Effects of XO inhibitors in cerebral, intestinal, liver, kidney and lung ischemia-reperfusion injury
Model | Disease or Trigger | Mode of XO Inhibition | Effects of XO Inhibition | Reference |
|---|---|---|---|---|
| Cerebral I/R | ||||
| Gerbil | Temporary unilateral carotid artery occlusion | Tungsten, Allopurinol | Tungsten and allopurinol protected against neurological deficits and damage | Patt et al. (1988); Phillis and Lin (1991) |
| Gerbil | Global brain ischemia induced by the ligation of both common carotid arteries | Oxypurinol | Oxypurinol failed to protect against ischemic brain damage | Arai et al. (1998)* |
| Rat | Occlusion of bilateral common carotid arteries in SHRs | Allopurinol | Allopurinol pretreatment reduced infarct size and prevented mortality | Itoh et al. (1986) |
| Rat | Permanent middle cerebral artery occlusion | Allopurinol | Allopurinol pretreatment reduced infarct size | Martz et al. (1989) |
| Rat | Transient MCA occlusion | Oxypurinol | Oxypurinol reduced the ischemic cerebral damage, increased cellular ATP levels, and attenuated the neurological deficits | Lin and Phillis (1991, 1992); Phillis and Lin (1991); Phillis et al. (1995) |
| Rat | Transient MCA occlusion | Oxypurinol | Oxypurinol failed to show any preventive effect on the infarction in contrast to other free radical scavengers | Nakashima et al. (1999)* |
| Rat | Permanent MCA occlusion | Allopurinol | Only very high doses of allopurinol pretreatment reduced the infarct size, which was independent of XO inhibition | Lindsay et al. (1991) |
| Newborn rats and lambs | Ligation of the right common carotid artery | Allopurinol | Allopurinol reduced both cerebral edema and the extent of perinatal hypoxic-ischemic brain damage | Palmer et al. (1990, 1993); Shadid et al. (1998) |
| Rabbit | Focal cerebral ischemia | Allopurinol | Allopurinol pretreatment protected neural tissue in the early period after arterial occlusion and prevented cerebral injury in the late period and also decreased uric acid levels | Akdemir et al. (2001) |
| Human | Severely asphyxiated infants | Allopurinol | Allopurinol tended to improve survival and exerted beneficial effects on free radical formation, cerebral blood flow volume, and electrical brain activity | Van Bel et al. (1998) |
| Splanchnic I/R | ||||
| Mouse | Intestinal I/R | Allopurinol | Allopurinol reduced the colonic leukocyte infiltration, rolling and adhesion, levels of lipid peroxidation, and inflammatory chemokines | Riaz et al. (2002, 2003) |
| Rat | Intestinal ischemia or I/R | Allopurinol, tungsten | Allopurinol reduced I/R-induced neutrophil infiltration and bacterial translocation | Grisham et al. (1986); Deitsch et al. (1988); Vaughan et al. (1992) |
| Rat | Intestinal I/R | Allopurinol | Allopurinol decreased mucosal injury and reduced mortality | Megison et al. (1990) |
| Rat | Intestinal I/R | Allopurinol | Allopurinol-induced increased survival in intestinal ischemia in rats was attributed to an effect unrelated to XO inhibition | Garcia Garcia et al. (1990) |
| Rat | Intestinal I/R | Tungsten | Protection against gut reperfusion injury | Pitt et al. (1991) |
| Rat | Intestinal I/R | Allopurinol | Administration of allopurinol before reperfusion preserved intestinal motility | Hakguder et al. (2002) |
| Cat | Intestinal ischemia | Allopurinol | Allopurinol attenuated the necrosis of villus and crypt epithelium and the pathologically increased vascular permeability | Parks et al. (1982); Parks and Granger (1983); Granger et al. (1986); Nilsson et al. (1994); Kulah et al. (2004) |
| Dog | Intestinal I/R | Allopurinol | Allopurinol reduced histamine release in the reperfused gut | Boros et al. (1989) |
| Dog | Intestinal I/R | Allopurinol | Allopurinol significantly elevated the postischemic 6-keto prostaglandin 1α/thromboxane B2 ratio | Boros et al. (1991) |
| Liver I/R | ||||
| Mouse | Liver I/R | BOF-4272 | BOF-4272 attenuated hepatic damage indicated by decreased hepatic enzyme release and lipid peroxidation during hypoxia reoxygenation | Kakita et al. (2002) |
| Rat | Liver ischemia or I/R | NA | Up-regulation of XO, the conversion of XO to XDH during ischemia | Engerson et al. (1987); McKelvey et al. (1988); Frederiks and Bosch (1996) |
| Rat | Liver I/R | BOF-4272 | BOF-4272 reduced the release of chemoattractant in response to oxygen radicals reducible by Kupffer cells | Matsumura et al. (1998) |
| Rat | Liver I/R | Allopurinol | Allopurinol decreased I/R-induced lipid peroxidation and nuclear factor-κB activation | Matsui et al. (2000) |
| Rat | Liver I/R | Allopurinol | Allopurinol attenuated hepatic damage indicated by decreased hepatic enzyme release | Yildirim et al. (2002) |
| Kidney I/R | ||||
| Rat, rat kidney | Renal I/R | Allopurinol | Allopurinol improved morphology and renal function | Linas et al. (1990); Hestin and Johns (1999); Rhoden et al. (2000b) |
| Rat kidney | Repetitive renal I/R | Allopurinol | Allopurinol improved renal function after repetitive brief I/R in the isolated perfused rat kidney | Willgoss et al. (2003) |
| Dog | Renal I/R induced by transplantation | Allopurinol | Protection against kidney transplantation damage | Owens et al. (1974) |
| Lung I/R | ||||
| Rat lung | Lung I/R | Lodoxamide, allopurinol | Lodoxamide (1 mM) caused significant attenuation of postischemic lung injury in isolated rat lung model | Lynch et al. (1988); Okuda et al. (1993) |
| Rabbit lung | Lung I/R | Allopurinol | Allopurinol attenuated lung injury | Aiba et al. (1992) |
I/R, ischemia-reperfusion; MCA, middle cerebral artery.
↵* Studies concluded with negative results