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A possible mechanism of heinz body hemolytic anemia induced by DQ-2511, a new gastroprokinetic drug, in dogs.

Abstract
A previous study revealed that DQ-2511, a new gastroprokinetic drug, induced hemolytic anemia together with increased Heinz body formation, preceded by a marked decrease in erythrocyte reduced glutathione (GSH) content, after 2 weeks of dosing onward in dogs. In this study, the effect of DQ-2511 on erythrocytes in the early period of dosing, in comparison with that of beta-acetylphenylhydrazine (APHZ), was investigated to confirm the difference between this drug and APHZ in the mechanism of increased Heinz body formation. DQ-2511 and APHZ were administered orally to beagle dogs for 1 week at dose levels of 600 and 4 mg/ kg, respectively. Dogs receiving APHZ showed anemia after dosing for 7 days, together with an increase in methemoglobin and Heinz body formation after 3 days of dosing. In contrast, blood GSH, glutathione reductase, and gamma-glutamylcysteine synthetase were only slightly decreased after dosing for 7 days. In dogs treated with DQ-2511, erythrocyte GSH began to decrease after 1 day of treatment and was about 25% of the control value after 7 days; however, no changes were seen in blood glutathione reductase, GSH peroxidase, or gamma-glutamylcysteine synthetase level. Hepatic GSH was decreased slightly. In another experiment, SD rats were administered DQ-2511 and APHZ orally for 1 week at dose levels of 1600 and 15 mg/kg, respectively. Rats receiving DQ-2511 showed no anemia or any changes in erythrocyte GSH and Heinz body formation. In contrast, rats treated with APHZ showed a marked anemia and increases in Heinz body formation and erythrocyte GSH. These results demonstrate that DQ-2511 causes a marked decrease in GSH in dogs, resulting in Heinz body anemia, whereas APHZ induces Heinz body formation after a significant increase in methemoglobin, and suggest that impairment of the GSH redox cycle and synthetases of GSH are not involved in the decreased GSH after DQ-2511 treatment. This difference in effects on GSH content may indicate the existence of a species difference in the anemia induced by DQ-2511.
AuthorsH Ohno, M Nomura, K Watanabe
JournalFundamental and applied toxicology : official journal of the Society of Toxicology (Fundam Appl Toxicol) Vol. 32 Issue 2 Pg. 269-77 (Aug 1996) ISSN: 0272-0590 [Print] United States
PMID8921330 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Anti-Ulcer Agents
  • Benzamides
  • Phenylhydrazines
  • ecabapide
  • N(1)-acetylphenylhydrazine
Topics
  • Anemia, Hemolytic (chemically induced)
  • Animals
  • Anti-Ulcer Agents (administration & dosage, toxicity)
  • Benzamides (administration & dosage, toxicity)
  • Dogs
  • Drug Administration Schedule
  • Erythrocytes (drug effects)
  • Female
  • Male
  • Phenylhydrazines (toxicity)
  • Rats
  • Rats, Sprague-Dawley

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