Partial Reversal of the in Vivo Antimalarial Activity of DDS against Plasmodium Berghei by Induced Hyperglycemia

Richard J. CenedellaDepartment of Pharmacology, West Virginia University Medical Center, Morgantown, West Virginia 26506

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L. H. SaxeDepartment of Pharmacology, West Virginia University Medical Center, Morgantown, West Virginia 26506

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Earlier observations, in vitro, demonstrated that the ability of 4,4′-diaminodiphenylsulfone (DDS) to inhibit the glucose utilization of intraerythrocytic Plasmodium berghei is antagonized by elevation of medium glucose levels. In this study we observed that a single oral dose of DDS (100 mg per kg) was less effective in depressing malaria infections in chronically hyperglycemic mice (blood-glucose levels of about 1,000 mg %) than in normoglycemic mice. Unparasitized normoglycemic and diabetic mice possess similar whole-blood DDS levels during the 24 hr after oral dosage with 100 mg per kg of DDS. After treatment of normoglycemic, P. berghei-infected rats with a single oral dose of DDS (100 mg per kg), the parasitized blood cells removed from these animals 6 hours later consumed less glucose than identically parasitized cells from untreated rats. These observations support the possibility that DDS exerts a portion of its antimalarial activity in vivo through inhibition of utilization of intraerythrocytic parasite glucose.

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