We have investigated the effect of a diet containing of 4 % oyster fungus (Pleurotus ostreatus) and 0.1 % cholesterol on glycaemia and hyperlipoproteinaemia in rats with insulin-dependent diabetes (streptozotocin 45 mg/kg). After two months, the rats with diabetes kept on the oyster fungus diet, had a significantly lower basal and postprandial glycaemia, the insulinaemia remained unchanged. The cholesterol concentration was decreased by more than 40 %, the lipoprotein profile was upgraded by the decrease of the cholesterol in both the low density and very low density lipoproteins. The oyster fungus decreased the cholesterol accumulation in the liver and had no significant effects on the levels of serum and liver triacylglycerols.
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.
Changes in serum and liver lipids, hepatic ascorbic acid (AA) and cytochrome P-450 were investigated in female guinea pigs divided into three groups with different AA intake in drinking water (10, 100 and 1000 mg AA per liter) for 10 weeks. Serum and liver total cholesterol significantly decreased in guinea pigs receiving 100 and 1000 mg AA per liter of drinking water when compared with guinea pigs with suboptimal AA intake (10 mg/1). Similarly, serum triglycerides were decreased in the groups with higher AA intake. Liver AA concentration increased significantly in accordance with rising AA doses. High AA intake (1000 mg/I) for 10 weeks resulted in significant increase of both cytochromes P-450 and cytochrome b5 and total haeme content in liver microsomes when compared to guinea pigs with suboptimal AA intake. A significant positive correlation between hepatic AA concentration and cytochrome P-450 content was observed. A close negative correlation between liver total cholesterol and cytochrome P-450 content in hepatic microsomes was also seen. Long-term suboptimal AA intake may unfavourably alter the blood and liver lipid profile as well as the capacity of hepatic drug metabolizing enzymes in both male and female guinea pigs.
The influence of regular moderate ethanol consumption on the status of vitamin C was followed in guinea-pigs and rats. In the guinea-pigs examined, 10-day consumption of ethanol (4.5 g per day and kg of body weight), administered in drinking water under a vitamin C-deficient diet, caused a greater decrease in the tissue concentrations and the body-pool of this vitamin than in the group without alcohol. In the rats, on the contrary, the daily consumption of ethanol (6 % vol) during 10 months resulted in an increase in the body stores of vitamin C, especially in the liver, adrenals, kidneys, and lungs. Moreover, the biosynthesis of ascorbate from D- glucuronolactone in vitro was more intensive (by 30 %) in the liver microsomes of alcoholized rats than in those of controls (without alcohol). These results indicate that the need of vitamin C during chronic consumption of moderate alcohol doses is enhanced. This is due to the participation of ascorbate in oxidoreducing processes connected with ethanol metabolism which leads to its irreversible destruction. In the rat, this loss is compensated by its enhanced biosynthesis, while in the guinea-pig it produces increased demands for its exogenous intake. If these are not satisfied, a partial vitamin C deficiency may occur, which potentiates the harmful effect of alcohol on the health status.
The oxidative modification of low density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis. LDL of subjects with atherogenic lipoprotein phenotype (ALP) is known to be more susceptible to oxidation. We studied the effect of the hypolipidaemic drug ciprofibrate on the susceptibility of LDL to in vitro oxidation. Nine patients with primary hypertriglyceridaemia and hypoalphalipoproteinaemia (mean plasma triglycerides 3.76 mmol.L1 and HDL-cholesterol 0.74 mmol.l-1) were treated with ciprofibrate for 12 weeks. The susceptibility of LDL to in vitro Cu2 +-mediated oxidation was assessed by measuring conjugated diene formation at 234 nm. Ciprofibrate therapy significantly prolonged the lag time (93±7 min vs. 102±11 min, P = 0.02). The maximal rate of diene production was 11 % lower, but the decrease was not significant. A significant positive correlation was observed between maximal rate and maximal amount of dienes formed. Thiobarbituric acid reacting substances (TBARS) and lipid hydroperoxides (LPO) in oxidatively-modified LDL, isolated from the plasma of patients before and after drug treatment, were unchanged. The results suggest that ciprofibrate therapy has a favourable effect by increasing the in vitro resistance of LDL against oxidation.
Apparently healthy free-living (non-hospitalized) men aged 8-89 years (n=408) were studied to determine the effect of age on serum copper and zinc concentrations and the copper/zinc ratio. Mean values ± S.D. for age, serum copper and zinc levels and the copper/zinc ratio were as follow: 41.9 ±22.9 years, 1.15 ± 0.17 ¿rg/ml, 0.93±0.14 /¿g/ml and 1.25±0.19, respectively. In the elderly subjects above 75 years, a marked increase in serum copper concentrations and the copper/zinc ratio as well as a decrease in serum zinc concentrations were observed. Serum copper concentrations and the copper/zinc ratio correlated positively with age (pcO.OOOl).
Chlorophenols, mainly used as biocides, are compounds with a wide spectrum of toxic effects including teratogenic and carcinogenic actions. In this study, the effects of 2,4-dichlorophenol (2,4-DCP) on hepatic microsomal cytochrome P-450, NADPH-cytochrome c reductase activity, liver ascorbic acid (AA) and glutathione (GSH) content were studied in guinea-pigs with a low (2 mg/day/animal) or a high (50 mg/day/animal) ascorbic acid intake. The high AA intake significantly increased liver AA and GSH levels. There was a clear-cut correlation between liver AA and GSH levels. Administration of 2,4-DCP significantly decreased cytochrome P-450 and f iADPH-cytochrome c reductase activity in hepatic microsomes isolated from guinea-pigs with the low AA intake. Such a reduction was not observed in intoxicated guinea-pigs with the high AA intake. The results suggest that AA can play a protective role in 2,4-DCP toxicity.