Efeito da suplementação de cisteína ou glutamina sobre o metabolisno dos aminoácidos sulfurados e glutationa de pacientes infectados pelo HIV nas condições de jejum e pós-sobrecarga de metionina / Effect of the cysteine or glutamine supplementation on the metabolism of sulphurated amino acids and glutathione state of HIV patients on fasting and after-methionine load

RESUMO

INTRODUÇÃO: Metionina (Met), cisteína (Cys), homocisteína (Hcy) e taurina (Tau) são os qautro aminoácidos sulfurados (AAS), mas apenas a Met e Cys são incorporadas em proteínas. Os três principais produtos dos AAS, glutationa, (GSH), Hcy e Tau influenciam, principalmente, as respostas inflamatória e imune. A Tau e GSH melhoram a inflamação, enquanto que a Hcy apresenta efeito oposto. Os pacientes HIV+ apresentam baixos níveis de GSH e outros nutrientes antioxidantes, mostrando relação direta entre Cys (e GSH) com células CD4 +. Não se conhece o mecanismo pelo qual as mudanças na ingestão dos AAS influenciam este fenômeno e as relações entre Hcy, doenças inflamatórias e alterações in vitro no comportamento das células imunes criou nota cautelar sobre a suplementação de dietas com AAS. OBJETIVOS: investigar as vias dos AAS em pacientes HIV+ nas condições de jejum e pós-sobrecarga de Met frente à dieta habitual (DH) isolada ou acompanhada da suplementação de Cys (NAC) ou glutamina (GIn). MÉTODOS: 12 pacientes HIV+ (6 M e 6 F, de 25 a 36 anos), sob tratamento anti-retroviral pelo esquema tríplice, sem infecções secundárias e 20 controles saudáveis (10 M e 10 F, 23-28 anos) foram randomicamente distribuídos para suplementação com NAC (N-acetilcisteína, 1g/d ou GIn (20 g/d) em estudo cruzado com 7 dias de dieta separados por uma semana de washout (Wo com DH). Amostras de sangue após jejum noturno de 10 a 12 horas foram coletadas antes (MO) e após (M1) cada regime dietético. A seguir, os indivíduos ingeriram metionina (100 mg/kg) com coletas de sangue após 2 e 4 horas para a determinação da área abaixo da curva (AAC)...

ABSTRACT

Methionine (Met), cysteine (Cys), homocysteine (Hcy), and, taurine (Tau) are the 4 sulfur-containing amino acids (SAA), but only Met and Cys are incorporated into proteins. The 3 major products of SAA, glutathione (GSH), Hcy and Tau influence, mainly, inflammatory and of immune responses. Tau and GSH ameliorate inflammation whereas Hcy has the opposite effect. HIV+ patients present low levelis of GSH and other antioxidants nutrients, showing a direct relationship between Cys (and GSH) with CD4+/ cells. How changes in SAA intake influence this phenomenon is unknown and the relationships among Hcy, inflammatory diseases, and in vitro alterations in immune cell behavior create a cautionary note about supplementation of diets with SAA. OBJECTIVE: To investigate SAA pathways in HIV+ patients on fast and Met-overload (Met-DL) states after taken diet habitual without (HD) or with supplements of Cys (NAC) or glutamine (Gln). METHOOS 12 HIV+ (6M and 6F, 25-36 yrs old) patients under HAART without secondary infections and 20 healthy (10M and 10F, 23-28 yrs old) controls were randomly assigned to either NAC (N-acetylcysteine, 1g/d) or Gln (20g/d) diets, in a 7-day diet crossover design, separated by a 7-day washout (with HD) period. Blood samples were drawn after overnight fast before (MO) and after each dietary treatments (M1) for the resting measurements. Immediately after blood sampling ali subjects started the Met-DL by ingesting at once 100 mg Met/kg BW and having the blood draw after 2 and 4 hours for the area under the curve (AUC) determination. At MO both groups were assessed for anthropometry (BMI, kg/m2), glomerular (plasma urea and creatinina) and hepatocellular (plasma γGT activity) funetions, nutritional (albumin, calcium, folic acid and vitamin B12) and antioxidant (uric acid, GSH, GSSG, Hey) states, glucose, lipids (triglycerides and cholesterol fractions) and SAA, serine (Ser), glyeine (Gly), glutamate (Glu) and Gln. The HIV+ group was characterized also by viral load, CD4+ and CD8+ counts. The statistical comparisons between groups and among diets showed group homogeneity for 8MI, albumin, calcium, vitamin B12, Hey, HDL-cholesterol, urea and creatinine. The patients presented higher values of glucose, triglycerides, γ-GT, LDL-cholesterol, and GSSG along with lower concentrations of uric acid, GSH and all but Hcy amino acids. The Met-OL equalized (Δ values) the groups for Met, Hcy, Tau and Gln. NAC and Gln diets led the HIV+ group to a higher concentrations of GSH (NAC > Gln) by acting differently on its precursors Gly (Gln > NAC) and Cys (NAC > Gln), resulting similar consumption of Ser and production of Tau. Both diets reduced GSSG/GSH (NAC > Gln) and only NAC increased (6 x) Hey. The later was worsened by Met-OL. Thus HIV+ results in multiple deficiencies of vitamins and amino acids leading to lower levels of GSH and higher GSSG/GSH ration. The main problems of lower formation of Cys and low ineorporation of Cys and Gly into GSH were greatly solved by giving Met, NAC and Gln to the patients, hence remaining the drawback of increasing Hcy with Met or NAC supplements.