RESUMO
Alpha-lipoic acid (ALA) has been used as a dietary supplement at different doses in patients with diabetes mellitus type 2 (T2DM) due to its antioxidant, anti-inflammatory, and hypoglycemic effects. However, the reports on the effects of ALA are controversial. For this reason, the purpose of the present study was to determine the effect of 600 mg/day of ALA on the markers of oxidative stress (OxS) and inflammation and RAGE in older adults with T2DM. A quasiexperimental study was carried out with a sample of 135 sedentary subjects (98 women and 37 men) with a mean age of 64 ± 1 years, who all had T2DM. The sample was divided into three groups: (i) experimental group (EG) with 50 subjects, (ii) placebo group (PG) with 50 subjects, and control group (CG) with 35 subjects. We obtained the following measurements in all subjects (pre- and posttreatment): glycosylated hemoglobin (HbA1c), receptor for advanced glycation end products (RAGE), 8-isoprostane, superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant status (TAS), and inflammatory (CRP, TNF-α, IL-6, IL-8, and IL-10) markers. Regarding the effect of ALA on HbA1c, a decrease was observed in the EG (baseline 8.9 ± 0.2 vs. posttreatment 8.6 ± 0.3) and the PG (baseline 8.8 ± 0.2 vs. posttreatment 8.4 ± 0.3) compared to the CG (baseline 8.8 ± 0.3 vs. six months 9.1 ± 0.3) although the difference was not statistically significant (p < 0.05). There was a statistically significant decrease (p < 0.05) in the blood concentration of 8-isoprostane in the EG and PG with respect to the CG (EG: baseline 100 ± 3 vs. posttreatment 57 ± 3, PG: baseline 106 ± 7 vs. posttreatment 77 ± 5, and CG: baseline 94 ± 10 vs. six months 107 ± 11 pg/mL). Likewise, a statistically significant decrease (p < 0.05) in the concentration of the RAGE was found in the EG (baseline 1636 ± 88 vs. posttreatment 1144 ± 68) and the PG (baseline 1506 ± 97 vs. posttreatment 1016 ± 82) compared to CG (baseline 1407 ± 112 vs. six months 1506 ± 128). A statistically significant decrease was also observed in all markers of inflammation and in the activity of SOD and GPx in the CG with respect to the EG and PG. Our findings suggest that the administration of ALA at a dose of 600 mg/day for six months has a similar effect to that of placebo on oxidative stress, inflammation, and RAGE in older adults with T2DM. Therefore, higher doses of ALA should be tried to have this effect. This trial is registered with trial registration number ISRCTN13159380.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Ácido Tióctico/uso terapêutico , Idoso , Antioxidantes/metabolismo , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Tipo 2/sangue , Ingestão de Energia/fisiologia , Feminino , Glutationa Peroxidase/sangue , Humanos , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Superóxido Dismutase/sangue , Ácido Tióctico/sangueRESUMO
A reproducible, rapid procedure for the determination of glutathione in human blood by micellar electrokinetic chromatography has been developed. Whole blood samples were deproteinized with 5% w/v sulfosalicylic acid (final concentration). After centrifugation, the supernatant was directly injected for analysis, without further derivatization. Separations were performed by using an uncoated capillary of 30 cm effective length and 50 microns internal diameter (ID), 50 mM Tris-HCl, 30 mM sodium dodecyl sulfate (SDS), pH 7.00, as running buffer, and 10-20 kV. On-line detection was carried out at 214 nm and a detection limit in the range of femtomoles was achieved. Under the same experimental conditions, we resolved a mixed standard solution containing glutathione in its oxidize and reduced forms, lipoamide and alpha-lipoic acid. The corresponding migration times were reproducible. The present method allows rapid determination of these compounds, which play a critical role in oxidative stress, in cellular defense against injurious agents and whose levels are related to the toxicology and metabolism of several toxins and drugs, such as antineoplastic agents.