Anti‐inflammatory effects of tetrahydrobiopterin on early rejection in renal allografts: modulation of inducible nitric oxide synthase

ABSTRACT Oxidative stress contributes to the development of early transplant failure. As nitric oxide synthases (NOS) can act as sources of superoxide, we investigated the effect of the NOS cofactor tetrahydrobiopterin (BH4) on oxyradical production and early rejection in a rat kidney transplantatio...

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Published in:The FASEB journal 2002-07, Vol.16 (9), p.1135-1137
Main Authors: Huisman, Albert, Vos, Ingrid, Faassen, Ernst E., Joles, Jaap A., Gröne, Hermann‐Josef, Martasek, Pavel, Zonneveld, Anton‐Jan, Vanin, Anatoly F., Rabelink, Ton J.
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - pharmacology
Anti-Inflammatory Agents - therapeutic use
Antioxidants - pharmacology
Antioxidants - therapeutic use
Biopterins - analogs & derivatives
Biopterins - pharmacology
Biopterins - therapeutic use
Cell Movement
Graft Rejection - drug therapy
Graft Rejection - enzymology
iNOS
Kidney - drug effects
Kidney - enzymology
Kidney - metabolism
Kidney Transplantation
Kinetics
Macrophages - drug effects
Macrophages - physiology
Models, Biological
Monocytes - drug effects
Monocytes - physiology
Nitric Oxide - biosynthesis
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
Pteridines - pharmacology
Pterins
Rats
Rats, Inbred Lew
renal transplantation
superoxide
Superoxides - metabolism
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Summary:ABSTRACT Oxidative stress contributes to the development of early transplant failure. As nitric oxide synthases (NOS) can act as sources of superoxide, we investigated the effect of the NOS cofactor tetrahydrobiopterin (BH4) on oxyradical production and early rejection in a rat kidney transplantation model. Allograft transplantation (Brown Norway to Lewis) showed more renal superoxide production and monocyte infiltration when compared with isografts (Lewis to Lewis). Administration of the stable BH4 precursor sepiapterin had no effect on superoxide production in the isografts (51±10 vs. 69±17 cps/10 mg protein), but led to a marked decrease in superoxide production in the allografts (116±11 vs. 60±6 cps/10 mg protein; P
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.01-0890fje