title: Glutathione supplementation improves macrophage functions in HIV.
abstract: In this study, we determined the effects of glutathione (GSH)-enhancing agents in restoring the levels of GSH in isolated macrophages from individuals with HIV infection thereby resulting in improved control of Mycobacterium tuberculosis. Our results indicate that treatment with N-acetyl cysteine or a liposomal formulation of glutathione (lGSH) resulted in replenishment of reduced also known as free GSH (rGSH), and correlated with a decrease in the intracellular growth of M. tuberculosis. Finally, we observed differences in the amount of the catalytic subunit of glutamine-cysteine ligase (GCLC), glutathione synthase, and glutathione reductase present in macrophages derived from healthy and HIV-infected individuals. These changes correlated with changes in free radicals as well as rGSH levels. Our results indicate that HIV infection leads to increased production of free radicals and decreased production of GCLC resulting in depletion of rGSH and this may lead, in part, to the loss of innate immune function observed in HIV patients. These findings represent a novel mechanism for control of M. tuberculosis infection, and a possible supplement to current HIV treatments.
authors: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA.
authors: Devin
authors: D
authors: Morris
authors: Carlos
authors: C
authors: Guerra
authors: Melissa
authors: M
authors: Khurasany
authors: Frederick
authors: F
authors: Guilford
authors: Beatrice
authors: B
authors: Saviola
authors: Ying
authors: Y
authors: Huang
authors: Vishwanath
authors: V
authors: Venketaraman
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage; D048708:Cell Growth Processes / Q000187:drug effects; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D019587:Dietary Supplements; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000008:administration & dosage*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007165:Immunosuppression Therapy; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*
chemical_list: D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D000111:Acetylcysteine