Xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) are single-gen
e products that exist in separate but interconvertible forms, XOD util
izes hypoxanthine or xanthine as a substrate and O-2 as a cofactor to
produce superoxide (. O-2(-)) and uric acid, XDH acts on these same su
bstrates but utilizes NAD as a cofactor to produce NADH instead of . O
-2(-) and uric acid, XOD has been proposed as a source of oxygen radic
als in polymorphonuclear, endothelial, epithelial, and connective tiss
ue cells, However, several questions remain about the physiological si
gnificance and functions of XOD on aging and oxidative stress, XOD is
reported to play an important role in cellular oxidative status, detox
ification of aldehydes, oxidative injury in ischemia-reperfusion, and
neutrophil mediation, For example, XOD may serve as a messenger or med
iator in the activation of neutrophil, T cell, cytokines, or transcrip
tion in defense mechanisms rather than as a free radical generator of
tissue damage, Emerging evidence on the synergistic interactions of .
O-2(-) a toxic product of XOD and nitric oxide, may be another illustr
ation of XOD involvement in tissue injury and cytotoxicity in an emerg
ent condition such as ischemia or inflammation.