Pyruvate and lactate metabolism in livers of guinea pigs perfused with chelating agents after repeated treatment with As2O3.
The relative effectiveness of British Anti-Lewisite (BAL), dimercaptopropanesulfonic acid (DMPS), dimercaptosuccinic acid (DMSA), and a new metal binding agent 2,3-bis(acetylthio)propanesulfonamide (BAPSA) was compared by determining their effect on pyruvate metabolism in perfused livers of guinea pigs after repeated treatment with As2O3. Guinea pigs received As2O3, 2.5 mg/kg s.c. twice daily on 5 consecutive days (total dose 25 mg/kg). Sixteen hours after the last dose the livers were perfused (2.5 ml/min/g liver) with Krebs-Henseleit buffer and glucose (10 mmol/l) as substrate for 80 min. After 50 min of perfusion 0.1 or 0.7 mmol/l BAL, DMPS, DMSA, or BAPSA were added to the perfusate for 30 min. Samples of the effluent were collected every 10 min; lactate and pyruvate were determined enzymatically. As compared to controls, a significant decrease in the pyruvate and lactate efflux was observed in perfused livers of guinea pigs treated with As2O3. After influx of BAL (0.1 mmol/l), DMSA (0.7 mmol/l), and BAPSA (0.1 and 0.7 mmol/l) respectively, the pyruvate and lactate efflux and the oxygen consumption (exception BAL 0.1 mmol/l) increased and reached control values without arsenic treatment. On the other hand, the pyruvate and lactate efflux and the oxygen consumption was further significantly decreased after influx of 0.7 mmol/l BAL.
Reichl
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Walther Straub-Institut für Pharmakologie and Toxikologie, Ludwig-Maximilians-Universität München, Federal Republic of Germany.
Kreppel
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Forth
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D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D001151:Arsenic / Q000633:toxicity*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D002614:Chelating Agents / Q000494:pharmacology*; D004112:Dimercaprol / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010087:Oxides; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D004113:Succimer / Q000494:pharmacology
D000931:Antidotes; D001152:Arsenicals; D002614:Chelating Agents; D007773:Lactates; D010087:Oxides; D011773:Pyruvates; D004112:Dimercaprol; D019344:Lactic Acid; D019289:Pyruvic Acid; D004113:Succimer; D001151:Arsenic; D000077237:Arsenic Trioxide