Allopurinol
Allopurinol plus standard resuscitation preserves hepatic blood flow and function following hemorrhagic shock.

Flynn WJ Jr, Hoover EL.

Department of Surgery, State University of New York at Buffalo 14215.

To determine the contribution of ischemia-reperfusion injury (IRI) to the blood flow deficit and hepatocellular dysfunction seen after resuscitation from hemorrhagic shock, the xanthine oxidase inhibitor allopurinol was given to rats as a 50 mg/kg bolus after shock but before resuscitation and continued as a 25 mg/kg/h infusion. Resuscitation with shed blood and lactated Ringer's restored cardiac output and blood pressure in both groups. Control animals demonstrated a reduction in total hepatic and effective hepatic blood flow to 59% and 43% of baseline values, respectively. Allopurinol resulted in a return to baseline values of both variables. Allopurinol treatment resulted in a 350% increase in xanthine, a 630% increase in hypoxanthine, and a 70% reduction in uric acid concentrations. These data suggest that IRI contributes to the organ dysfunction and blood flow deficits seen after resuscitated hemorrhagic shock the effect of which can be attenuated by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7996611&dopt=Abstract allopurinol Zyloprim



Allopurinol
The effect of allopurinol on Na+K+ATPase related lipid peroxidation in ischemic and reperfused rabbit kidney.

Aricioglu A, Aydin S, Turkozkan N, Durmus O.

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

1. Na+K+ATPase is a membrane bound enzyme whose activity is essential for maintenance of cell viability. Lipid peroxidation changes membrane fluidity and enzyme activity. 2. The purpose of this study was to investigate the effect of allopurinol (free radical scavenger) on Na+K+ATPase activity in rabbit kidney cortex membrane. In this in vivo study we created ischemia and reperfusion in rabbit kidneys. 3. Enzyme activity were low in ischemic and reperfused kidneys, compared to the controls. In allopurinol treated ischemic and reperfused groups, the levels of Na+K+ATPase activity were high compared to the untreated group. 4. It has been concluded that allopurinol may protect this enzyme activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8026734&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol, indomethacin and riboflavin enhance radiation lethality in mice.

Floersheim GL.

Department of Research, University Hospital, Basel, Switzerland.

Two widely used drugs, allopurinol and indomethacin, and the vitamin riboflavin increased the response of mice to ionizing radiation. In mice a dose of 10.5 Gy of gamma rays from a 60Co source resulted in a dose-dependent shortening of survival times after pretreatment with the three agents, applied at doses which were well tolerated alone. When the dose dependency of these drugs on the influence on survival was tested, two response patterns emerged. Indomethacin (25 mg/kg) shifted the survival curve to the left and reduced the LD50 from approximately 6.5 Gy to approximately 4.5 Gy. Allopurinol (100 mg/kg) diminished the survival rate to approximately 50% irrespective of the radiation dose (ranging from 0.75 to 6.0 Gy). A similar though less striking trend was seen with riboflavin (120 mg/kg), which reduced the survival rate to approximately 65% in the dose range from 3 to 6 Gy. Mortality in mice treated with allopurinol or riboflavin and irradiated with nonlethal exposures (from radiation alone) occurred within the first few days after irradiation, suggesting a different type of injury than is usually associated with radiation death. Although doses of the three drugs used clinically are clearly lower than those providing enhanced radioresponse in our experiments, subtle and nonovert injury caused by combined exposure to the drugs and radiation cannot be completely excluded.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8052701&dopt=Abstract allopurinol Zyloprim



Allopurinol
Biochemical modulation of intraperitoneal fluorouracil by allopurinol-the effect on an experimental adenocarcinoma in the liver.

Lindner P, Carlsson G, Gustavsson B, Holmberg SB, Naredi P, Peterson A, Hafstrom L.

Department of Surgery, Sahlgrenska Hospital, Goteborg, Sweden.

In a rat liver tumour system with a nitrosoguanidine-induced carcinoma and in an in vitro system with the same tumour, the effect of allopurinol on the toxicity and antitumour effect of 5-fluorouracil (5-FU) was explored. Two doses of 5-FU, 30 and 60 mg/kg b.w. intraperitoneally (i.p.), were tested with a large dose of allopurinol subcutaneously (s.c.( (300 mg) in rats. The drugs were given for three consecutive days. The lethal toxicity of 60 mg 5-FU i.p. could not be counteracted by allopurinol. Allopurinol and 30 mg 5-FU reduced the tumour growth rate more than 5-FU alone. The spleen was smaller, as a sign of increased toxicity, without allopurinol. The concentration of allopurinol and its metabolites in the general circulation was high. In vitro, there was no additive or specific effect of allopurinol. These results indicate some in vivo metabolic modulation of 5-FU efficacy by allopurinol if 5-FU is administered intraperitoneally and allopurinol systemically.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8074485&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol as a cardioprotectant during coronary artery bypass graft surgery.

Weimert NA, Tanke WF, Sims JJ.

School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705-2222, USA.

OBJECTIVE: To examine the role of allopurinol as a cardioprotectant during coronary artery bypass graft (CABG) surgery. DATA SOURCES: A search of MEDLINE (1966-October 2002) was performed using the following terms: allopurinol, xanthine oxidase, oxygen free radical, and coronary artery bypass. References evaluated were limited to English-language and human studies, yielding 41 citations, 13 of which were found suitable. The 5 largest studies are discussed. DATA SYNTHESIS: Multiple studies with various doses have evaluated the effects of allopurinol on outcomes in CABG patients. These studies found that allopurinol can reduce in hospital mortality, improve cardiac performance, reduce incidence of arrhythmias, reduce markers of ischemia and free-radical generation, and reduce the need for inotropic support. However, these findings were not consistent between all studies. CONCLUSIONS: Allopurinol may reduce the incidence of CABG complications. Although the optimal dose has not been determined, reviewed literature suggests that patients should receive at least 600 mg one day prior to surgery, as well as at least 600 mg on the day of surgery.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14565806&dopt=Abstract allopurinol Zyloprim



Allopurinol
Effect of superoxide dismutase and allopurinol on impulse noise-exposed guinea pigs--electrophysiological and biochemical study.

Cassandro E, Sequino L, Mondola P, Attanasio G, Barbara M, Filipo R.

Department of Experimental and Clinical Medicine, University of Reggio, Reggio, Italy.

OBJECTIVE: To investigate the protective effect of two anti-reactive oxygen species (ROS) substances, copper-zinc superoxide dismutase (CuZn-SOD) and allopurinol, in impulse noise-exposed guinea pigs. MATERIAL AND METHODS: Allopurinol or CuZn-SOD were administered intraperitoneally before exposure to 125 dB SPL noise centered at 2.0-3.0 kHz, with a repetition rate of 4/s, for 1.8 h. Hearing thresholds were tested by means of electrocochleography after implanting the animals with permanent electrodes. The presence of lipoperoxides in the guinea pig cochleae exposed to noise-induced oxidative stress was determined by means of the dosage of malondialdhyde, evaluated by measuring the content of thiobarbituric acid reactive substances in perilymph samples. RESULTS: Acoustic stress induced ROS formation and both allopurinol and CuZn-SOD exerted a protective effect on the cochlea. Comparison of compound action potential thresholds in different animal groups showed that the temporary threshold shift was significantly lower in treated animals than in those without pharmacological protection. CONCLUSION: The protective effect of the antioxidant agents demonstrates that, even at a high level of impulse noise exposure, a metabolic mechanism of cochlear damage may still play an important role in noise-exposed sensorineural hearing loss.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14575394&dopt=Abstract allopurinol Zyloprim