Evaluation of Nephroprotective and Immunomodulatory Activities of Antioxidants in Combination with Cisplatin against Murine Visceral Leishmaniasis 英文参考文献.docVIP

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Evaluation of Nephroprotective and Immunomodulatory Activities of Antioxidants in Combination with Cisplatin against Murine Visceral Leishmaniasis 英文参考文献.doc

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Evaluation of Nephroprotective and Immunomodulatory Activities of Antioxidants in Combination with Cisplatin against Murine Visceral Leishmaniasis 英文参考文献

EvaluationofNephroprotectiveandImmunomodulatory ActivitiesofAntioxidantsinCombinationwithCisplatin againstMurineVisceralLeishmaniasis MeenakshiSharma1,RakeshSehgal2,SukhbirKaur1* 1Department ofZoology,Panjab University, Chandigarh,India, 2Department ofParasitology,PostgraduateInstitute ofMedicalEducation andResearch,Chandigarh, India Abstract Background: Most available drugs against visceral leishmaniasis are toxic, and growing limitations in available chemotherapeuticstrategiesduetoemergingresistantstrainsandlackofaneffectivevaccineagainstvisceralleishmaniasis deepensthecrisis.Antineoplasticdrugslikemiltefosinehaveinthepastbeeneffectiveagainsttheparasiticinfections.An antineoplasticdrug,cisplatin(cis-diamminedichloroplatinumII;CDDP),isrecognizedasaDNA-damagingdrugwhichalso inducesalterationofcell-cycleinbothpromastigotesandamastigotesleadingtocelldeath.Firstinvivoreportsfromour laboratoryrevealedtheleishmanicidalpotentialofcisplatin.However,highdosesofcisplatinproduceimpairmentofkidney, whichcanbereducedbytheadministrationofantioxidants. Methodology/Principal Findings: The present study was designed to evaluate the antileishmanial effect of cisplatin at higherdoses(5mgand2.5mg/kgbodyweight)anditscombinationwithdifferentantioxidants(vitaminC,vitaminEand silibinin) so as to eliminate the parasite completely and reduce the toxicity. In addition, various immunological, hematologicalandbiochemicalchangesinducedbyitinuninfectedandLeishmaniadonovaniinfectedBALB/cmicewere investigated. Conclusion/Significance: A significant reduction in parasite load, higher IgG2a and lower IgG1 levels, enhanced DTH responses,andgreaterconcentrationofTh1cytokines(IFN-c,IL-2)withaconcomitantdownregulationofIL-10andIL-4 pointed towards the generation of the protective Th1 type of immune response. A combination of cisplatin with antioxidants resulted in successful reduction of nephrotoxicity by normalizing the enzymatic levels of various liver and kidneyfunctiontests.Reductioninparasite