Parenteral glutamine protects hepatic function during bone marrow transplantation.
Hepatic veno-occlusive disease (VOD) of the liver is a common complication following high-dose cytotoxic therapy for bone marrow transplantation (BMT). The major pathological changes are seen in centrilobular (zone 3) hepatocytes and adjacent endothelium. Glutathione (GSH) becomes depleted following chemotherapy and experimental evidence suggests reduced levels predispose to centrilobular hepatocyte and endothelial cell injury. Animal studies have shown that glutamine infusions can maintain GSH levels and protect against free radical injury. We have prospectively studied the effect of glutamine supplementation during BMT. Thirty-four patients undergoing BMT were randomised to receive either glycl-L-glutamine (n = 18) or an isonitrogenous mixture of non-essential amino acids (n = 16). Glutamine was shown to significantly preserve protein C (days +4 and +7, P < 0.05) and albumin levels (days 0 and +4, P < 0.02). Markers of thrombin and plasmin generation (thrombin-antithrombin, prothrombin fragment F1+2 and plasmin-antiplasmin levels) were not significantly changed between the two groups. These findings suggest that glutamine preserves hepatic function but does not alter thrombin or plasmin generation during BMT. Previous studies have shown reductions in protein C, albumin, factor X and factor VII levels post BMT. Falling protein C levels have been shown to be predictive of severe VOD. These data suggest a role for glutamine in the protection of hepatic function following BMT.
Department of Haematology, University Hospital of Wales, Cardiff, UK.
S A
SA
Brown
A
A
Goringe
C
C
Fegan
S V
SV
Davies
J
J
Giddings
J A
JA
Whittaker
A K
AK
Burnett
C H
CH
Poynton
D000293:Adolescent; D000328:Adult; D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods* / Q000502:physiology; D004151:Dipeptides / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005341:Fibrinolysin / Q000096:biosynthesis; D005978:Glutathione / Q000378:metabolism; D006504:Hepatic Veno-Occlusive Disease / Q000517:prevention & control; D006801:Humans; D007263:Infusions, Parenteral; D007938:Leukemia / Q000628:therapy; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008223:Lymphoma / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D013917:Thrombin / Q000096:biosynthesis
D004151:Dipeptides; D011486:Protein C; D012709:Serum Albumin; C039788:glycylglutamine; D013917:Thrombin; D005341:Fibrinolysin; D005978:Glutathione