Tetrahydrobiopterin attenuates ischemia-reperfusion injury following organ transplantation by targeting the nitric oxide synthase: investigations in an animal model

Abstract

Ischemia-reperfusion injury is a primarily non-allospecific event leading to the depletion of the essential nitric oxide synthase cofactor and potent antioxidant tetrahydrobiopterin. Suboptimal concentrations of tetrahydrobiopterin result in a reduced biosynthesis of nitric oxide leading to vascular endothelial dysfunction. Tetrahydrobiopterin supplementation has been shown to protect from this pathological state in a plethora of cardiovascular diseases including transplant-related ischemia-reperfusion injury. Even though still controversially discussed, there is increasing evidence emerging from both human as well as animal studies that tetrahydrobiopterin-mediated actions rely on its nitric oxide synthase cofactor activity rather than on its antioxidative properties. Herein, we review the current literature regarding the role of tetrahydrobiopterin in ischemia-reperfusion injury including our experience acquired in a murine pancreas transplantation model.

Keywords

• animal model
• ischemia-reperfusion injury
• nitric oxide
• organ transplantation
• tetrahydrobiopterin
• enzymes: calpain (ec 3.4.22.52); catalase (ec 1.11.1.6); glutathione peroxidase (ec 1.11.1.9); nadph oxidase (ec 1.6.3.1); nitric oxide reductase (ec 1.7.99.7); nitric oxide synthase (ec 1.14.13.39); phospholipase a2; (ec 3.1.1.4); superoxide dismutase (ec 1.15.1.1); xanthine oxidase (ec 1.17.3.2).