Ascorbic acid requirements and metabolism in relation to organochlorine pesticides.
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.
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001206:Ascorbic Acid Deficiency / Q000378:metabolism; D001835:Body Weight; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003634:DDT / Q000494:pharmacology / Q000633:toxicity; D004026:Dieldrin / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005965:Glucuronates / Q000652:urine; D006168:Guinea Pigs; D001556:Hexachlorocyclohexane / Q000494:pharmacology / Q000633:toxicity; D007306:Insecticides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D051381:Rats
D005965:Glucuronates; D007306:Insecticides; D008112:Liver Glycogen; D001556:Hexachlorocyclohexane; D003577:Cytochrome P-450 Enzyme System; D003634:DDT; D004026:Dieldrin; D001205:Ascorbic Acid