The effect of lead on oxidative hemolysis and erythrocyte defense mechanisms in the rat

Benjamin B. Gelman, I. Arthur Michaelson, James S. Bus

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40 Scopus citations

Abstract

The effect of chronic lead exposure on oxidative hemolysis and on biochemical defense mechanisms against such hemolysis was examined. The interaction between lead (Pb) and phenylhydrazine (PHZ) was studied using four groups of adult male rats treated with lead acetate in a combined oral-ip dosage regimen. After 27 days of exposure the blood lead (PbB) concentrations were (mean ± SD) 2.3 ± 1 (control), 33 ± 4, 67 ± 13, and 104 ± 17 μg/100 ml. On Day 27, PHZ (45 mg/kg sc) was administered to half of the rats in each group, and hemoglobin (Hb) and hematocrit (Hct) determinations were performed on tail blood drawn on Days 28, 29, 34, and 40. The results showed that in the acute hemolytic phase after PHZ both lead alone and PHZ alone reduced Hb and Hct but that the lead-PHZ interaction was not synergistic. A synergistic interaction did occur during the compensatory phase of anemia. The effect of in vivo lead exposure on in vitro hemolysis and biochemical defense mechanisms was studied in a second experiment, the results of which showed that lead caused a dose-dependent increase in oxidative hemolysis in vitro. Superoxide dismutase activity was decreased, whereas pentose shunt activity was increased. The effect of lead on reduced glutathione concentrations and glutathione peroxidase activity was biphasic, being increased at the intermediate dose but returning to baseline at the highest dose. We conclude that the in vivo interaction between Pb concentrations of up to approximately 100 μg/100 ml blood and oxidative hemolytic anemia was due to the ability of lead to inhibit compensatory hematopoiesis after an acute hemolytic episode. The more sensitive in vitro hemolysis test showed that lead caused a dose-dependent increase in oxidative hemolysis, and the biochemical changes observed were consistent with the hypothesis that in vivo lead exposure exerts a moderate pro-oxidant effect on rat erythrocytes.

Original languageEnglish (US)
Pages (from-to)119-129
Number of pages11
JournalToxicology and Applied Pharmacology
Volume45
Issue number1
DOIs
StatePublished - Jul 1978

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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