Allopurinol
Existence and participation of xanthine oxidase in reperfusion injury of ischemic rabbit myocardium.

Terada LS, Rubinstein JD, Lesnefsky EJ, Horwitz LD, Leff JA, Repine JE.

Webb-Waring Lung Institute, Denver, Colorado.

Using a highly specific assay that minimizes enzyme inactivation in vitro, we found that rabbit myocardial tissue contained low levels of xanthine oxidase (XO) and xanthine dehydrogenase (XD) activity that were effectively inhibited by pretreatment of hearts with allopurinol. In parallel, allopurinol treatment also improved ventricular developed pressure, peak systolic pressure, and coronary flow in isolated hearts subjected to 30 min of normothermic global ischemia and 30 min of reperfusion. Although function was protected by allopurinol treatment, creatine kinase (CK) release was not altered by allopurinol. Inhibition of myocardial XO with allopurinol did not increase myocardial ATP or phosphocreatine. In addition, allopurinol did not scavenge superoxide anion or hydrogen peroxide in vitro. The results support the possibility that relatively low amounts of XO activity, similar to levels reported in human myocardium, may contribute to cardiac ischemia-reperfusion injury.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2000975&dopt=Abstract allopurinol Zyloprim



Allopurinol
Development of patient-friendly preparations: preparation of a new allopurinol mouthwash containing polyethylene(oxide) and carrageenan.

Hanawa T, Masuda N, Mohri K, Kawata K, Suzuki M, Nakajima S.

Department of Pharmacy, Yamanashi Medical University, Tamaho, Yamanashi, Japan. thana res.yamanashi-med.ac.jp

Stomatitis is a harmful side effect induced by high and/or multiple dosing of cytotoxic drugs such as 5-fluorouracil. Allopurinol mouthwash has been used to prevent stomatitis induced by cancer chemotherapy. In the present study, the pharmaceutical utility of allopurinol mouthwash (Alkox-mw), which consists of polyethylene(oxide) (Alkox) and iota-carrageenan (INA), was investigated as a possible material for a new oral dosage preparation for improving the adhesiveness onto the oral mucosa. From the observation of the gel formation, which was studied as a function of the variety of the added Alkox and/or INA, the preferential compositions of Alkox-mw (Alkox:INA % ratio) seemed to be 1.0:(0-1.0) and (0-3.0):0.4, respectively. The adhesiveness and the spinnability of various allopurinol mouthwashes were also investigated using a creep meter. The adhesiveness of Alkox-mw increased with the increase in the amount of added Alkox. Furthermore, the adhesion force of Alkox-mw was greater than that of allopurinol mouthwash consisting of sodium carboxymethylcellulose (CMC-Na). From the in vitro assessment of mimicking the effusion of the allopurinol mouthwashes from the surface of the oral mucosa, the effusion of Alkox-mws was retarded by the added Alkox. The results obtained in the present study suggest that Alkox-mws may be useful as a new dosage form that adheres to the oral mucosa.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15089049&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol--a free radical scavenger--reduces reperfusion injury in skeletal muscle.

Oredsson S, Plate G, Qvarfordt P.

Department of Surgery, Helsingborg Hospital, Sweden.

Reperfusion of ischaemic skeletal muscle may lead to increased vascular permeability, oedema and ultimately muscle necrosis. Oxygen-derived free radicals have been suggested as aetiological factors in reperfusion injury. Amputated rabbit hindlimbs were subjected to 4 h of ischaemia followed by 2 h or reperfusion with Krebs' buffer. One limb from each animal was reperfused with oxygen-saturated buffer (reoxygenated limb) while the other limb was reperfused with nitrogen-saturated buffer (non-reoxygenated limb). Six animals received allopurinol orally 2 days prior to the experiment and ten animals received no treatment. The energy charge dropped from 0.90 to 0.54 during ischaemia and increased to 0.82 after reperfusion with oxygenated perfusate. Oedema was determined by limb weight and water content in muscle biopsies and muscle injury was assessed by uptake of [Tc99]methylenediphosphonate ([Tc99]MDP). The results were expressed in ratios, between the reoxygenated and nonreoxygenated limb. Without allopurinol treatment, the increase in water content and limb weight in reoxygenated limbs exceeded (p less than 0.05) non-reoxygenated limbs (ratios = 1.73 and 1.89, respectively). Allopurinol treatment significantly reduced (p less than 0.05 and p less than 0.02, respectively) the increase in water content and limb weight (ratios = 0.54 and 1.01, respectively). Without treatment, [Tc99]MDP-uptake was greater (p less than 0.05) in reoxygenated limbs than in non-reoxygenated limbs (ratio = 1.60). Allopurinol treatment significantly reduced (p less than 0.002) [Tc99]MDP-uptake in reoxygenated limbs (ratio = 0.80). These results demonstrate that additional injury to ischaemic skeletal muscle occurs during reperfusion with oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2009984&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol pretreatment improves evoked response recovery following global cerebral ischemia in dogs.

Mink RB, Dutka AJ, Hallenbeck JM.

Diving Medicine Department, Naval Medical Research Institute, Bethesda, Md 20814-5055.

The reperfusion of previously ischemic tissue may lead to the formation of highly reactive free radicals that promote tissue injury. Xanthine oxidase has been implicated as one source of these free radicals. We examined the role of xanthine oxidase in brain injury using a cerebrospinal fluid compression model of global cerebral ischemia with 15 minutes of ischemia and 4 hours of reperfusion. Seven dogs were pretreated with the xanthine oxidase inhibitor allopurinol (50 mg/kg for 5 days). Neurophysiological recovery was monitored with cortical somatosensory evoked potentials. As an attempt to correlate brain recovery with the mechanism of protection, free brain malondialdehyde was measured at the end of reperfusion by high-performance liquid chromatography. Brain water content was measured by wet-dry weights. Compared with seven untreated control dogs, allopurinol pretreatment significantly improved recovery of somatosensory evoked potentials after 4 hours of reperfusion. However, the amount of free malondialdehyde in the allopurinol-treated dogs was 32% greater than that in the controls. Brain water content was similar in the two groups. These results suggest that xanthine oxidase contributes to brain injury after ischemia and reperfusion. However, tissue damage caused by xanthine oxidase may be mediated through mechanisms other than free radical production.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2028498&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol-induced effects in premature baboons with respiratory distress syndrome.

Jenkinson SG, Roberts RJ, DeLemos RA, Lawrence RA, Coalson JJ, King RJ, Null DM Jr, Gerstmann DR.

Department of Medicine, University of Texas Health Science Center, Audie L. Murphy Veterans Administration Hospital, San Antonio, Texas.

To test the hypothesis that administration of allopurinol could modify the response to prolonged hyperoxia in premature baboons (140 days gestation) with respiratory distress syndrome, we evaluated physiological, pathological, and lung biochemical parameters in groups of premature baboons treated with mechanical ventilation and exposed to various amounts of oxygen for 6 days. Three groups of experimental animals were studied, including animals that received oxygen as needed to maintain arterial oxygen between 60 and 80 Torr [inspiratory O2 concentration- (FIO2) PRN], animals that received 100% oxygen continuously but also received allopurinol intravenously at a dose of 10 mg.kg-1.day-1 (FIO2-1.0 + allopurinol), and animals that received 100% oxygen continuously and the vehicle for allopurinol administration (FIO2-1.0). Pathological examinations of the experimental animals showed evidence of lung injury in both 100% oxygen-exposed groups, but the allopurinol-treated animals had findings more compatible with the FIO2-PRN group, with relatively few macrophages or polymorphonuclear lymphocytes being present in lung tissue. Lungs of animals treated with allopurinol were also more distensible and had a trend toward decreased lung water compared with the FIO2-1.0 group. Allopurinol-treated animals were able to induce lung glutathione concentrations and glutathione-related and antioxidant enzyme activities compared with the normoxic control (FIO2-PRN) group. Ventilator pressure requirements were also decreased in the allopurinol-treated animals compared with the FIO2-1.0 controls after 42 h. These data suggest that treatment of hyperoxia-exposed premature baboons with allopurinol for the first 6 days of life results in significant changes in lung responses and antioxidant defenses compared with vehicle-treated baboons exposed to 100% oxygen for the same time period.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2032982&dopt=Abstract allopurinol Zyloprim



Allopurinol
Oleic acid-induced injuries in the guinea-pig. Effects of allopurinol on cell dynamics, erythrocyte-catalase and uric acid plasma levels.

Hultkvist-Bengtsson U, Martensson L.

Department of Zoophysiology, University of Lund, Sweden.

1. Oleic acid was used to produce adult respiratory distress syndrome-like pulmonary microvascular injuries. The resulting injuries have previously indicated involvement of accumulating neutrophils (Hultkvist et al. 1988). Activated neutrophils release oxygen free radicals that may be possible to detect in the plasma. 2. The dynamics of neutrophils and platelets were studied in the guinea-pig after oleic acid-induced injury (0.03 ml/kg per 10 min). 3. As an indication of oxygen free radical activity, plasma levels of uric acid and red blood cell (RBC)-catalase, were analysed. 4. Allopurinol (10 mg/kg, i.p.) was given prior to oleic acid infusion to block the production of uric acid. 5. The neutropenia, in contrast to the thrombocytopenia seen at 15 min, was significantly inhibited in the allopurinol pretreated group compared with oleic acid and vehicle alone. 6. The blood plasma concentration of uric acid was significantly elevated after 15 min from start of experiment. Allopurinol pretreatment significantly reduced the uric acid plasma level. 7. The RBC catalase activity did not change with time within or between any groups. 8. The results indicate that sequestration of activated neutrophils in the microvasculature are to some extent oxygen free radical dependent.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2054954&dopt=Abstract allopurinol Zyloprim