Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

doi:10.3748/wjg.v20.i29.10158

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Aug 7, 2014; 20(29): 10158-10165
Published online Aug 7, 2014. doi: 10.3748/wjg.v20.i29.10158

Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

Sami Akbulut, Hulya Elbe, Cengiz Eris, Zumrut Dogan, Gulten Toprak, Emrah Otan, Erman Erdemli, Yusuf Turkoz

Sami Akbulut, Cengiz Eris, Emrah Otan, Liver Transplant Institute, Inonu University Faculty of Medicine, 44280 Malatya, Turkey

Hulya Elbe, Department of Histology and Embriology, Inonu University Faculty of Medicine, 44280 Malatya, Turkey

Zumrut Dogan, Department of Anatomy, Adiyaman University Faculty of Medicine, 02100 Adiyaman, Turkey

Gulten Toprak, Department of Biochemistry, Dicle University Faculty of Medicine, 21280 Diyarbakir, Turkey

Erman Erdemli, Yusuf Turkoz, Department of Biochemistry, Inonu University Faculty of Medicine, 44280 Malatya, Turkey

Author contributions: Akbulut S, Eris C, Dogan Z and Erdemli E performed all of experimental design and surgical procedures; Akbulut S, Elbe H and Otan E contributed to writing the paper and review of the literature; Elbe H provided histopathologic information and performed statistical analysis; Toprak G and Turkoz Y provided biochemical information.

Correspondence to: Sami Akbulut, Assistant Professor, FICS, FACS, Liver Transplant Institute, Inonu University Faculty of Medicine, 44280 Malatya, Turkey. akbulutsami@gmail.com

Telephone: +90-422-3410660 Fax: +90-422-3410036

Received: December 9, 2013
Revised: February 11, 2014
Accepted: April 8, 2014
Published online: August 7, 2014

Core Tip

Core tip: While the underlying mechanism of methotrexate (MTX)-induced hepatotoxicity remains to be fully elucidated, increases in oxidative stress have been linked to the effects of MTX; moreover, MTX-induced toxicity has been shown to be associated with increases in lipid peroxidation in various tissues, such as liver, using rat model systems. A few previous studies have shown that prophylactic delivery of antioxidant agents can prevent MTX-induced hepatotoxicity. Based on this information, we aimed to investigate the role of oxidative stress in MTX-induced hepatotoxicity and to evaluate the potential therapeutic effects of the cytoprotective antioxidants N-acetylcysteine, amifostine, and ascorbic acid.