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.
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 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.
In subjects with Down¢ s syndrome (DS) increased oxidative stress and consequent oxidative cell damage have been reported. The aim of this study was to assess whether the excessive production of free oxygen radicals in these subjects can affect the copper-induced lipid oxidation resistance measured in fresh whole serum. Since a significant elevation of serum uric acid levels, which is an efficient hydrophilic antioxidant, has been repeatedly reported in subjects with DS, we studied the association between increased serum uric acid levels and lipid resistance to oxidation measured directly in serum samples by monitoring the change in absorbance at 234 nm. The group of subjects with Down¢ s syndrome consisted of 25 individuals (aged 18± 5 years). Control group included brothers and sisters of subjects with DS (n = 25, aged 17± 7 years). In subjects with DS, the serum lipid resistance to oxidation (lag time) was significantly higher than in controls (p< 0.05) and a concomitant increase in serum uric acid levels was observed (p< 0.001). A significant positive correlation between lag time and serum uric acid concentration was found in subjects with DS (r = 0.48, p< 0.05), while the positive correlation in the control group was not significant. The results suggest that increased serum uric acid levels repeatedly observed in subjects with DS may be associated with an enhanced resistance of serum lipids to oxidation which is thought to play an important role in the atherogenic process., A. Nagyová, M. Šustrová, K. Rašlová., and Obsahuje bibliografii
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.