RESUMO
Type 2 diabetes mellitus complicated by steatohepatitis is accompanied by a decrease in aconitate hydratase activity, increase in the content of diene conjugates, decrease in the concentration of α-tocopherol, and change in the citrate level in the blood serum of patients, which is evidence of the development of oxidative stress as a result of the intensification of free radical oxidation of biosubstrates and decreasing degree of antioxidant defense of the organism. Combined therapy with melaxen provided a more significant change of the investigated parameters toward the norm (on the average by 36%, p 0.05) in comparison with basic treatment. This result was evidently associated with implementation of the antioxidant effect of melatonin, the level of which is corrected under the action of the drug employed.
Assuntos
Aconitato Hidratase/sangue , Antioxidantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Melatonina/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Adulto , Idoso , Ácido Cítrico/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo/efeitos dos fármacos , alfa-Tocoferol/agonistas , alfa-Tocoferol/sangueRESUMO
We investigated the possible mechanisms of All-trans retinoic acid (ATRA)-promoted apoptosis induced by alpha-tocopherol succinate (alpha-TS) in freshly isolated leukemic cells obtained from chronic myeloid leukemic patients. alpha-TS at 50 microM concentration significantly decreased superoxide dismutase (SOD) activity and reduced glutathione (GSH) by 29% and 25%, respectively, and increased lipid peroxidation level by 33%. Though 10 microM ATRA did not affect these parameters, it further significantly enhanced alpha-TS-induced changes. Bax expression in the leukemic cells was increased by treatment with ATRA, alpha-TS, and their combination to 40%, 240%, and 320%, respectively, without any change in Bcl2 and p53 expression. C-myc was down regulated by treatment with ATRA, alpha-TS and their combination to 22%, 48.5%, and 52%, respectively. In conclusion, the data reveal that enhancement of alpha-TS-induced apoptosis by ATRA in leukemic cells was through up regulation of Bax and lipid peroxidation, and down regulation of c-myc and GSH.
