Comparison of the effects of carbamyl phosphate and sodium cyanate on protein synthesis and glutathione concentration in human sickle cell and rabbit reticulocytes.
Two carbamylating agents, carbamyl phosphate and sodium cyanate, are currently being evaluated as therapeutic drugs for the treatment of sickle cell anemia. Since the clinical usefulness of these drugs might be limited by toxicity, a comparative in vitro study of the relative inhibition of human sickle cell and rabbit reticulocyte protein synthesis was performed. Sodium cyanate was found to inhibit human sickle cell protein synthesis at concentrations one-eighth that of carbamyl phosphate. Carbamyl phosphate lowered reduced glutathione levels to a similar degree as sodium cyanate and was slightly more effective as an in vitro antisickling agent, which is evidence that carbamyl phosphate enters these cells. When rabbit reticulocyte protein synthesis was investigated, carbamyl phosphate was found to be noninhibitory at concentrations as high as 128 mol/mol of hemoglobin in the incubation medium, while cyanate was inhibitory at much lower concentrations. The effect of carbamyl phosphate on glutathione concentrations, however, was virtually identical to that of cyanate. These results show that the effect on protein synthesis does not result from the lowered glutathione levels. It is concluded that both the therapeutic and toxic effects of sodium cre, there might be differences in toxicity between animals and humans.
D000755:Anemia, Sickle Cell / Q000097:blood*; D000818:Animals; D001798:Blood Proteins / Q000096:biosynthesis*; D002219:Carbamates / Q000494:pharmacology*; D002221:Carbamyl Phosphate / Q000494:pharmacology*; D003485:Cyanates / Q000494:pharmacology*; D003864:Depression, Chemical; D004913:Erythrocytes, Abnormal / Q000378:metabolism; D005978:Glutathione / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D007930:Leucine / Q000097:blood; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism*; D013997:Time Factors
D001798:Blood Proteins; D002219:Carbamates; D003485:Cyanates; D002221:Carbamyl Phosphate; D005978:Glutathione; D007930:Leucine