four groups and were fed 15% oxidized frying oil diets supplemented with vitamin C at 300, 600, or 1,500 mg/kg (experimental diets) or a control diet that contained 15% fresh untreated soybean oil with 300 mg/kg of vitamin C, respectively. After 60 d, guinea pigs were euthanized and phase I and phase II xenobiotic-metabolizing enzymes in the liver were determined. Compared with the fresh oil diet fed the control group, the relative liver weight was higher in the OFO-fed groups. Hepatic microsomal protein and cytochrome P450 contents were significantly higher in OFO-fed guinea pigs than in the control group. Both values increased in response to increased intake of vitamin C. The activities of phase II relative components, including UDP-glucuronyl transferase, UDP-glucuronyl dehydrogenase and beta-glucuronidase, of guinea pigs fed the OFO diets supplemented with 300 mg vitamin C/kg were significantly higher than those of guinea pigs fed the control diet. However, the phase II relative components decreased with increasing vitamin C content in the diet. The results demonstrate that both dietary OFO and vitamin C in guinea pigs induce hepatic xenobiotic-metabolizing enzymes, but the level of induction is modulated by the dietary vitamin C level.     

Contribution of a high dose of L-ascorbic acid to carnitine synthesis in guinea pigs fed high-fat diets.

Ascorbate is a cofactor of two-enzyme hydroxylation in the pathway of carnitine biosynthesis. The purpose of this study was to investigate the contribution of ascorbate to endogenous carnitine in guinea pigs fed high-fat diets. The contents of carnitine in plasma, urine and tissues of guinea pigs supplemented with L-ascorbic acid were determined and compared with those supplemented with carnitine. Albino-Hartley guinea pigs were fed vitamin C-deficient diets containing lard throughout the experiment. They were administered orally with 5 mg L-ascorbic acid/d/animal for 14 d, and then divided into three groups and administered orally with the following supplements (/d/animal) for 14 d; L (5 mg L-ascorbic acid), LASA (100 mg L-ascorbic acid), and LCAR (10 mg carnitine plus 5 mg L-ascorbic acid). As a control, a normal group was fed vitamin C-deficient diets and administered orally with 5 mg L-ascorbic acid/d/animal for 28 d. The animals fed high-fat diets (L group) had higher free-carnitine contents in the muscle and urine than the normal group. The groups of LCAR and LASA had significantly higher contents of acid-soluble carnitine (p < 0.05) in plasma than the L group. Urinary excretion of carnitine in the LASA group was decreased to the same level as that in the normal group, although no significant difference between the groups of L and LCAR was observed. Moreover, the supplement of ascorbic acid, but not of carnitine, induced a significantly lower content of triacylglycerol in the plasma of the LASA group as compared to the L group (p < 0.05). These data suggest that high doses of ascorbic acid in guinea pigs fed high-fat diets contribute to the enhancement of carnitine synthesis and improvement of the triacylglycerol content in the plasma.     

Ascorbic acid synthesis in certain guinea pigs.

Three guinea pigs fed a vitamin C-free diet manifested no symptoms of scurvy even after 4-8 months, normally increased in body weight and excreted quantities of ascorbic acid in urine far exceeding the total body pool of ascorbic acid. The course of healing subsequent to experimental trauma in one of these animals proved to be entirely normal and vitamin C concentration in its liver after 8 months of a scorbutogenic regimen was found to be more than twice that in guinea pigs with a daily intake of 10 mg ascorbic acid. It is evident that certain guinea pigs are capable to synthesize ascorbic acid that fully covers the needs of the organism. However, the freqency of occurence of such guinea pigs appears to be extremely small.     

Effect of cholesterol feeding on tissue lipid perioxidation, glutathione peroxidase activity and liver microsomal functions in rats and guinea pigs.

The effect of cholesterol feeding on liver and aortic nonenzymatic lipid peroxidation and glutathione peroxidase activities, and on liver microsomal NADPH-dependent lipid peroxidation, codeine hydroxylation and cytochrome P-450 levels was examined in rats and guinea pigs. One percent cholesterol was added to a casein-sucrose-soybean oil basal diet for rats or a stock diet with 2% soybean oil for guinea pigs. The effect of vitamin E and cholestyramine was also examined in some experiments. Cholesterol feeding increased the rate of lipid peroxidation in liver and aortic homogenate both in rats and guinea pigs when fed non-vitamin E supplemented basal diets. Vitamin E supplementation prevented the increase in the aorta, but not as completely in the liver in rats, while the reverse was true in guinea pigs. The effect of cholestyramine was dependent on the level of vitamin E in the diet. Cholesterol feeding decreased glutathione peroxidase activities in rats and guinea pigs. In guinea pigs, cholesterol feeding also markedly decreased liver microsomal NADPH-dependent lipid peroxidation, codein hydroxylation and cytochrome P-450 levels especially when fed non-vitamin E supplemented basal diets. In rats, cholesterol feeding reduced liver microsomal NADPH-dependent lipid peroxidation and in some cases, increased microsomal codeine hydroxylation activities, but had no effect on microsomal cytochrome P-450 levels. Vitamin E supplementation increased liver and serum cholesterol levels in guinea pigs, but had no such effect in rats. Results of this study indicate that cholesterol feeding can result in various metabolic alterations in rats and guinea pigs. The implication of these alterations in atherogenesis requires further investigations.     

Activity of chosen indicator enzymes in blood serum of guinea pigs exposed to ethyl- and phenylmercuric chloride alone or jointly with sodium selenite

The effect of sodium selenite on the activity of the selected enzymes in blood serum and on mercury concentration in some tissues of guinea pigs exposed to ethyl- (EtHg) or phenylmercuric chloride (PhHg) was investigated. Every second day for a 3-month period animals were given intragastrically a solution of mercuric compounds (2.5 mg Hg/kg) with or without sodium selenite (1 mg Se/kg). The activity of malate dehydrogenase (MDH, EC 1.1.1.37), phosphohexoizomerase (PHI, EC 5.3.1.9), and gamma-glutamyltranspeptidase (GGTP, EC 2.3.2.2) in blood serum of control animals was ca. 3.8, 325, and 48 IU. After 10 weeks of exposure to EtHg and PhHg, the activities (IU) of the above enzymes were, respectively, 5.9 and 6.5 (MDH), 585 and 600 (PHI) and 211 and 86.5 (GGTP). Sodium selenite administered with mercuric compounds did not prevent in increases in enzyme activity. During the experiment the level of inorganic as well as organic mercury accumulated in kidneys and liver was estimated. After a 12-week exposure, sodium selenite decreased the level of total mercury in the liver (in the case of both EtHg and PhHg: from 47.0 to 31.8 and from 41.3 to 25.4 micrograms Hg/g tissue, respectively). It also slightly decreased the mercury level in the kidneys of animals exposed to PhHg (from 889 to 73.3 micrograms Hg/g tissue) but did not change the mercury concentration in the kidneys of guinea pigs exposed to ethylmercuric chloride.     

Antiscorbutic effect of dehydro-L-ascorbic acid in vitamin C-deficient guinea pigs

The antiscorbutic effect of dehydro-L-ascorbic acid (DAsA) was investigated in vitamin C-deficient guinea pigs. Male guinea pigs were fed vitamin C-deficient diets for 16 days to deplete body L-ascorbic acid (AsA) pools and then fed the deficient diet supplemented with DHA and/or AsA intraperitoneally for 14 days. During the repletion period, most of the animals injected with 0.5 mg DAsA/day developed scurvy, their body weights decreased and their mortality rate was higher than that of the other groups injected with 0.5 mg AsA/day or 5 mg DAsA/day. Injecting animals with 0.5 mg AsA/day resulted in the disappearance of the typical scorbutic symptoms and regaining of body weight. These data indicate that DAsA has considerably less antiscorbutic activity than AsA in vitamin C-deficient guinea pigs.     

Vitamin C lowers mutagenic and toxic effect of hexavalent chromium in guinea pigs

The mutagenic effect of intraperitoneally injected K2Cr2O7 was significantly higher in vitamin C-deficient guinea pigs than in animals fed diet with high vitamin C content. Mutagenic and toxic effects of hexavalent chromium were more expressed in vitamin C-deficient guinea pigs administered K2Cr2O7 in drinking water: the number of micronuclei in polychromatic erythrocytes of bone marrow was increased, and the activity of O-demethylase and the levels of cytochromes P-450 and b5 in liver microsomes were decreased. In guinea pigs fed high vitamin C diet the same doses of bichromate in drinking water evoked no mutagenic changes in the bone marrow and no changes in microsomal enzymes in the liver. These results indicate that high intake of ascorbic acid in the diet reduces mutagenic effects of K2Cr2O7 and its toxic influence on drug metabolizing enzymes in hepatocytes. The protective effect ascorbic acid consists most probably in the enhanced extracellular and intracellular reduction of hexavalent chromium to the less toxic and less mutagenic trivalent chromium.     

Vitamin C activity of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid in guinea pigs.

The vitamin C activity of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), which is one of chemically stable derivatives of L-ascorbic acid (AsA), in guinea pigs was investigated. Male guinea pigs were divided into 9 groups and fed AsA-deficient diet for 24 days with the following supplement: AA-2G- or AsA-supplemented groups were orally supplemented with 0.96, 1.92, 9.6 and 192 AA-2G mg/animal/day or equimolar amounts of AsA (0.5, 1, 5 and 100 mg/animal/day, respectively); AsA-deficient group received neither of them. The body weight gain, serum alkaline phosphatase activity, and the concentration of AsA and AA-2G in the liver, adrenals and urine of the guinea pigs were measured at the end of the experimental period. The AA-2G-supplemented guinea pigs showed similar body weight gain to the animals supplemented with equimolar amount of AsA. Serum alkaline phosphatase activity in both AA-2G- and AsA-supplemented groups was significantly higher than that of AsA-deficient group. But there was no significant difference between the groups supplemented with AA-2G and the equimolar amount of AsA. AA-2G-supplemented guinea pigs showed no apparent symptoms of scurvy. In AA-2G-supplemented groups, AA-2G was not detected in the liver, adrenals and urine, but AsA was found and the AsA concentration increased with increasing AA-2G dosage. The AsA concentration in the tissues of each AA-2G-supplemented groups was higher than that of AsA-deficient group, which was similar to that of the groups supplemented with equimolar amount of AsA. These results showed that AA-2G has the same vitamin C activity as AsA on a molar basis for the orally supplemented guinea pigs.