Abstract:
:There is a growing body of experimental and clinical evidence to suggest that oral or rectal administration of 5-ASA or 5-ASA conjugates is associated with significant adverse side effects including pancreatitis, hepatitis, and renal toxicity. The objective of this study was to assess the ability of 5-ASA to interact with low-molecular-weight iron to yield oxygen-derived free radicals and to determine whether these oxidants could damage model biological compounds. We found that 5-ASA was very effective at chelating ferric iron (Fe3+), and it rapidly reduced Fe3+ to the ferrous form (Fe2+). Addition of the 5-ASA/Fe2+ chelate to solutions containing polyunsaturated fatty acids or deoxyribose resulted in lipid peroxidation and oxidative carbohydrate degradation, respectively. These results are consistent with the formation of the highly reactive (and cytotoxic) hydroxyl radical. Formation of this free radical species was confirmed by the ability of hydroxyl radical scavengers (dimethyl sulfoxide, dimethyl thiourea) to inhibit the 5-ASA/Fe-mediated oxidative reactions. Maximum hydroxyl radical formation was achieved at a 5-ASA-to-Fe3+ ratio of 1.0 (20 microM 5-ASA and 20 microM Fe3+). Increasing this ratio significantly inhibited OH. formation with a concomitant reduction in lipid peroxidation and deoxyribose degradation. Finally, we demonstrated that 5-ASA promotes the reductive release of Fe3+ from ferritin. Data obtained in this study suggest that 5-ASA may, under certain conditions, promote the formation of potentially injurious free radical species. These oxidative reactions may contribute to some of the adverse side effects known to be associated with the newer preparations of 5-ASA.
journal_name
Dig Dis Scijournal_title
Digestive diseases and sciencesauthors
Grisham MB,Ware K,Marshall S,Yamada T,Sandhu ISdoi
10.1007/BF01296008subject
Has Abstractpub_date
1992-09-01 00:00:00pages
1383-9issue
9eissn
0163-2116issn
1573-2568journal_volume
37pub_type
杂志文章abstract::We retrospectively reviewed the role of ursodeoxycholic acid in infants having nonsurgical cholestasis attending the Hepatology Clinic, New Children Hospital, Cairo University, Egypt, from 1985 until 2005. Files of 496 infants with neonatal hepatitis and 97 with intrahepatic bile duct paucity were included; of them 24...
journal_title:Digestive diseases and sciences
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journal_title:Digestive diseases and sciences
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journal_title:Digestive diseases and sciences
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journal_title:Digestive diseases and sciences
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journal_title:Digestive diseases and sciences
pub_type: 杂志文章
doi:10.1007/BF01550977
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journal_title:Digestive diseases and sciences
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journal_title:Digestive diseases and sciences
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journal_title:Digestive diseases and sciences
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