Allopurinol
Attenuation of ischemia-reperfusion injury of the liver in dogs by cyclosporine. A comparative study with allopurinol and methylprednisolone.

Yamanoi A, Nagasue N, Kohno H, Chang YC, Hayashi T, Nakamura T.

Second Department of Surgery, Shimane Medical University, Japan.

The effects of pretreatment with cyclosporine, allopurinol, or methylprednisolone on ischemia-reperfusion injury of the liver were investigated. A total of 32 adult mongrel dogs that received one of the pretreatments were divided into four groups and were subjected to 90 min liver ischemia. Serum activities of aspartate aminotransferase (s-AST) and lactate dehydrogenase, (s-LDH) as well as animal survivals were used as indicators of liver injury. The elevation of both s-AST and s-LDH was significantly suppressed by pretreatment with cyclosporine as much as by allopurinol. However a significant improvement in animal survival was obtained only in the cyclosporine-pretreated group. Pretreatment with methylprednisolone did not affect either the activities of s-AST and s-LDH or animal survivals when compared with the control group. These data suggest that cyclosporine is a potent protector against ischemic liver injury--as effective as allopurinol or methylprednisolone. Although the precise mechanism of the effect of cyclosporine on liver ischemia still remains unknown, these observations may be of use in liver transplantation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1858150&dopt=Abstract allopurinol Zyloprim



Allopurinol
Effect of allopurinol on adriamycin-induced impairment of wound healing.

Johnson H Jr, Zelnick R, Davis E, Wise L.

Department of Surgery, Long Island Jewish Medical Center, New Hyde Park, NY 11042.

Use of antineoplastic drugs perioperatively requires an understanding of their potential effects on healing wounds. Adriamycin is an antineoplastic drug with a wide range of antitumor activity. Prior studies have demonstrated that adriamycin impairs skin wound healing but these studies have offered limited explanations for the mechanism of action of the drug vis a vis impairment of healing wounds. In this study we investigated the effect of a xanthine oxidase inhibitor, allopurinol, on adriamycin-induced tissue injury to determine the role oxyradicals might play in reducing wound-breaking strength. Sixty-four Buffalo rats were studied. Eight animals were used to establish drug tolerances. Fifty-six animals were divided into four experimental groups; saline control (2 mL IP), allopurinol control (4.3 mg/kg po), allopurinol-adriamycin (4.3 mg/kg po + 6 mg/kg IV, respectively), and adriamycin (6 mg/kg IV). Animals treated with adriamycin alone had significantly reduced weight at postoperative day (POD) 7 compared to control groups (p less than .025). Bowel-bursting strength (BBS) of the animals treated with adriamycin alone was also significantly decreased at POD 7, compared to controls (p less than .025), and by POD 14 the animals treated with adriamycin alone had a significantly decreased fascial tensile strength, compared to the saline control (p less than .05). At no point did the animals treated with both allopurinol and adriamycin show a significantly decreased weight, BBS, or fascial tensile strength compared to control animals. Allopurinol appeared to protect against adriamycin toxicity on healing wounds. These results suggest that xanthine oxidase and possibly superoxide radicals play an important role in mediating adriamycin toxicity on healing wounds.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1911578&dopt=Abstract allopurinol Zyloprim



Allopurinol
[Mechanisms of the effect of allopurinol on the metabolism of adenine nucleotides]

[Article in Slovak]

Pechan I, Cornak V, Rendekova V, Mrazova J, Zimmer HG.

Ustav kardiovaskularnych chorob, Bratislave.

The effect of repeated administration of allopurinol (50 mg.kg-1 48, 24, and 4 hours before analysis) on the activity of enzymes of degradation and resynthesis of adenine nucleotides was studied. The activity of xanthine dehydrogenase and xanthine oxidase was inhibited in the heart, liver and kidney and the activity of membrane-bound 5'-nucleotidase was particularly elevated in the heart and brain, suggesting that membrane transport processes may be affected. The increase in the activity of hypoxanthine guanine phosphoribosyl transferase in the liver is indicative of a potential mechanism of positive action of allopurinol upon restoring the purine nucleotide store. The authors present their hypothesis on the mechanism of allopurinol action upon the metabolism of adenine nucleotides. The suggested mechanisms might become operative in protecting tissues against ischemia and reperfusion induced damage.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1913198&dopt=Abstract allopurinol Zyloprim



Allopurinol
Use of polymerase chain reaction (PCR) and hybridization assays to detect Trypanosoma cruzi in chronic chagasic patients treated with itraconazole or allopurinol.

Zulantay I, Honores P, Solari A, Apt W, Ortiz S, Osuna A, Rojas A, Lopez B, Sanchez G.

Cellular and Molecular Biology Program, Biomedical Sciences Institute, Faculty of Medicine, University of Chile, Santiago, Chile. izulanta machi.med.uchile.cl

The presence of Trypanosoma cruzi in chronic chagasic patients with negative xenodiagnosis (XD) after 6 years following completion of therapy with either itraconazole or allopurinol was assessed by polymerase chain reaction (PCR) and hybridization assays. A 330-bp DNA fragment amplified from the hypervariable regions of T. cruzi kinetoplastid minicircles was hybridized with total 32P-labeled kinetoplast DNA as probes. PCR alone enabled the identification of T. cruzi nucleotide sequences in 40% of the patients treated with itraconazole and in 60% of patients treated with allopurinol. PCR used in combination with hybridization detected parasite DNA in 60% and 53% of XD negative individuals treated with itraconazole or allopurinol, respectively. These results show that PCR and hybridization are more sensitive than conventional parasitological techniques in diagnosing patients that have undergone chemotherapy with itraconazole or allopurinol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15062917&dopt=Abstract allopurinol Zyloprim



Allopurinol
The protective effects of allopurinol and superoxide dismutase-polyethylene glycol on ischemic and reperfusion-induced cochlear damage.

Seidman MD, Quirk WS, Nuttall AL, Schweitzer VG.

Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, Detroit, MI 48202.

The purpose of this study was to assess the protective effects of allopurinol, a blocker of free oxygen radical (FOR) formation, and superoxide dismutase-polyethylene glycol (SOD-PEG), a scavenger of FORs, on ischemic and reperfusion-induced cochlear damage. Fifteen Wistar Kyoto rats (WKY) were randomly assigned to three groups: (1) a control group (5 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion as documented by laser Doppler flowmetry; (2) a drug-treated group (5 animals) that received allopurinol before ischemia/reperfusion; and (3) a drug-treated group (5 animals) that received SOD-PEG before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) of the cochlea was abolished, and the cochlear microphonic (CM) was reduced after ischemia. In contrast, both allopurinol and SOD-PEG-treated animals showed post-reperfusion sensitivity in CAP and CM measures. We interpret these results to indicate that damage to the cochlear from ischemia and subsequent reperfusion can be attenuated by pretreatment with allopurinol or SOD-PEG. This provides indirect evidence that FORs may be partially responsible for cochlear damage resulting from ischemic conditions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1945435&dopt=Abstract allopurinol Zyloprim



Allopurinol
[Prophylactic effect of allopurinol mouthwash against stomatitis induced by the chemotherapy (PMUE regimen) for gastrointestinal malignancies]

[Article in Japanese]

Fujimura T, Shima Y, Sawasaki K, Haryo S, Fujita H, Anada E, Shiota S.

Dept. of Surgery, Takaoka City Hospital, Japan.

For prevention of the chemotherapy-induced stomatitis we administered allopurinol mouthwash to 15 out of 38 patients who underwent PMUE regimen. The severity of stomatitis was graded on five scales according to the criteria of Japan Society For Cancer Therapy. The incidence of stomatitis was defined as patients number with stomatitis above Grade 2/all patients number. Six of 23 patients which were not given allopurinol mouthwash (control group) developed stomatitis of Grade 1 (three patients), Grade 3 (two), or Grade 4 (one). Only one patient given allopurinol mouthwash (AMW group), however, suffered from Grade 1 stomatitis. The incidence of stomatitis was 13.0% for a control group and 0% for an AMW group. The average graded toxicity was 0.07 for the AMW group significantly lower than 0.57 for the control group. There was no significant difference between the two groups in other clinical adverse effects or abnormal laboratory data. These results suggested that allopurinol mouthwash regimen was well tolerated and effective for prevention of the chemotherapy induced stomatitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1952966&dopt=Abstract allopurinol Zyloprim