Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses

The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent, narrows the therapeutic window despite its clinical usefulness. In the present study, we determined whether taurine protected against DOX-induced hepatic injury, and explored the molecular mechanisms underlying the suppr...

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Veröffentlicht in:Anti-cancer drugs 2016-01, Vol.27 (1), p.17-23
Hauptverfasser: Nagai, Katsuhito, Fukuno, Shuhei, Oda, Ayano, Konishi, Hiroki
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container_end_page 23
container_issue 1
container_start_page 17
container_title Anti-cancer drugs
container_volume 27
creator Nagai, Katsuhito
Fukuno, Shuhei
Oda, Ayano
Konishi, Hiroki
description The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent, narrows the therapeutic window despite its clinical usefulness. In the present study, we determined whether taurine protected against DOX-induced hepatic injury, and explored the molecular mechanisms underlying the suppressive effects of taurine in terms of alterations in oxidative stress and apoptotic responses. DOX-induced body weight loss was completely suppressed by taurine treatment. Elevations in the serum activity levels of lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase by DOX were also dose-dependently attenuated by a concurrent treatment with taurine. Superoxide dismutase activity and reduced glutathione content in the liver were decreased following the administration of DOX, whereas these changes were suppressed when 10 mg/kg taurine was given in combination with DOX. Taurine attenuated the increased expression of mRNAs for Fas and Bax after DOX exposure. Furthermore, the formation of cleaved caspase-3 protein in the group given DOX with taurine was lower than that in the group treated with DOX alone. Our results suggest that taurine can protect against DOX-induced acute hepatic damage, the underlying mechanism of which is attributable to the suppression of oxidative stress and apoptotic responses.
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subjects Alanine Transaminase - metabolism
Animals
Antibiotics, Antineoplastic - toxicity
Apoptosis - drug effects
Aspartate Aminotransferases - metabolism
Chemical and Drug Induced Liver Injury - metabolism
Chemical and Drug Induced Liver Injury - pathology
Chemical and Drug Induced Liver Injury - prevention & control
Doxorubicin - toxicity
Glutathione - metabolism
L-Lactate Dehydrogenase - metabolism
Male
Mice
Oxidative Stress - drug effects
Superoxide Dismutase - metabolism
Taurine - therapeutic use
title Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses
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