ASCORBIC ACID REQUIREMENTS AND METABOLISM IN RELATION TO ORGANOCHLORINE PESTICIDES^*

Abstract

Those organochlorine pesticides which possess both high lipoid solubility and high resistance to biodegradation are prone to accumulation in animal tissues and produce relatively long-term effects as toxicants. Such compounds, typified by DDT, Dieldrin, and Lindane, are profound inducers of hepatic microsomal enzymes, including parts of the glucuronic acid and ascorbic acid biosynthetic pathways. Consequently, administering such pesticides to rats in accompanied by enhanced formation and excretion of D-glucuronic acid and L-ascorbic acid, or D-glucaric acid in the case of guinea pigs. Secondarily, the efficiency in biodegrading the pesticides is reduced in ascorbic-acid-deficient guinea pigs with correspondingly greater residue accumulation in tissue. This would aggravate chronic toxic effects of the compounds. Finally, the capacity of the liver to adapt to the presence of such toxicants through enhanced microsomal enzymatic levels appears to be sensitive to its ascorbate status. Impaired enzyme induction is apparent quite early during ascorbic acid depletion in guinea pigs. The enhanced turnover of ascorbate produced by such pesticides, the poor enzymatic adaptation to them during ascorbate depletion and the dependency of the oxidase system upon adequate ascorbate, all point to the central significance of ascorbate status in the liver, and possibly other tissues, as a determinant of their chronic toxicity.

Role of the vitamin C in diethylnitrosamine-induced esophageal cancer in Wistar rats

“…The data obtained by the present study are in accordance with the theory that the vitamin C inhibits strongly the esophageal carcinogenesis (Figure 2) 18,22,28 . Studies demonstrated the direct effect vitamin C on carcinogen blockade, such as the conversion of the benzopyrene and anthracene to less poisonous substances 27 , the inactivation of organochlorine pesticides 27 , and the prevention of the oxidative lesions from ozone and hydrogen oxide in association which vitamin D 28 . In spite of being consistent and exciting, some aspects should be considered.…”

“…In sperm studies it was already demonstrated the capacity of the vitamin C for protecting DNA from oxidative lesions. Considering that vitamin C is an antioxidant, it would act by supplying electrons for neutralization of the free radicals 25,26,27,28 . Oliveira et al 29 studied the antioxidant effects vitamin C in experimental gastric cancer model induced in Wistar rats (30 mg/Kg/day) and they found reduction of oxidative stress and gastric tumor incidence.…”

Tissue Levels and Optimum Dosage of Vitamin C in Guinea Pigs

“…This conclusion draws support, not only from data on lipid metabolism described in the present study, and those reported by other authors (13,14,19), but also from data on the effect of graded ascorbate levels in tissues on the rate of hydroxylation of a variety of pharmaceutical agents and environmental chemicals (25,27,29), on the rate of 14C-proline hydroxylation in granuloma (23), on amine-nitrite toxicity (16) and on the prevention of cholesterol gallstone formation in guinea pigs (10).…”

Influence of some environmental variables on the ascorbic acid status of mullet, Mugil cephalus L., tissues

“…AsA is involved in detoxification mechanisms as a cofactor for cytochrome P-450 (Zannoni & Sato, 1975), in the detoxification of histamine (Chatterjee ef al., 1975b), and in the induction of the glucuronic acid pathway (Street & Chadwick, 1975). The present data suggest that the toxic effects of environmental contaminants may be exacerbated at the end of the winter when there are insufficient AsA reserves to meet these additional demands.…”