The effect of low (1 mg/animal/day), medium (10 mg/animal/day) and high (100 mg/animal/day) intake of ascorbic acid on tissue lipid peroxidation (LPO) and the physical state of erythrocyte membranes was investigated in female guinea-pigs fed a vitamin E low diet. Animals were killed after 9-11 weeks and the blood, liver, lungs, kidneys and adrenals were analysed. The LPO was estimated by the determination of malondialdehyde with HPLC. The physical state of erythrocyte membranes was determined spectrofluorometrically and expressed as fluorescence polarization of membrane lipid specific probe 1,6-diphenyl-1,3,5-hexatriene. The LPO concentrations in the liver and adrenals of the group on a low vitamin C intake were significantly increased. A significant non-linear negative correlation between C vitamin levels and LPO concentrations was found in these tissues. The fluidity of erythrocyte membranes as a measure of their structural state was significantly lower in the group with a low intake of C vitamin. It is probable that the water-soluble antioxidants, such as vitamin C, act in the plasma as primary defense against oxidative stress if the radicals are formed initially in the aqueous phase of whole blood.
The effects of cadmium and simultaneous administration of cadmium and vitamin C on hepatic microsomal monooxygenase activities, conjugation enzyme activities and enzyme activities in the serum were investigated in hamsters. Cadmium, as cadmium chloride, was administered to hamsters in a subtoxic dose in drinking water (10 mg Cd per liter) for 10 weeks. The majority of hepatic microsomal monooxygenases and enzyme activities in the serum reflecting liver damage were not significantly affected by subchronic cadmium treatment. On the other hand, cytosolic glutathione S-transferase and serum alanine aminotransferase were significantly changed by cadmium and these changes were effectively eliminated by the simultaneous administration of vitamin C (1 g per liter of drinking water). The results indicate that long-term supplementation with vitamin C may be effective in the protection of hepatic enzymes against cadmium toxicity.
Guinea-pigs were maintained for 5 weeks on a diet containing three different concentrations of vitamin C: a) traces (none added), b) medium (0.05 % w/w) and high (0.5 % w/w). Twenty-four hours before killing the animals received one i.p. dose of 3 g ethanol per kg body weight (a model of short-term acute intoxication). In a parallel experiment which lasted 5 weeks, the animals were treated every week with two i.p. doses of 1 g ethanol per kg body weight followed bv the final acute intoxication (3 g ethanol/kg) (a model of long-term chronic alcoholization). In both experiments, the guinea-pigs with the highest tissue concentration of vitamin C proved to have significantly decreased residual levels of ethanol and acetaldehyde in the liver and the brain, a decreased activity of alanine- and aspartate aminoacyl transferases in the serum and decreased contents of triacylglycerols and cholesterol in the serum and liver in comparison with the vitamin C-unsupplemented group. The regression curve expressing vitamin C levels versus residual ethanol and acetaldehyde concentrations in the liver confirmed the highly significant negative correlation between them. Administration of the guinea-pigs with large amounts of vitamin C appears to accelerate ethanol and acetaldehyde metabolism and reduce some of their adverse health effects.
To investigate the effect of vanadyl trehalose (VT) on oxidative stress and reduced glutathione/glutathione-Stransferase（GSH/GSTs）pathway gene expression in mouse gastrointestinal tract, as well as the protective effects of vitamin C (VC) and reduced glutathione (GSH). Thirty male Kunming mice were randomly divided into five groups: control group (group A), VT group (group B), VC + VT group (group C), GSH + VT group (group D) and VC + GSH + VT group (group E). The content of reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) activity and the expressions of glutamatecysteine ligase catalytic subunit (GCLC), glutathione synthetase (GSS), regulated through glutathione reductase (GSR) and glutathione-S-transferase pi (GSTpi) in stomach and duodenum in vanadyl trehalose treated group were lower than those in group A (P<0.05). The C, D, E group can significantly improve the above indicators, but those only in the stomach in E group reached the level of the control group. Vanadyl trehalose (VT) was able to cause oxidative stress damage to the gastrointestinal tract of mice, which affects GSH content and GSH-Px activity and interferes with the normal expression of GSH/GSTs pathway. Exogenous vitamin C, reduced glutathione and the combination of the two could play a specific role in antioxidant protection and reduce the toxicity of vanadyl trehalose.
Cadmium in the dose of 1 mg/animal/day was administered to guinea-pigs in the form of CdCl2 dissolved in drinking water during short-term (5 weeks) and subchronic (12 weeks) experiments. Both the control and cadmium-treated groups were divided into two subgroups, according to low (2 mg/animal/day) and high (100 mg/animal/day) vitamin C intake. Subchronic cadmium treatment caused copper deficiency indicated by a dramatic decrease of copper concentration in the liver and serum and by its moderate decrease in the testes and brain. Cadmium significantly increased zinc concentrations in the kidneys during the whole experiment and decreased the level of zinc in the serum after subchronic cadmium treatment. In the control groups, the levels of zinc and copper in the serum were lowered after 5 weeks of high vitamin C doses. High doses of vitamin C in cadmium-treated guinea-pigs decreased the levels of copper in the testes, brain and serum. These observations suggest that cadmium intake in relatively high doses might potentiate the development of copper deficiency, and high doses of vitamin C aggravate, to a certain extent, copper depletion in some important organs and serum of guinea-pigs.