Kidney xanthine effects

Pharmacokinetics Allopurinol is approximately 90% absorbed from the Gl tract. Effective xanthine oxidase inhibition is maintained over 24 hours with single daily doses. Allopurinol is cleared essentially by glomerular filtration oxipurinol is reabsorbed in the kidney tubules in a manner similar to the reabsorption of uric acid. 

Antitoxic effect. Sesame oil, adiministered to male Wistar rats, ameliorated hepatic and renal damage in a dose-dependent manner and increased survival in lipopolysaccha-ride-treated rats. It decreased lipid peroxide concentration in serum but not in liver and kidney. Serum nitrite production was unaffected by sesame oil ingestion, and the activity of xanthine oxidase was reduced in the lipopolysaccharide-challenged rats k Anti-tumor activity. Water extract of the dried seed, administered intragastrically to mice at a dose of 50 mg/animal daily for 5 days, was active on CA-Ehrlich-ascites, 18% increase in life-span. Intraperitoneal administration was active on Dalton s lyphoma and CA-Ehrlich-ascites, 19 and 39% increase in life-span, respectively ". Seed oil, administered to rats intraperito-neally with 1,2,5,6-dibenzanthracene or re-tene, was active on sarcoma ". 

Treatment the drug that most effectively inhibits the formation of uric acid is allopurinol, a competitive inhibitor of xanthine oxidase. Hypoxanthine and xanthine are excreted during allopurinol therapy. Allopurinol, as with guanine and hypoxanthine, can be converted to its ribonucleotide form by HGPRT. Reducing the formation of uric acid with allopurinol relieves the symptoms of gout and decreases the possibility that uric acid kidney stones will form. 

Clinical picture was consistent with tubular obstruction by U A and/or oxidized derivatives of adenine. Adenine is oxidized by xanthine oxidase to 2,8-dioxyadenine, a compound with a very low solubility and a definite toxic effect on kidney Therefore it is likely that dioxyadenine was the initiating factor... 

Allopurinol was given orally up to fifty times maximum human therapeutic doses without side effects. Allopurinol and oxipuri-nol appeared to be handled similarly by pig (798) and human kidney (in contrast to rat, mouse and dog) (9) Xanthine oxidase was maximally inhibited by allopurinol at 2.2 mmol (300 mg)/kg/day with no further increase in oxipurinol and xanthine excretion at higher doses. No limit, however, was found for the rmation of allopurinol riboside. 9k% of radioactivity om (6- C) allopurinol was recovered from the urine and no C incorporation was detected in tissue nucleotides. 

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