RESUMO
Mechanisms of myelotoxic action of Doxorubicin associated with changes in NAD(+)-glycohydrolase/CD38 expression and activity have been assessed. During the acute and subacute exposure of bone marrow cells to Doxorubicin in vivo, expression of CD38 is decreased corresponding to elevation of intracellular and extracellular NAD+ concentrations. These changes are associated with increased susceptibility of hemopoietic cells to the apoptogenic action of Doxorubicin. Possible role of NAD(+)-glycohydrolase/CD38 in the regulation of sensitivity of the cells to the cytotoxic effects of the xenobiotic is discussed.
Assuntos
ADP-Ribosil Ciclase 1/biossíntese , Antibióticos Antineoplásicos/toxicidade , Doxorrubicina/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Glicoproteínas de Membrana/biossíntese , NAD/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Masculino , Camundongos , Xenobióticos/farmacologia , Xenobióticos/toxicidadeRESUMO
A method is developed for estimation of the catecholamine-O-methyl transferase activity in human organism by excretion with urine of unmetabolized isadrine (N-isopropyl noreadrenaline) after loading. Excretion of isadrine was increased both after administration of apomorphine, which is one of the inhibitors of the enzyme catecholamine-O-methyl transferase, and in cases of liver tissue pathology. It is known that the maximal activity of catecholamine-O-methyl transferase is the highest in liver tissue. Imipramine (an inhibitor of uptake of catecholamine) did not inhibit the activity of cafecholamine-O-methyl transferase as estimated by the present method.
