Allopurinol
[Donor allopurinol treatment improves organ preservation of the kidney also when using UW solution]

[Article in German]

Marx A, Heberer M, Jorgensen J, Gurke L, Mihatsch M, Landmann J.

Departement Chirurgie, Universitat, Kantonsspital Basel.

Kidney function following hypothermic preservation with Eurocollins (EC) was previously shown to be improved by donor treatment with Allopurinol (AP) [1]. The University of Wisconsin organ preservation solution (UW), however, contains Allopurinol (1 mM). A syngeneic rat kidney transplant model was used to investigate concurrent Allopurinol donor-pretreatment (40 mg/kg b.w.). Kidney graft function resulted to be improved by AP pretreatment following organ preservation with both EC or UW as evidenced by significant reduction in serum creatinine values. On day two following transplantation the respective serum creatinine values (mumol/l) with and without AP-pretreatment were 424 +/- 39 and 662 +/- 25 for EC, and 259 +/- 48 and 387 +/- 48 for UW organ preservation. Furthermore survival- and histology-data were also superior for recipients of kidney grafts from AP-pretreated donors. We conclude that Allopurinol concentration in the UW solution might be to low or that adding AP into an organ storage solution is not the best application modality.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1644614&dopt=Abstract allopurinol Zyloprim



Allopurinol
Effects of allopurinol on ischemic experimental pancreatitis.

Cassone E, Maneschi EM, Faccas JG.

Department of Surgery, School of Medical Science, Universidad Nacional de Cuyo, Mendoza, Argentina.

The effect of allopurinol, a xanthine oxidase inhibitor, on canine experimental ischemic pancreatitis was studied. The animals were divided into nine groups: 1. Group 1. Control with pancreatic ischemia; 2. Group 2. Received allopurinol once, previous to ischemia; 3. Group 3. Received allopurinol once, immediately after ischemia; 4. Group 4. Received allopurinol immediately after ischemia and then daily; and 5. Groups 5, 6, and 7 were controls for the operation, allopurinol, and its vehicle, respectively; 6. Group 8 (pancreatic ischemia) and Group 9 (that received allopurinol after ischemia and daily) were also studied histologically. Serum amylase was determined in all animals. In Groups 1 and 5, following the ischemic period, hyperamylasemia developed and a peak was reached 24 h after ischemia. In Group 2, a significant decrease of amylase levels was found, compared to matched controls immediately after ischemia and then rose, reaching on the fifth day a peak that was less than the controls at 24 h. In Group 3, the serum amylase level increased immediately to values similar to controls; later, there was a drop to levels lower than those found in controls, followed by a peak on the fifth day. In Group 4, there was no significant elevation in the amylase values. Groups 6 and 7 showed no changes of amylasemia. In this experimental model, allopurinol blocked or ameliorated significantly cellular injury, as shown by a decrease of amylase levels in blood, and of histopathological changes, depending on dose and time of administration. These results offer the possibility of a prophylactic therapy for chronic relapsing and idiopathic pancreatitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1711087&dopt=Abstract allopurinol Zyloprim



Allopurinol
Heme oxygenase induction by CoCl2, Co-protoporphyrin IX, phenylhydrazine, and diamide: evidence for oxidative stress involvement.

Tomaro ML, Frydman J, Frydman RB.

Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Argentina.

The induction of heme oxygenase in rat liver by cobaltous chloride (CoCl2) and Co-protoporphyrin IX is entirely prevented by the administration of alpha-tocopherol and allopurinol. CoCl2 was converted in the liver into Co-protoporphyrin IX before it induced heme oxygenase activity. Actinomycin and cycloheximide affected to a similar degree the induction of heme oxygenase by both CoCl2 and Co-protoporphyrin IX. Administration of either CoCl2 or Co-protoporphyrin strongly decreased the intrahepatic GSH pool, a decrease which was completely prevented by the administration of either alpha-tocopherol or allopurinol. The latter compounds prevented heme oxygenase induction as well as the decrease in hepatic GSH when administered 2 h before, together with, or 2 h after CoCl2. However, when given 5 h after administration of CoCl2, alpha-tocopherol and allopurinol showed no preventive effect. Similar results were obtained when Co-protoporphyrin IX was used, with the difference that when alpha-tocopherol and allopurinol were given 2 h after administration of the inducer, they showed no protective effect. Phenylhydrazine and diamide also induced heme oxygenase activity in rat liver. This inductive effect was preceded by a decrease in the intrahepatic GSH pool, which took place several hours before induction of the oxygenase. Administration of alpha-tocopherol and allopurinol prevented induction of the oxygenase but had no effect on the decrease in GSH levels. These results suggest that the induction of heme oxygenase by phenylhydrazine and the diamide is preceded by an oxidative stress which very likely originates in the depletion of GSH. The induction of heme oxygenase by hemin was not prevented by administration of alpha-tocopherol or allopurinol. Coprotoporphyrin IX did not affect the pattern of the molecular forms of hepatic biliverdin reductase, at variance with CoCl2, which is known to convert molecular form 1 of the enzyme into molecular form 3.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1716866&dopt=Abstract allopurinol Zyloprim



Allopurinol
The effect of antioxidants on ozone-induced airway hyperresponsiveness in dogs.

Matsui S, Jones GL, Woolley MJ, Lane CG, Gontovnick LS, O'Byrne PM.

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

The role of oxygen radicals in causing ozone-induced airway hyperresponsiveness in dogs was examined by pretreating dogs with allopurinol and/or deferoxamine mesylate (desferal), which are inhibitors of oxygen radical generation, before ozone inhalation. Acetylcholine airway responsiveness was measured before and after either air or ozone inhalation (3 ppm for 20 min) on 5 experimental days separated by at least 2 wk. On each day, the dogs were pretreated intravenously with allopurinol (50 mg/kg) followed by inhaled desferal (1,000 mg inhalation) or with allopurinol followed by the diluent for desferal or with the diluent for allopurinol and desferal or with both diluents. The effect of ozone on acetylcholine airway responsiveness was expressed as the differences in the log-transformed preozone-postozone acetylcholine provocative concentrations. When dogs received both diluents or either treatment alone, ozone inhalation caused airway hyperresponsiveness. The mean log differences for the preozone-postozone acetylcholine provocative concentration were 0.804 (SEM, 0.17) for both diluents, 0.524 (SEM, 0.16) for allopurinol alone, and 0.407 (SEM, 0.22) for desferal alone. However, the combination of allopurinol and desferal significantly inhibited the development of ozone-induced airway hyperresponsiveness, the log difference being 0.195 (SEM, 0.11) (p less than 0.05), without inhibiting ozone-induced neutrophil influx into the airways. The results suggest that the production of oxygen radicals is important in the pathogenesis of ozone-induced airway hyperresponsiveness.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1741540&dopt=Abstract allopurinol Zyloprim



Allopurinol
Cytotoxicity of liver macrophages against liver tumours. Influence of betamethasone, indomethacin and allopurinol.

Holmberg SB, Lindner P, Naredi P, Hafstrom L.

Department of Surgery, Sahlgrenska Hospital, Goteborg University, Sweden.

Macrophage activation with zymosan has an inhibitory effect on tumour take and initial tumour growth in the rat liver. 91 rats with syngeneic transplanted hepatoma in the liver were treated with zymosan (46) or saline (45). Betamethasone (glucocorticoid), indomethacin (prostaglandin synthesis inhibitor), allopurinol (oxygen radical scavenger) or saline were administered concomitantly. Tumour take, tumour growth and relative spleen weight were used as in vivo parameters of liver macrophages cytotoxicity and general macrophage activation. Zymosan inhibition of tumour take was counteracted by betamethasone, indomethacin and allopurinol. Betamethasone increased the growth rate of the non-zymosan treated tumours during seven days. Indomethacin decreased the growth rate of the tumours in non-zymosan treated rats up to 14 days. Allopurinol significantly blocked the zymosan inhibition of tumour take and tumour growth after 7 and 14 days. Allopurinol blocked zymosan induced increased relative spleen weight. It is proposed that the liver macrophage cytotoxicity induced by zymosan is in part mediated via production of oxygen radicals.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1768054&dopt=Abstract allopurinol Zyloprim



Allopurinol
[The efficacy of the allopurinol treatment of patients with gouty nephropathy]

[Article in Russian]

Siniachenko OV, Diadyk AI, Nikolenko IuI, Antonov AA, Gusak IIa, Zhitomirskii MI.

The efficacy was studied of using allopurinol in 68 patients with primary podagra. The obtained results were compared with the treatment of 118 other patients who received similar treatment but without allopurinol (zanthinoxidase inhibitor). Allopurinol increased essentially the efficacy of therapeutic measures though positive dynamics concerning the renal process was achieved in 1/3 of patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1771852&dopt=Abstract allopurinol Zyloprim