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.
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.