fluoride show increased levels of lipid peroxide (LPO) in the liver, serum, heart,
and kidneys, whereas the activities of SOD and GSHPx and the levels of GSH
were decreased. Administration of b-carotene (which can be partially
converted to vitamin A in the body) reduced LPO levels while raising SOD
activity.
21
The mechanism involved in vitamin A action relative to carcinogenesis may
in part involve a free-radical scavenging action of the vitamin. Because vitamin
A is required in the differentiation of epithelial cells (important in both
respiratory and gastrointestinal tracts), its deficiency may affect transformation
of epithelia and thus predispose the tissue to neoplastic changes.
5.8.7 VITAMIN D
The role that vitamin D plays in the prevention of rickets and osteomalacia has
been well documented. To play its role in the maintenance of Ca homeostasis,
vitamin D must be converted into its metabolically active form, 1,25dihydroxy-D 3 (the hormone-like substance). Vitamin D 3 (cholecalciferol) is
first hydroxylated in the liver to 25-hydroxy-D 3 . The resultant 25-hydroxy-D 3
is then converted in the kidney to 1,25-dihydroxy-D 3 , the active form of the
vitamin. The 25-hydroxylation of cholecalciferol requires NADPH, O 2 , and an
enzyme whose properties are similar to those of microsomal MFO.
22 In
addition, 25-hydroxy-D 3 has been shown to competitively inhibit some
cytochrome P450 reactions in vitro. Patients suffering from drug-induced
osteomalacia show increased rates of catabolism of vitamin D 3 to 25-hydroxyD 3 . In a recent laboratory study of male mice exposed to NaF, vitamin D,
alone or in combination with vitamin E, was found to ameliorate the adverse
effect of NaF on reproductive function and fertility.
23
5.8.8 VITAMIN E (a-TOCOPHEROL)
Vitamin E, a membrane-bound antioxidant and free-radical scavenger, appears
to offer protection against injuries caused by O 2 , O 3 , and NO 2 , and nitrosamine
formation. Male rats administered daily doses of 100 mg tocopheryl acetate
and exposed to 1.0 ppm O 3 were shown to survive longer than rats deficient in
vitamin E. The action of O 3 is attributed in part to formation of free radicals.
Vitamin E is also believed to protect phospholipids of microsomal and
mitochondrial membranes from peroxidative damage by reacting with free
radicals (Figure 5.4). Because lipid peroxidation is associated with decrease in
oxidase activities, it is expected that the enzyme activity is affected by dietary
vitamin E. Maximum activity has been observed when diets include both
polyunsaturated fatty acids and vitamin E.
Nitrosamine, known to be carcinogenic, leads to liver cancer. The
interaction between vitamin E and nitrosamines is attributed to the inhibitory
effect of the vitamin on nitrosamine formation, i.e., vitamin E competes for
nitrite, a reactant in nitrosamine formation.
Factors Affecting Xenobiotic Action
77
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Ref: 4365 MING-HO YU Chap-005 Page: 77 65-84
and kidneys, whereas the activities of SOD and GSHPx and the levels of GSH
were decreased. Administration of b-carotene (which can be partially
converted to vitamin A in the body) reduced LPO levels while raising SOD
activity.
21
The mechanism involved in vitamin A action relative to carcinogenesis may
in part involve a free-radical scavenging action of the vitamin. Because vitamin
A is required in the differentiation of epithelial cells (important in both
respiratory and gastrointestinal tracts), its deficiency may affect transformation
of epithelia and thus predispose the tissue to neoplastic changes.
5.8.7 VITAMIN D
The role that vitamin D plays in the prevention of rickets and osteomalacia has
been well documented. To play its role in the maintenance of Ca homeostasis,
vitamin D must be converted into its metabolically active form, 1,25dihydroxy-D 3 (the hormone-like substance). Vitamin D 3 (cholecalciferol) is
first hydroxylated in the liver to 25-hydroxy-D 3 . The resultant 25-hydroxy-D 3
is then converted in the kidney to 1,25-dihydroxy-D 3 , the active form of the
vitamin. The 25-hydroxylation of cholecalciferol requires NADPH, O 2 , and an
enzyme whose properties are similar to those of microsomal MFO.
22 In
addition, 25-hydroxy-D 3 has been shown to competitively inhibit some
cytochrome P450 reactions in vitro. Patients suffering from drug-induced
osteomalacia show increased rates of catabolism of vitamin D 3 to 25-hydroxyD 3 . In a recent laboratory study of male mice exposed to NaF, vitamin D,
alone or in combination with vitamin E, was found to ameliorate the adverse
effect of NaF on reproductive function and fertility.
23
5.8.8 VITAMIN E (a-TOCOPHEROL)
Vitamin E, a membrane-bound antioxidant and free-radical scavenger, appears
to offer protection against injuries caused by O 2 , O 3 , and NO 2 , and nitrosamine
formation. Male rats administered daily doses of 100 mg tocopheryl acetate
and exposed to 1.0 ppm O 3 were shown to survive longer than rats deficient in
vitamin E. The action of O 3 is attributed in part to formation of free radicals.
Vitamin E is also believed to protect phospholipids of microsomal and
mitochondrial membranes from peroxidative damage by reacting with free
radicals (Figure 5.4). Because lipid peroxidation is associated with decrease in
oxidase activities, it is expected that the enzyme activity is affected by dietary
vitamin E. Maximum activity has been observed when diets include both
polyunsaturated fatty acids and vitamin E.
Nitrosamine, known to be carcinogenic, leads to liver cancer. The
interaction between vitamin E and nitrosamines is attributed to the inhibitory
effect of the vitamin on nitrosamine formation, i.e., vitamin E competes for
nitrite, a reactant in nitrosamine formation.
Factors Affecting Xenobiotic Action
77
[16:54 26/8/04 P:/CRC PRESS/4365 MING-HO.751 (1670)/4365-005.3d]
Ref: 4365 MING-HO YU Chap-005 Page: 77 65-84