FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1973263780> ?p ?o ?g. }

• W1973263780 endingPage "168" @default.
• W1973263780 startingPage "159" @default.
• W1973263780 abstract "Summary. In order to define a predictive animal model for the effects of hydroxypyridinone (HPO) iron chelators in humans, we have compared the 28 d oral efficacy and toxicology of the HPO, 1,2-diethyI-3–hydroxypyridin-4–one (CP94) in rats and guinea-pigs and related the results to the contrasting metabolism of this compound in the two species. CP94 was highly effective at mobilizing liver iron in rats but showed toxicity at higher doses, whereas in the guinea-pig the compound lacked toxicity but was ineffective at mobilizing liver iron. These differences can be explained by the contrasting metabolism of the drug between the two species. In rats, at the top dose of 300 mg/kg intragastrically, all animals died before the end of the study, with no deaths or weight loss at lower doses. At 100 mg/kg, rat liver non-haem iron concentrations were reduced by 53% and 44% in females and males respectively (P<0.001). At this dose, adrenal medullary cell vacuolation, increased mammary secretory activity, vacuolation of corpora luteal cells and single cell hepatocyte necrosis were seen. There were no reductions in the white cell count. At 50 mg/kg rat liver non-haem iron concentrations were decreased by 50% and 34% in females and males respectively (P<0.02). In female rats this was associated with increased mammary secretory activity. In iron-overloaded rats given 100 mg/kg by gavage for 28 d, liver non-haem iron concentration was reduced by 39% (P<0.01) and serum ferritin by 71% (P<0.001). Ovarian and mammary changes were not influenced by iron loading. In guinea-pigs, CP94 was evaluated at 50 mg/kg, 100 mg/kg or 200 mg/kg by oral insufflation for 28 d. No reduction in liver iron was seen and no systematic dose related histological, biochemical or haematological effects were observed. Whereas in guinea-pigs 99% of urinary recovery following an oral dose of CP94 (100 mg/kg) was as the inactive glucuronide metabolite, in the rat only 23% of the dose was excreted in the urine as the glucuronide with remainder as the free drug or an iron binding metabolite. The lack of both efficacy and toxicity in the guinea-pig may therefore be explained by the rapid inactivation of CP94 by glucuronidation. This metabolism of CP94 in the guinea-pig is closer to humans than the rat, suggesting that both the efficacy and toxicity of this compound in humans may also be limited by glucuronidation." @default.
• W1973263780 created "2016-06-24" @default.
• W1973263780 creator A5001782654 @default.
• W1973263780 creator A5012933721 @default.
• W1973263780 creator A5020843793 @default.
• W1973263780 creator A5026022654 @default.
• W1973263780 creator A5029796279 @default.
• W1973263780 creator A5052881631 @default.
• W1973263780 creator A5074249169 @default.
• W1973263780 creator A5080010583 @default.
• W1973263780 creator A5085988087 @default.
• W1973263780 creator A5087105732 @default.
• W1973263780 creator A5091130564 @default.
• W1973263780 creator A5091386981 @default.
• W1973263780 date "1993-09-01" @default.
• W1973263780 modified "2023-10-03" @default.
• W1973263780 title "Contrasting interspecies efficacy and toxicology of 1, 2 -diethy 1–3 -hydroxypyridin-4-one, CP9 4, relates to differing metabolism of the iron chelating site" @default.
• W1973263780 cites W1604016987 @default.
• W1973263780 cites W1676024147 @default.
• W1973263780 cites W1948060141 @default.
• W1973263780 cites W1983683381 @default.
• W1973263780 cites W1988021435 @default.
• W1973263780 cites W1993488925 @default.
• W1973263780 cites W1998484700 @default.
• W1973263780 cites W2004227612 @default.
• W1973263780 cites W2010071741 @default.
• W1973263780 cites W2015337118 @default.
• W1973263780 cites W2020134645 @default.
• W1973263780 cites W2060033458 @default.
• W1973263780 cites W2066853173 @default.
• W1973263780 cites W2087254432 @default.
• W1973263780 cites W2092685230 @default.
• W1973263780 cites W2122752071 @default.
• W1973263780 cites W2269760103 @default.
• W1973263780 cites W2269916044 @default.
• W1973263780 cites W2312230130 @default.
• W1973263780 cites W2326684993 @default.
• W1973263780 cites W2411088972 @default.
• W1973263780 cites W293983036 @default.
• W1973263780 cites W30168135 @default.
• W1973263780 doi "https://doi.org/10.1111/j.1365-2141.1993.tb08660.x" @default.
• W1973263780 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8251385" @default.
• W1973263780 hasPublicationYear "1993" @default.
• W1973263780 type Work @default.
• W1973263780 sameAs 1973263780 @default.
• W1973263780 citedByCount "47" @default.
• W1973263780 countsByYear W19732637802012 @default.
• W1973263780 countsByYear W19732637802014 @default.
• W1973263780 countsByYear W19732637802016 @default.
• W1973263780 countsByYear W19732637802017 @default.
• W1973263780 countsByYear W19732637802019 @default.
• W1973263780 countsByYear W19732637802020 @default.
• W1973263780 countsByYear W19732637802021 @default.
• W1973263780 countsByYear W19732637802022 @default.
• W1973263780 countsByYear W19732637802023 @default.
• W1973263780 crossrefType "journal-article" @default.
• W1973263780 hasAuthorship W1973263780A5001782654 @default.
• W1973263780 hasAuthorship W1973263780A5012933721 @default.
• W1973263780 hasAuthorship W1973263780A5020843793 @default.
• W1973263780 hasAuthorship W1973263780A5026022654 @default.
• W1973263780 hasAuthorship W1973263780A5029796279 @default.
• W1973263780 hasAuthorship W1973263780A5052881631 @default.
• W1973263780 hasAuthorship W1973263780A5074249169 @default.
• W1973263780 hasAuthorship W1973263780A5080010583 @default.
• W1973263780 hasAuthorship W1973263780A5085988087 @default.
• W1973263780 hasAuthorship W1973263780A5087105732 @default.
• W1973263780 hasAuthorship W1973263780A5091130564 @default.
• W1973263780 hasAuthorship W1973263780A5091386981 @default.
• W1973263780 hasConcept C126322002 @default.
• W1973263780 hasConcept C134018914 @default.
• W1973263780 hasConcept C185592680 @default.
• W1973263780 hasConcept C202751555 @default.
• W1973263780 hasConcept C2776200302 @default.
• W1973263780 hasConcept C2778319317 @default.
• W1973263780 hasConcept C29730261 @default.
• W1973263780 hasConcept C42407357 @default.
• W1973263780 hasConcept C55493867 @default.
• W1973263780 hasConcept C62231903 @default.
• W1973263780 hasConcept C71924100 @default.
• W1973263780 hasConcept C86803240 @default.
• W1973263780 hasConcept C89311334 @default.
• W1973263780 hasConcept C98274493 @default.
• W1973263780 hasConceptScore W1973263780C126322002 @default.
• W1973263780 hasConceptScore W1973263780C134018914 @default.
• W1973263780 hasConceptScore W1973263780C185592680 @default.
• W1973263780 hasConceptScore W1973263780C202751555 @default.
• W1973263780 hasConceptScore W1973263780C2776200302 @default.
• W1973263780 hasConceptScore W1973263780C2778319317 @default.
• W1973263780 hasConceptScore W1973263780C29730261 @default.
• W1973263780 hasConceptScore W1973263780C42407357 @default.
• W1973263780 hasConceptScore W1973263780C55493867 @default.
• W1973263780 hasConceptScore W1973263780C62231903 @default.
• W1973263780 hasConceptScore W1973263780C71924100 @default.
• W1973263780 hasConceptScore W1973263780C86803240 @default.
• W1973263780 hasConceptScore W1973263780C89311334 @default.
• W1973263780 hasConceptScore W1973263780C98274493 @default.
• W1973263780 hasIssue "1" @default.
• W1973263780 hasLocation W19732637801 @default.

• next