An evaluation of the dorset sheep as a predictive animal model for the response of glucose-6-phosphate dehydrogenase-deficient human erythrocytes to a proposed systemic toxic ozone intermediate, methyl oleate ozonide.
Erythrocytes of both glucose-6-phosphate dehydrogenase (G-6-PD)-deficient humans and Dorset sheep, an animal model with an erythrocyte G-6-PD deficiency, responded in a dose-dependent manner to the oxidant stress of methyl oleate ozonide (MOO) as measured by decreases in G-6-PD activity, increases in methemoglobin (METHB) levels, and decreases in GSH. However, the human G-6-PD-deficient erythrocytes were considerably more sensitive to the formation of METHB than the sheep erythrocytes while the reverse was the case for the GSH parameter. The results suggest a qualitative difference in the response of sheep erythrocytes and human G-6-PD-deficient erythrocytes to MOO that seriously questions the value of the sheep erythrocyte as a quantitatively accurate predictive model.
D000818:Animals; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008706:Methemoglobin / Q000378:metabolism; D009829:Oleic Acids; D010084:Oxidation-Reduction; D010126:Ozone / Q000494:pharmacology*; D012756:Sheep
D009829:Oleic Acids; C010235:methyl oleate ozonide; D010126:Ozone; D008706:Methemoglobin; D005978:Glutathione