Allopurinol
Effects of allopurinol and deferoxamine on reperfusion injury of the brain in newborn piglets after neonatal hypoxia-ischemia.

Peeters-Scholte C, Braun K, Koster J, Kops N, Blomgren K, Buonocore G, van Buul-Offers S, Hagberg H, Nicolay K, van Bel F, Groenendaal F.

Department of Neonatology, Image Sciences Institute, University Medical Center, 3584 EA Utrecht, The Netherlands.

The hypothesis was tested that treatment with allopurinol, a xanthine oxidase inhibitor, or deferoxamine, a chelator of nonprotein-bound iron, preserved cerebral energy metabolism, attenuated development of edema, and improved histologic outcome in the newborn piglet at 24 h after hypoxia-ischemia. Thirty-two newborn piglets were subjected to 1 h of hypoxia-ischemia by occluding both carotid arteries and reducing the fraction of inspired oxygen; five newborn piglets served as sham-operated controls. The depth of hypoxia-ischemia was controlled by phosphorous magnetic resonance spectroscopy. Upon reperfusion and reoxygenation, piglets received vehicle (n= 12), allopurinol (30 mg/kg/d, n = 10), or deferoxamine (12.5 mg/kg/d, n = 10). The cerebral energy status was determined with phosphorous magnetic resonance spectroscopy. The presence of vasogenic edema was assessed by T2-weighted magnetic resonance imaging. Brain cell injury was assessed with caspase-3 activity, histology, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end (TUNEL)-labeling. At 24 h after hypoxia-ischemia, the phosphocreatine/inorganic phosphate ratios were significantly decreased in vehicle-treated, but not in allopurinol- or deferoxamine-treated piglets. Water T2 values were significantly increased at 24 h after hypoxia-ischemia in cerebral cortex, thalamus, and striatum of vehicle-treated piglets, but not in allopurinol- and deferoxamine-treated piglets. No differences in caspase-3 activity, histologic outcome, or TUNEL-labeling were demonstrated between the three treatment groups. We suggest that allopurinol and deferoxamine may have an additional value in the treatment of perinatal hypoxia-ischemia with other neuroprotective agents or in combination with hypothermia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12815112&dopt=Abstract allopurinol Zyloprim



Allopurinol
The protective effect of allopurinol on cholestatic liver injury induced by bile duct ligation.

Mun KC, Kwak CS, Kwon KY.

Department of Biochemistry and Pathology, Keimyung University School of Medicine, Taegu, Korea.

To determine whether oxygen free radicals are responsible for the pathogenesis of the cholestasis induced by ligation of common bile duct (CBD) variables which reflect the hepatic function in the serum, the amount of superoxide radical production, and xanthine oxidase(XO) activity were studied. The activity of serum alanine aminotransferase, bilirubin level in the serum and the amount of superoxide radical production were lower in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Abnormalities of the microscopic structures were reduced in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Allopurinol, an inhibitor of XO, prevented the hepatic damage induced by CBD ligation through the inhibition of XO. These experiments demonstrate that oxygen free radicals are responsible for the pathogenesis of the cholestatic liver.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8843006&dopt=Abstract allopurinol Zyloprim



Allopurinol
Difference of the plasma concentration and urinary excretion of allopurinol, oxypurinol, and purine bases between dietary intake and fasting.

Yamamoto T, Moriwaki Y, Takahashi S, Tsutsumi Z, Yamakita J, Higashino K.

Third Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.

To investigate how much the metabolism of allopurinol, oxypurinol, and purine bases during dietary intake (total calorie 2,083 kcal, total protein 107.5 g, total lipid 74.1 g, total carbohydrate 228.3 g, total purine 180.5 mg) differs from that during fast, allopurinol (300 mg) was administered to 5 normal subjects after a 6-hour fast and then breakfast was taken. Four and 10 hours after the administration of allopurinol lunch and dinner were taken, respectively. Two weeks later the same protocol was performed, except for the intake of only water instead of diet. The fractional clearances and urinary excretions of oxypurinol, uric acid, and the clearance of creatinine were increased by dietary intake, compared with the respective ones resulting from fasting. At the same time the plasma concentrations of hypoxanthine, xanthine, and oxypurinol were decreased in dietary intake, compared with the respective ones in fasting, while the urinary excretion of neither allopurinol, hypoxanthine, nor xanthine was affected. These results suggest that the administration of allopurinol at bed time (during the nocturnal fast) may be more effective than that after breakfast in order to decrease the plasma concentration of uric acid.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8861734&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol reduces bacterial translocation, intestinal mucosal lipid peroxidation, and neutrophil-derived myeloperoxidase activity in chronic portal hypertensive and common bile duct-ligated growing rats.

Schimpl G, Pesendorfer P, Steinwender G, Feierl G, Ratschek M, Hollwarth ME.

Department of Pediatric Surgery, University of Graz, Medical School, Austria.

Bacterial translocation (BT) from the gastrointestinal tract has been thought to play a role in the pathogenesis of septic complications in patients with chronic portal hypertension (PH) and obstructive jaundice. The purpose of this study was to investigate the incidence of BT and to assess the role of intestinal mucosal malondialdehyde (MDA) levels as an indicator of lipid peroxidation and polymorphonuclear neutrophil-derived myeloperoxidase (MPO) in chronic portal hypertensive and common bile duct-ligated rats. Twenty male rats were subjected to sham laparotomy (SL), 20 rats to calibrated portal vein constriction (PH), 20 rats to common bile duct ligation (CBDL), and 10 rats served as a nonoperated control group (NOP). After 4 wk, 10 animals of each operated group received 50 mg/kg allopurinol intraperitoneally, at 24 h, and again 2 h prior to estimation of BT, intestinal mucosal MDA, and MPO activities. In the NOP and SL groups, BT to the mesenteric lymph nodes (MLN) and spleen was present. In PH and in CBDL rats, BT to liver, portal vein, peritoneum, and caval vein occurred. Allopurinol treatment attenuated the frequence of BT in PH and decreased BT in CBDL rats significantly (p < 0.05). Ileal mucosal MDA levels (nanomoles/g) in untreated rats increased from 45.1 +/- 7.9 in SL to 98.2 +/- 9.1 in PH and to 102.2 +/- 11 in CBDL rats (p < 0.01). In the allopurinol groups the increase of MDA to 49.1 +/- 1.3 in PH, and 66.2 +/- 2.2 in CBDL was significantly lower (p < 0.01). MPO activity (units/g) in the ileal mucosa increased in untreated rats from 319 +/- 129 after SL to 866 +/- 104 after PH and to 1016 +/- 104 after CBDL (p < 0.01). Allopurinol significantly attenuated MPO activity to 369 +/- 44 in PH, and to 372 +/- 60 in CBDL animals (p < 0.01). In PH and CBDL rats significant BT, intestinal mucosal lipid peroxidation, and polymorphonuclear neutrophil-derived MPO activity occurred. Allopurinol reduced BT and improved intestinal mucosal MDA and MPO activities, suggesting that there might be an association between BT and intestinal mucosal lipid peroxidation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8865279&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol and glutamine attenuate bacterial translocation in chronic portal hypertensive and common bile duct ligated growing rats.

Schimpl G, Pesendorfer P, Steinwender G, Feierl G, Ratschek M, Hollwarth ME.

Department of Paediatric Surgery, University of Graz, Austria.

BACKGROUND: Spontaneous bacterial infections and septicaemia result in morbidity and mortality in patients with portal hypertension and obstructive jaundice. AIM: The aim of this study in rats was to investigate the incidence of bacterial translocation in portal hypertension and obstructive jaundice, and to evaluate the effects of allopurinol and glutamine. METHODS: Rats were subjected to sham laparotomy (SL), portal hypertension (PH) by calibrated stenosis of the portal vein, and common bile duct ligation (CBDL). Animals of each group were either treated with allopurinol (50 mg/kg twice a week), glutamine (1 g/kg/d), and allopurinol and glutamine. RESULTS: After four weeks, significant bacterial translocation in the untreated PH and CBDL rats occurred. Intestinal mucosal malondialdehyde concentrations (MDA), as an indicator for lipid peroxidation, and myeloperoxidase activity (MPO) released from activated neutrophils were also significantly increased (p < 0.01). Allopurinol and glutamine in PH and CBDL rats improved bacterial translocation, and decreased MDA and MPO values (p < 0.01). CONCLUSION: In PH and CBDL rats significant bacterial translocation, ileal mucosal lipid peroxidation, and neutrophil derived MPO activity occurred. Allopurinol and glutamine significantly reduced bacterial translocation, as well as ileal mucosal MDA and MPO activities.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8881808&dopt=Abstract allopurinol Zyloprim



Allopurinol
The effect of allopurinol pretreatment on intestinal hypoperfusion encountered after correction of intestinal volvulus.

Akgur FM, Olguner M, Yenici O, Gokden M, Aktug T, Yilmaz M, Atac G.

Department of Pediatric Surgery, Dokuz Eylul University, Medical Faculty, Izmir, Turkey.

After reversal of blood flow following a prolonged period of ischemia, blood flow returns for a few seconds and is reduced afterward. This is called "no-reflow phenomenon." Antioxidants such as allopurinol have been shown to prevent the occurrence of this phenomenon in organs other than the intestine. An experimental study was conducted to investigate the effect of allopurinol pretreatment on intestinal blood flow after correction of intestinal volvulus in rabbits. In group 1, baseline intestinal blood flow (IBF) was evaluated using radiolabeled red blood cells. In group 2, 720 degrees intestinal volvulus was created and IBF was evaluated 6 hours later. In group 3, intestinal volvulus was created and devolvulus was performed 6 hours later. Intraperitoneal isotonic saline was injected 60 minutes before correction of the volvulus. IBF was evaluated after correction of the volvulus. Group 4 had the same procedures as group 3, but allopurinol (200 mg/kg) was injected in place of the isotonic saline. IBF stopped 6 hours after volvulus. Compared with the baseline group, IBF was significantly lower in the group with volvulus + devolvulus (P < .01). The IBF of the allopurinol-treated group was significantly higher than that of the isotonic saline group (P < .01) and it did not differ significantly from that of the baseline group. Histopathological examination showed that intestinal volvulus leads to histological injury. The histological injury was more pronounced in the devolvulus group and was less severe in the allopurinol group in comparison to the isotonic saline pretreatment group (P < .01). It is concluded that allopurinol pretreatment prevents the intestinal hypoperfusion (no-reflow phenomenon) and histological injury encountered after correction of intestinal volvulus of 6 hours' duration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8887084&dopt=Abstract allopurinol Zyloprim