Allopurinol
Effect of allopurinol on lipid peroxidation induced in corporeal tissue by veno-occlusive priapism in a rat model.

Evliyaoglu Y, Kayrin L, Kaya B.

Department of Urology, Adana Numune Hospital, Turkey.

OBJECTIVE: To investigate the role of allopurinol in the attenuation of ischaemia- and reperfusion-induced corporeal injury in a rat model of veno-occlusive priapism. MATERIALS AND METHODS: Placebo or allopurinol were given to eight groups of rats before priapism (ischaemia) was induced using a vacuum-constriction device for a duration of 6 or 12 h. Half of the groups of rats undergoing the same duration of priapism had 1 h of detumescence after the constriction band was removed (reperfusion). A ninth group was not treated and received no drug, serving as controls. Corporeal homogenates were then examined for malondialdehyde (MDA) accumulation, derived from lipid peroxidation, using a thiobarbituric acid assay. RESULTS: The accumulation of MDA was significantly higher in the groups treated with placebo and undergoing ischaemia/reperfusion compared with the control group (P < 0.001), but was not significantly different between the placebo-treated ischaemic and reperfused groups (P > 0.05). Rats undergoing 6 and 12 h of ischaemia and reperfusion, and receiving allopurinol had significantly less accumulation of MDA compared with those receiving placebo (P < 0.005). CONCLUSIONS: Lipid peroxidation, an indicator of injury induced by reactive oxygen metabolites, occurred in corporeal tissue during and after veno-occlusive priapism in this rat model; when assessed by lipid peroxidation, allopurinol appeared to protect rat corporeal tissue against this injury.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9313672&dopt=Abstract allopurinol Zyloprim



Allopurinol
Effects of allopurinol on striatal dopamine, ascorbate and uric acid during an acute morphine challenge: ex vivo and in vivo studies.

Enrico P, Esposito G, Mura MA, Migheli R, Serra PA, Desole MS, Miele E, De Natale G, Miele M.

Institute of Pharmacology, University of Sassari, Italy.

In the present study in vivo and ex vivo experiments were combined to evaluate the effects of allopurinol on the neurochemical changes induced by an acute morphine challenge (2 mg kg-1, s.c.). In samples from rat striatum, levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), ascorbate (AA), dehydroascorbate (DHAA), hypoxanthine, xanthine and uric acid (UA) were measured. Brain microdialysis experiments were carried out in freely moving rats. Striatal dialysate levels were assayed for DA, DOPAC + HVA, AA and UA using liquid chromatography followed by electrochemical detection. Morphine administration increased the striatal levels of DA metabolites, UA and DHAA and the extracellular concentrations of DA, DOPAC + HVA, UA and AA. Allopurinol (50 mg kg-1 by gavage), an inhibitor of xanthine oxidase which catalyses oxidation of xanthine to UA, decreased basal UA and AA concentrations and the morphine-induced increase in DA metabolites and AA oxidation. Since oxidation of DA and xanthines generates reactive oxygen species (ROS) and AA and UA are the main cellular antioxidants, these findings suggest that: (a) single morphine administration increases DA and xanthine oxidative metabolism with a consequent increase in ROS production, which may account for changes in concentrations of extracellular AA and tissue DHAA; (b) allopurinol decreases morphine-induced DA and xanthine oxidation; (c) UA and AA may act in concert to regulate levels of ROS in the brain.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9356212&dopt=Abstract allopurinol Zyloprim



Allopurinol
Oxygen free radicals impair wound healing in ischemic rat skin.

Senel O, Cetinkale O, Ozbay G, Ahcioglu F, Bulan R.

Department of Plastic & Reconstructive Surgery, Istanbul University, Cerrahpasa Medical Faculty, Turkey.

Oxygen free radicals are produced and play an important role in ischemic injury. We therefore wished to investigate the role of free radicals on ischemic skin wound healing. For this purpose, H-shaped flaps, where the test ischemic wound is the horizontal line in the H, were created on the dorsum of the rat. To inhibit the probable hazards of free radicals, allopurinol and superoxide dismutase (SOD) were given to the animals. Most of the studied wound-healing parameters were impaired in the ischemic group. In the allopurinol-treated group, breaking strength was increased by 52% by day 7 and by 109% by day 14 (p < 0.0002 and p < 0.001), and in the SOD-treated group the increase was 69% both by days 7 and 14 of healing when compared with the ischemic control group (p < 0.003 and p < 0.002). Hydroxyproline content was increased 75% with allopurinol and 113% with SOD in the wound by day 7 (p < 0.03 and p < 0.001 respectively). SOD treatment caused a significant decrease in wound edema by day 7 of healing (p < 0.05). Histopathological evaluation revealed that in the SOD- and allopurinol-treated groups, the amount of collagen and its organization were more prominent when compared with the ischemic controls. These results show that oxygen free radicals play an important role in the failure of ischemic wound healing, and antioxidants partly improve the healing in ischemic skin wounds.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9374149&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol reduced hepatic ischemia-reperfusion injury exacerbated by inhalation of high-concentration oxygen in rats.

Matsumoto F, Sakai H, Yamaguchi M, Nakano H, Matsumiya A, Kumada K, Yoshida K, Shimura H, Machida H, Takeuchi S, Sasaya S, Midorikawa T, Sanada Y.

Department of Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan.

Exposure to high-concentration oxygen (O2) increases lipid peroxidation of the cellular membrane, leading to tissue injury which may involve hepatic ischemia-reperfusion (I/R) injury. We examined the effects of inhaling high-concentration O2 on hepatic I/R injury with allopurinol, which is a xanthine oxidase inhibitor. Partial hepatic ischemia was performed in rats with or without allopurinol under 21 or 100% O2 inhalation. Levels of lipid peroxide, serum liver enzymes, and hepatocellular oxidative stress in the 100% O2 group were significantly higher than in the 21% O2. Administration of allopurinol significantly inhibited those changes in the 100% O2 group. Severe degeneration of mitochondria were noted in the 100% O2 group, but appeared to be reduced by allopurinol. Results suggest that inhalation of high-concentration O2 during liver surgery may increase lipid peroxidation and exacerbate hepatic I/R injury, but those changes may be prevented by allopurinol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9405965&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol protects enterocytes from hypoxia-induced apoptosis in vivo.

Albuquerque RG, Sanson AJ, Malangoni MA.

Department of Surgery, West Virginia University, Morgantown 26506, USA.

BACKGROUND: Reactive oxygen species can cause apoptosis and may be involved in hypoxic injury to the small bowel. Xanthine oxidase (XO) has been implicated in reactive oxygen species production. We hypothesized that administration of allopurinol would protect rat enterocytes from hypoxia-induced apoptosis. METHODS: Twenty-four Sprague-Dawley rats (weight, 250-300 g) were subjected to 30 minutes of hypoxia (10% Fio(2)), then killed immediately or allowed to recover for an hour in room air (21% Fio(2)). Intraperitoneal allopurinol (50 mg/kg) or an equivalent amount of 0.9% saline was administered 1 hour before hypoxia. Control rats were exposed to 21% Fio(2) under similar conditions. Proximal jejunum was harvested from all animals in both groups and stained to detect apoptotic cells using terminal deoxynucleotidyl transferase-mediated biotinylated deoxynucleotide end labeling. In addition, sections of proximal jejunum were removed and the mucosal membrane was removed and flash frozen in liquid nitrogen for DNA fragmentation gel. RESULTS: Intraperitoneal administration of allopurinol significantly reduced the percentage of apoptotic villi in the proximal jejunum compared with those animals receiving saline (11 +/- 7 vs. 25 +/- 12 in the hypoxia no recovery group, 41 +/- 14 vs. 67 +/- 8 in the hypoxia with recovery group, mean +/- SD, Mann-Whitney test, < 0.05). Intestinal XO activity was also significantly reduced in the animals receiving allopurinol compared with those receiving saline (6.8 +/- 3.12 vs. 19.1 +/- 4.56 mU/mL/g wet tissue in the hypoxia no recovery group, 0.86 +/- 0.33 vs. 11.5 +/- 7.13 mU/mL/g wet tissue in the hypoxia with recovery group, mean +/- SD, Mann-Whitney test, < 0.05). CONCLUSION: Inhibition of XO appears to protect rat enterocytes from hypoxia-induced apoptosis in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12352473&dopt=Abstract allopurinol Zyloprim



Allopurinol
Microsurgical evaluation of experimental pancreatitis after allopurinol: a secretory serological and morphological study.

Brunelli A.

Department of Geriatric Surgery, University of Ancona, Italy.

The purpose of the present work was to evaluate the efficacy of allopurinol in rat cerulein-induced acute pancreatitis, by studying amylase and lipase concentrations in bile-pancreatic juice and serum, blood leukocytes, and pancreatic histology. Supramaximal doses of cerulein, injected intraperitoneally twice with a 1-h interval (50 micrograms/kg), caused a reduction in juice amylase and lipase, high levels of the two enzymes in serum, leukocytosis, and severe histological damage to the pancreas, including the presence of diffuse cellular necrosis. These responses were not substantially altered by cotreatment with allopurinol (40 mg/kg i.p. twice with a 1-h interval) or by posttreatment with allopurinol (60 mg/kg i.p. 3 h after cerulein). In contrast, pretreatment with allopurinol (40 mg/kg allopurinol, 1 h, 20 mg/kg allopurinol + 50 micrograms/kg cerulein, 30 min, 40 mg/kg allopurinol, 30 min, 50 micrograms/kg cerulein) had a clear protective effect on pancreatic morphology and function, as shown by higher juice amylase and lipase values, lower serum amylase and lipase concentrations, and an almost normal histological picture of the pancreas. We concluded that allopurinol is effective in preventing the acute pancreatitis caused by administration of supramaximal doses of cerulein, by blocking the free radical generation in pancreatic tissue.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7545294&dopt=Abstract allopurinol Zyloprim