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 and have been implicated in the progression of neurologic damage and immune cell depletion caused by human immunodeficiency virus (HIV) infection. 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 with neurologic complications and 20 HIV-negative control patients undergoing lumbar punctures for other medical reasons. We confirmed recent studies of decreased CSF SAMe concentrations in HIV infection and demonstrated that diastereomers of SAMe are present in CSF but not in plasma or erythrocytes from both HIV-infected and HIV-negative patients. In HIV-infected patients, CSF GSH and cysteinyl-glycine, but not homocysteine or cysteine, were significantly reduced. This is the first report of decreased CSF GSH induced by HIV infection. GSH has a regulatory effect on the synthesis of SAMe in hepatic tissue, and the same mechanism may also apply in the CNS. Administration of SAMe-butanedisulphonate, 800 mg/d intravenously for 14 days, was associated with significant increases in CSF SAMe and GSH. These findings have potentially important therapeutic implications for the use of SAMe in protecting against SAMe and GSH deficiency in the CNS of HIV-infected patients.
Castagna
A
A
Department of Infectious Diseases, S. Raffaele Hospital, Milan, Italy.
Le Grazie
C
C
Accordini
A
A
Giulidori
P
P
Cavalli
G
G
Bottiglieri
T
T
Lazzarin
A
A
D000328:Adult; D005260:Female; D005978:Glutathione / Q000134:cerebrospinal fluid*; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D012436:S-Adenosylmethionine / Q000008:administration & dosage / Q000134:cerebrospinal fluid*
D012436:S-Adenosylmethionine; D005978:Glutathione