Mechanism of protein A-induced amelioration of toxicity of anti-AIDS drug, zidovudine.
Long-term treatment with 3-azido-3-deoxy thymidine (AZT) is often associated with myelosuppression. In AZT-treated Swiss mice, similar toxicological manifestations in terms of reduction of red blood and white blood cell counts and hemoglobin content had been observed as in AZT-treated AIDS patients. Pretreatment of animals with Protein A (PA) of Staphylococcus aureus Cowan I (1 microgram/ml), twice a week for two weeks, alleviated such hematopoietic toxicity due to AZT. AZT-induced reduction in colony-forming unit-erythroid (CFU-E) and colony-forming unit-granulocyte monocyte (CFU-GM) were also reversed by the combined treatment of AZT and PA. PA treatment showed an increased level of erythropoietin in the blood plasma, and cellularity of spleen, thymus, and bonemarrow was also increased in the group receiving combined treatment (PA+AZT), higher than that in the AZT group. AZT or its metabolites inhibited the activities of liver microsomal monooxygenases, which, however, could be regenerated in an accelerated manner by pretreatment of mice with PA. Moreover, the PA-treated group showed an accelerated clearance of AZT and/or its metabolites. These results suggest that such an immunopharmacologic approach might substantially reduce the toxic effects of drugs, such as AZT.
Subbulakshmi
V
V
Immunotechnology Section, Bose Institute, Calcutta-, 700 054, India.
Ghosh
A K
AK
Das
T
T
Ray
P K
PK
D000740:Anemia / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D007970:Leukopenia / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D051379:Mice; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D013205:Staphylococcal Protein A / Q000494:pharmacology*; D015215:Zidovudine / Q000009:adverse effects* / Q000037:antagonists & inhibitors
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D013205:Staphylococcal Protein A; D015215:Zidovudine