Drugs online research references
Biochim Biophys Acta. 1979 Sep 12;570(1):215-20.
Behavior of N-methylated allopurinols and related 4-thioxopyrazolo [3,4-d]pyrimidines towards bovine milk xanthine oxidase.
Bergmann F, Frank A, Govrin H.
1. All available N-mono- and N,N'-dimethylallopurinols and the corresponding 4-thioxo derivatives have been tested as substrates or inhibitors of bovine milk xanthine oxidase (xanthine: oxygen oxidoreductase, EC 1.2.3.2). 2. None of the compounds tested revealed any inhibitory activity towards the enzyme. 3. All compounds were resistant to enzymic oxidation, with the exception of 7-methylallopurinol and its 4-thioxo analog. Both these compounds were attacked at position 6. 7-Methylallopurinol was oxidised nearly ten times faster than the isomeric 3-methylhypoxanthine. 4. These observations can be explained by assuming that for attack at C-6, the enzyme must bind both to N-1 and N-2 in the pyrazole ring and causes tautomerisation, which places a double bond at position 5,6 in the pyrimidine ring. This activation process resembles the activation of hypoxanthine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=486504&dopt=Abstract
Anticancer Res. 1994 May-Jun;14(3A):847-52.
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 pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8074485&dopt=Abstract
Pancreas. 1993 Jul;8(4):465-70.
Xanthine oxidase-mediated intracellular oxidative stress in response to cerulein in rat pancreatic acinar cells.
Suzuki H, Suematsu M, Miura S, Asako H, Kurose I, Ishii H, Houzawa S, Tsuchiya M.
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Intralobular oxygen radical formation was examined in cerulein-stimulated rat pancreatic acinar cells by digital imaging microscopic fluorography using a hydroperoxide-sensitive fluorescent probe, dichlorofluorescin (DCFH) diacetate. The isolated pancreatic acinar cells loaded with DCFH diacetate were microscopically observed, and the dichlorofluorescein (DCF) fluorescence yielded by DCFH oxidation via hydroperoxides was digitally processed. Within the initial 20 min after the application of cerulein (10 microM), intracellular oxidative stress was observed as indicated by the increase in DCF fluorescence intensity and reached its maximum at 60 min. DCF fluorescence intensity was then gradually decreased until 80 min, followed by a marked increase in propidium iodide (PI) fluorescence, suggesting irreversible cell death. Allopurinol (1 microM), a xanthine oxidase inhibitor, significantly attenuated the early increase of DCF fluorescence intensity as well as the late cell damage. Treatment with hyperbaric oxygen (PO2 300 mm Hg) also significantly attenuated both the increase of DCF fluorescence and the number of PI-positive cells. The results suggest that xanthine oxidase-mediated oxygen radicals may play an important role in cerulein-induced intracellular oxidative stress in pancreatic acinar cells of rats.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8361967&dopt=Abstract
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