Allopurinol
Xanthine oxidase mediates cyclic flow variations in a canine model of coronary arterial thrombosis.

Kuwano K, Ikeda H, Oda T, Nakayama H, Koga Y, Toshima H, Imaizumi T.

Third Department of Internal Medicine, Kurume University School of Medicine, Japan.

We investigated the hypothesis that xanthine oxidase (XO) mediates platelet aggregation and cyclic flow variations (CFVs) in stenosed canine coronary arteries. CFVs were produced by an external constrictor placed at the site of the coronary artery with the injured endothelium. The severity of CFVs was evaluated by a pulsed Doppler flow probe. If CFVs developed, dogs intravenously received allopurinol, a specific XO inhibitor. The transcardiac gradient (difference between coronary vein and left atrium) of purine metabolites was determined during CFVs and after allopurinol administration. Allopurinol significantly reduced CFVs (from 8 +/- 1 to 1 +/- 1 cycles/h, P < 0.01, n = 14), whereas saline did not (from 8 +/- 1 to 7 +/- 1 cycles/h, n = 7). In seven dogs with CFVs, the transcardiac gradient of xanthine and uric acid concentrations significantly increased after the establishment of CFVs and significantly decreased after the administration of allopurinol. In vitro platelet studies showed that XO enhanced (from 30.9 +/- 2.0 to 47.6 +/- 1.5%, P < 0.0001, n = 10) and allopurinol inhibited ADP-induced platelet aggregation (from 48.3 +/- 1.3 to 24.8 +/- 1.5%, P < 0.0001, n = 10). Our results indicate that allopurinol inhibits platelet aggregation in vitro and provides a protection against CFVs in vivo. Thus XO may be an important mediator in this model.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8764249&dopt=Abstract allopurinol Zyloprim



Allopurinol
Facile and rapid high-performance liquid chromatography method for simultaneous determination of allopurinol and oxypurinol in human serum.

Tada H, Fujisaki A, Itoh K, Suzuki T.

Department of Pharmaceutical Science, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan.

OBJECTIVE: To develop a rapid and sensitive assay for the simultaneous determination of allopurinol and oxypurinol in serum. METHOD: High-performance liquid chromatography (HPLC) with UV-detection. Sample preparation consists of protein precipitation by an addition of trichloracetic acid. RESULTS: Percentage recovery and intra-assay coefficient of variation (CV%) for allopurinol were 97.4-101.3 and 0.66-5.13, respectively, in the concentration range 0.5-5.0 microg/mL. For oxypurinol, the percentage recovery and the intra-assay CV% were 93.2-98.1 and 0.88-5.62, respectively, in the concentration ranges 0.4-20 microg/mL. There was no interference of endogenous compounds in this assay. CONCLUSION: This method is useful for routine therapeutic drug monitoring of allopurinol in a clinical setting.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12795781&dopt=Abstract allopurinol Zyloprim



Allopurinol
Prophylactic action of allopurinol against chemotherapy-induced stomatitis--inhibition of superoxide dismutase and proteases.

Nakamura K, Natsugoe S, Kumanohoso T, Shinkawa T, Kariyazono H, Yamada K, Baba M, Yoshinaka H, Fukumoto T, Aikou T.

Department of Pharmacy, Kagoshima University School of Medicine, Japan.

The activities of superoxide dismutase (SOD) and several proteases were measured in kidney of mice treated with allopurinol in order to elucidate the mechanism of prophylactic action of allopurinol against chemotherapy-induced stomatitis. The following results were obtained. Following 3 day administration of allopurinol 20 mg/day per os (Group C), the concentrations of allopurinol and oxipurinol in the renal tissue were 203.9 +/- 52.1 and 1141.7 +/- 194.8 micrograms/g, respectively. The SOD activity was significantly lower in Group C than in the untreated control group (p < 0.01). The enzyme activities of papain and trypsin were suppressed in Group C. However, the other proteases tested were not affected by the administration of allopurinol, indicating only weak anti-protease action of allopurinol. These results suggest that allopurinol may be effective to prevent chemotherapy-associated stomatitis via both direct and indirect actions to oral mucosa, that include inhibitory actions on xanthine oxidase as well as protease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8791995&dopt=Abstract allopurinol Zyloprim



Allopurinol
Effects of EGF and allopurinol on prostaglandin and lipid peroxide levels in mucosa of stomach in restraint cold stress.

Aricioglu A, Oz E, Erbas D, Gokcora N.

Department of Biochemistry, Medical Faculty, Gazi University, Ankara, Turkey.

The cold and restraint gastric stress models were used in rats. Mucosal levels of prostaglandins, which have a protective effect on cells, and lipid peroxidation, a possible etiological factor in stress-induced gastric mucosal injuries, were investigated. Epidermal growth factor (EGF), which protects the gastric tissue from stress-induced lesions, and allopurinol, which inhibits xanthine oxidase, were given intraperitoneally. Both EGF and allopurinol decreased lipid peroxidation at the mucosal surface of the stomach. At the same time, allopurinol increased the serum gastrin levels and decreased the mucosal prostaglandin levels. It is concluded that EGF protects the gastric mucosal surface by way of increased tissue prostaglandin levels. EGF also decreased both serum gastrin and tissue malondialdehyde, an indicator of lipid peroxidation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8804126&dopt=Abstract allopurinol Zyloprim



Allopurinol
Repetitive brief ischemia: intermittent reperfusion during ischemia ameliorates the extent of injury in the perfused kidney.

Willgoss DA, Zhang B, Gobe GC, Kadkhodaee M, Endre ZH.

Department of Medicine, School of Medicine, University of Queensland, Royal Brisbane Hospital, Brisbane, Australia.

Acute renal failure commonly follows reduced renal perfusion or ischemia. Reperfusion is essential for recovery but can itself cause functional and structural injury to the kidney. The separate contributions of ischemia and of reperfusion were examined in the isolated perfused rat kidney. Three groups were studied: brief (5 min) ischemia, 20 min ischemia, and repetitive brief ischemia (4 periods of 5 min) with repetitive intervening reperfusion of 5 min. A control group had no intervention, the three ischemia groups were given a baseline perfusion of 30 min before intervention and all groups were perfused for a total of 80 min. In addition, the effects of exogenous *NO from sodium nitroprusside and xanthine oxidase inhibition by allopurinol were assessed in the repetitive brief ischemia-reperfusion model. Brief ischemia produced minimal morphological injury with near normal functional recovery. Repetitive brief ischemia-reperfusion caused less functional and morphological injury than an equivalent single period of ischemia (20 min) suggesting that intermittent reperfusion is less injurious than ischemia alone over the time course of study. Pretreatment with allopurinol improved renal function after repetitive brief ischemia-reperfusion compared with the allopurinol-untreated repetitive brief ischemia-reperfusion group. Similarly, sodium nitroprusside reduced renal vascular resistance but did not improve the glomerular filtration rate or sodium reabsorption in the repetitive brief ischemia-reperfusion model. Thus, these studies show that the duration of uninterrupted ischemia is more critical than reperfusion in determining the extent of renal ischemia-reperfusion injury and that allopurinol, in particular, counteracts the oxidative stress of reperfusion.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12803502&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol treatment results in elevated prostate-specific antigen levels in prostatic fluid and serum of patients with non-bacterial prostatitis.

Persson BE, Ronquist G.

Department of Urology, University Hospital, Uppsala, Sweden.

Non-bacterial prostatitis is a common problem in young men. It is a disease which is often recurrent and each episode lasts for several months. Different causative mechanisms of the disease have been discussed including identified and non-identified microorganisms, stone formation and psychological factors. It was shown in an earlier study that urinary reflux (as shown by a high creatinine concentration in prostatic fluid) took place to a varying extent in the prostatic ducts and this reflux was related to prostatic pain and urate concentration in expressed prostatic secretion (EPS). Allopurinol treatment lowered the urate concentration in EPS and relieved the subjective discomfort. This study reports serum (S) levels of prostate-specific antigen (PSA) in patients with non-bacterial prostatitis and the way in which S-PSA was affected by allopurinol treatment. It is also shown that the S-PSA level is age dependent. A correlation existed between the S-PSA concentration and EPS content of white blood cells. Patients with high EPS urate concentrations corresponded to low S-PSA levels and allopurinol treatment resulted in elevated S-PSA levels. PSA in EPS was also increased by allopurinol treatment. Hence, an increased release of PSA from the prostate gland was noted upon allopurinol treatment. The mechanism of the allopurinol-induced release is obscure. It might be explained by an induction of PSA synthesis via an allopurinol effect on the genome but an increased leakage of the prostatic cells elicited by allopurinol could no be ruled out.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8821701&dopt=Abstract allopurinol Zyloprim