RESUMO

Glutathione (GSH) combines with several xenobiotics and its electrophilic metabolites enhancing their elimination in bile and urine. Thus protects cells by preventing binding of these labile intermediary with vital molecules. Some individuals may be susceptible to this deleterious effect according to the intracellular GSHB concentration. In the present study we intend to determine the extent and nature of interindividual variation of human lymphocyte glutathion contents, after oxidative stress with paracetamol. Intracellular basal GSH was measured after one hour of incubation in a cell culture medium additioned with rat liver microsomes and NADPH at 37 degrees C. Each time two batches of lymphocytes were measured in parallel, one without paracetamol (basal) and the other with paracetamol (paracetamol-depleted). In 90 normal adult Caucasians, mean basal GSH concentration of lymphocytes (22.3 mumol/10(7) cells) were higher than in a comparable group of 20 Chinese (19.1 mumol/10(7) cells) or 20 Blacks (17.9 mumol/10(7) cells) subjects. Paracetamol treated lymphocytes were depleted of GSH at the same rate in each group, thus the same differences seen in basal conditions persist post oxidative stress. Probit analysis of values for each ethnic group revealed only a single mode. In otherwise normal Caucasians males with Down's syndrome, mean basal GSH concentration (29.7 mumol/10(7) cells) were higher than those of Caucasians, Chinese and Blacks.

Assuntos

Acetaminofen/farmacologia , Glutationa/metabolismo , Linfócitos/efeitos dos fármacos , Grupos Raciais , Adulto , Relação Dose-Resposta a Droga , Humanos , Linfócitos/química , Linfócitos/metabolismo , Masculino , Estresse Oxidativo

RESUMO

Glutathione (GSH) combines with several xenobiotics and its electrophilic metabolites enhancing their elimination in bile and urine. Thus protects cells by preventing binding of these labile intermediary with vital molecules. Some individuals may be susceptible to this deleterious effect according to the intracellular GSHB concentration. In the present study we intend to determine the extent and nature of interindividual variation of human lymphocyte glutathion contents, after oxidative stress with paracetamol. Intracellular basal GSH was measured after one hour of incubation in a cell culture medium additioned with rat liver microsomes and NADPH at 37 degrees C. Each time two batches of lymphocytes were measured in parallel, one without paracetamol (basal) and the other with paracetamol (paracetamol-depleted). In 90 normal adult Caucasians, mean basal GSH concentration of lymphocytes (22.3 mumol/10(7) cells) were higher than in a comparable group of 20 Chinese (19.1 mumol/10(7) cells) or 20 Blacks (17.9 mumol/10(7) cells) subjects. Paracetamol treated lymphocytes were depleted of GSH at the same rate in each group, thus the same differences seen in basal conditions persist post oxidative stress. Probit analysis of values for each ethnic group revealed only a single mode. In otherwise normal Caucasians males with Downs syndrome, mean basal GSH concentration (29.7 mumol/10(7) cells) were higher than those of Caucasians, Chinese and Blacks.