CEREBROSPINAL-FLUID S-ADENOSYLMETHIONINE (SAME) AND GLUTATHIONE CONCENTRATIONS IN HIV-INFECTION - EFFECT OF PARENTERAL TREATMENT WITH SAME

The methylation and transsulfuration pathways are intimately linked an d have been implicated in the progression of neurologic damage and imm une cell depletion caused by human immunodeficiency virus (HIV) infect ion. We studied the following metabolites related to these pathways: S -adenosylmethionine (SAMe), homocysteine, cysteine, cysteinyl-glycine, and glutathione (GSH) in blood and CSF of 16 HIV-infected patients wi th neurologic complications and 20 HIV-negative control patients under going lumbar punctures for other medical reasons, We confirmed recent studies of decreased CSF SAMe concentrations in HIV infection and demo nstrated that diastereomers of SAMe are present in CSF but not in plas ma or erythrocytes from both HIV-infected and HIV-negative patients, I n HIV-infected patients, CSF GSH and cysteinyl-glycine, but not homocy steine or cysteine, were significantly reduced, This is the first repo rt of decreased CSF GSH induced by HIV infection. GSH has a regulatory effect on the synthesis of SAMe in hepatic tissue, and the same mecha nism may also apply in the CNS. Administration of SAMe-butanedisulphon ate, 800 mg/d intravenously for 14 days, was associated with significa nt increases in CSF SAMe and GSH. These findings have potentially impo rtant therapeutic implications for the use of SAMe in protecting again st SAMe and GSH deficiency in the CNS of HIV-infected patients.