Evaluation of drug-induced tissue injury by measuring alanine aminotransferase (ALT) activity in silkworm hemolymph.docVIP

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Evaluation of drug-induced tissue injury by measuring alanine aminotransferase (ALT) activity in silkworm hemolymph.doc

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Evaluation of drug-induced tissue injury by measuring alanine aminotransferase (ALT) activity in silkworm hemolymph

Inagakietal.BMCPharmacologyandToxicology2012,13:13 /2050-6511/13/13 RESEARCH ARTICLE OpenAccess Evaluationofdrug-inducedtissueinjuryby measuringalanineaminotransferase(ALT)activity insilkwormhemolymph YoshinoriInagaki1,YasuhikoMatsumoto1,KeikoKataoka2,NaoyaMatsuhashi2andKazuhisaSekimizu1,2* Abstract Background:Ourpreviousstudiessuggestsilkwormscanbeusedasmodelanimalsinsteadofmammalsin pharmacologicstudiestodevelopnoveltherapeuticmedicines.Weexaminedtheusefulnessofthesilkwormlarvae Bombyxmoriasananimalmodelforevaluatingtissueinjuryinducedbyvariouscytotoxicdrugs.Drugsthatinduce hepatotoxiceffectsinmammalswereinjectedintothesilkwormhemocoel,andalanineaminotransferase(ALT) activitywasmeasuredinthehemolymph1daylater. Results:InjectionofCCl4intothehemocoelledtoanincreaseinALTactivity.TheincreaseinALTactivitywas attenuatedbypretreatmentwithN-acetyl-L-cysteine.Injectionofbenzoicacidderivatives,ferricsulfate,sodiumvalproate, tetracycline,amiodaronehydrochloride,methyldopa,ketoconazole,pemoline(Betanamin),N-nitroso-fenfluramine,and D-galactosaminealsoincreasedALTactivity. Conclusions:Thesefindingsindicatethatsilkwormsareusefulforevaluatingtheeffectsofchemicalsthatinducetissue injuryinmammals. Keywords:Silkworm,Alanineaminotransferase,Tissueinjury,Animalmodel Background Althoughinvertebrate animalssuchasCaenorhabditis Tissueinjuryinducedbychemicalsinmammals,includ- elegans (C. elegans) and Drosophila larvae have been inghumans,isassociatedwiththerapiddevelopmentof proposed as model animals for evaluating bacterial severe impairment of the organs involved in detoxifica- pathogenicityandtherapeuticeffectsofantibiotics,their tion,e.g.,fulminanthepaticfailure[1].Therefore,assess- bodysizesaretoosmalltoinjectafixedamountofsam- mentofchemical-inducedtissueinjuryiscrucialindrug ple [5,6]. Large insect larvae can be easily injected into discovery. the midgut or subcutaneously with sample solution In the development of novel therapeutic medicines, usingasyr