Plasma homocysteine and thiol redox states in HIV+patients

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dc.contributor.authorBurini, Roberto Carlos [UNESP]
dc.contributor.authorMoreto, Fernando [UNESP]
dc.contributor.authorBorges-Santos, Maria Doroteia [UNESP]
dc.contributor.authorYu, Yong-Ming
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionHarvard Medical School
dc.date.accessioned2018-12-11T17:27:20Z
dc.date.available2018-12-11T17:27:20Z
dc.date.issued2014-01-01
dc.description.abstractHuman immunodeficiency virus (HIV) replication induces oxidative stress that is produced by the constituent proteins of the virus and is amplified by host-cell immunological defenses. In general, the disease progresses with increased oxidative stress, while the antioxidant defenses, although present, are insufficient for neutralizing the damaging effects of reactive oxygen species (ROS). Among the deficient antioxidant defenses are components of the thiol redox system, especially glutathione (GSH), the main intracellular constituent. The progression of HIV+ disease is associated with lower GSH and cysteine (Cys) levels. Cys and homocysteine (Hcy) are derived from methionine (Met) by trans-sulfuration and trans-methylation pathways, respectively, and Hcy is converted to Met through the remethylation pathway. Hyperhomocysteinemia (HHcy) in HIV+ patients has been correlated with B-vitamin deficiencies, antiretroviral therapies (ART), and HIV+ co-morbidities.In a group of HIV+ patients under stable ART, the plasma Hcy response to an oral Cys supplementation with N-acetylcysteine (NAC) and the plasma Hcy response to an oral methionine loading (MetLo) were studied, compared with a non-HIV infected control group (Co). Overweight and HHcy were more prevalent in the control group than the HIV+ group. The HIV+ group presented with lower levels of the sulfur amino acids, Met, Hcy and Cys, a similar remethylation ratio (Met/Hcy) and a lower trans-sulfuration ratio (Hcy/Cys), lower GSH concentrations, and lower antioxidant capacity ratio (GSH/GSSG), compared with controls. After MetLo, a decrease in remethylation was observed, because of the exogenous supply of Met and an increased trans-sulfuration ratio, compared to controls. The levels of sulfur amino acids, GSH, and the antioxidant capacity were lower in the HIV+ group, compared with controls. After dietary NAC, there was normalization of Met because of enhanced remethylation activity, trans-sulfuration was decreased, and even though GSH was increased, the antioxidant capacity continued below controls. The combination of both dietary NAC and MetLo reduced the Hcy levels, but the Met levels, the remethylation and trans-sulfuration pathways, and the antioxidant capacities were similar between the HIV+ and control groups, and GSH exceeded control values. Thus HHcy was absent in HIV+ patients, even after oral NAC. These unexpected results are attributed to the chronic stable ART status of the HIV+ group and the low prevalence of lipodystrophy, confounded by the higher HHcy status observed in controls.en
dc.description.affiliationCentre for Nutritional and Physical Exercise Metabolism Department of Public Health UNESP-Sao Paulo State University
dc.description.affiliationMassachusetts General Hospital Department of Surgery Harvard Medical School
dc.description.affiliationUnespCentre for Nutritional and Physical Exercise Metabolism Department of Public Health UNESP-Sao Paulo State University
dc.format.extent151-163
dc.identifier.citationHomocysteine: Biosynthesis and Health Implications, p. 151-163.
dc.identifier.scopus2-s2.0-84958883632
dc.identifier.urihttp://hdl.handle.net/11449/177828
dc.language.isoeng
dc.relation.ispartofHomocysteine: Biosynthesis and Health Implications
dc.rights.accessRightsAcesso restrito
dc.sourceScopus
dc.subjectGlutathione
dc.subjectHIV
dc.subjectHomocysteine
dc.subjectN-acetyl cysteine
dc.subjectThiol redox system
dc.titlePlasma homocysteine and thiol redox states in HIV+patientsen
dc.typeCapítulo de livro

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