Toxicological screening models: drug-induced oxidative hemolysis.
In an attempt to obtain a simple screening system for the assessment of toxic-hemolytic effects of chemical substances, a battery of hematological tests was used. Phenacetin served as reference substance. The drug caused reversible formation of methemoglobin and Heinz bodies and an increase in peripheral reticulocytes after 2 and 4 weeks of treatment. Furthermore, an increase in the mean corpuscular volume of red blood cells (RBC) and the volume of RBC ghosts in hypotonic solutions, and a decrease of the mean corpuscular fragility was observed. The latter changes are considered to be a consequence of regenerative RBC compensation rather than due to structural membrane alteration caused by the drug. The results suggest that only a combination of several hematological tests can provide comprehensive information about the hemolytic potential of chemical substances, and that for screening purposes small numbers of animals are often sufficient.
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004909:Erythrocyte Indices / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D008297:Male; D008706:Methemoglobin / Q000032:analysis; D009996:Osmotic Fragility / Q000187:drug effects; D010084:Oxidation-Reduction; D010615:Phenacetin / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D008706:Methemoglobin; D010615:Phenacetin