Orally Active Multi-Functional Antioxidants Delay Cataract Formation in Streptozotocin (Type 1) Diabetic and Gamma-Irradiated Rats 英文参考文献.docVIP

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Orally Active Multi-Functional Antioxidants Delay Cataract Formation in Streptozotocin (Type 1) Diabetic and Gamma-Irradiated Rats 英文参考文献.doc

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Orally Active Multi-Functional Antioxidants Delay Cataract Formation in Streptozotocin (Type 1) Diabetic and Gamma-Irradiated Rats 英文参考文献

OrallyActiveMulti-FunctionalAntioxidantsDelay CataractFormationinStreptozotocin(Type1)Diabetic andGamma-IrradiatedRats JamesRandazzo1,PengZhang1,JunMakita1,KarenBlessing1,PeterF.Kador 1,2 ¤ * 1DepartmentofPharmaceuticalSciences,UniversityofNebraskaMedicalCenter,Omaha,Nebraska,UnitedStatesofAmerica,2DepartmentofOphthalmology,University ofNebraskaMedicalCenter,Omaha,Nebraska,UnitedStatesofAmerica Abstract Background:Age-relatedcataractisaworldwidehealthcareproblemwhoseprogressionhasbeenlinkedtooxidativestress and the accumulation of redox-active metals. Since there is no specific animal model for human age-related cataract, multipleanimalmodelsmustbeusedtoevaluatepotentialtherapiesthatmaydelayand/orpreventcataractformation. Methods/Principal Findings: Proof of concept studies were conducted to evaluate 4-(5-hydroxypyrimidin-2-yl)-N,N- dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 4) and 4-(5-hydroxy-4,6-dimethoxypyrimidin-2-yl)-N,N-dimethyl- 3,5-dioxopiperazine-1-sulfonamide (compound 8), multi-functional antioxidants that can independently chelate redox metalsandquenchfreeradicals,ontheirabilitytodelaytheprogressionofdiabetic‘‘sugar’’cataractsandgammaradiation- inducedcataracts.Priorto15Gyofwholeheadirradiation,selectgroupsofLongEvansratsreceivedeitherdietcontaining compound4or8,orasinglei.p.injectionofpanthethine,aradioprotectiveagent.Comparedtountreated,irradiatedrats, treatment with pantethine, 4 and 8 delayed initial lens changes by 4, 47, and 38 days, respectively, and the average formation of posterior subcapsular opacities by 23, 53 and 58 days, respectively. In the second study, select groups of diabeticSpragueDawleyratswereadministeredchowcontainingcompounds4,8orthealdosereductaseinhibitorAL1576. Asanticipated,treatmentwithAL1576preventedcataractbyinhibitingsorbitolformationinthelens.However,compared tountreatedrats,compounds4and8delayedvacuoleformationby20daysand12days,respectively,andcorticalcataract formationby8and3days,respectively,withoutreduci