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The effect of mirtazapine on methotrexate-induced toxicity in rat liver

Bunyami Ozogul^a, Abdullah Kisaoglu^a, Mehmet Ibrahim Turan^b,*, Durdu Altuner^c, Ebru Sener^d, Nihal Cetin^e, Cengiz Ozturk^e,f

 
ABSTRACT:     Methotrexate is used as a chemotherapeutic agent and its anti-oxidant activity is used to treat many cancer types. This study conducts a biochemical and histopathological investigation into whether mirtazapine has a protective effect on methotrexate-induced hepatotoxicity in rats. Distilled water was given to a healthy group intraperitoneally. Methotrexate alone was injected in the control group, again intraperitoneally. Mirtazapine and, 1 h later, methotrexate were given to the rats in the final group. This procedure was repeated over 7 days. In the control group rats receiving methotrexate, blood AST, ALT, and LDH levels were 227±3 µmol/l, 85±2 µmol/l, and 357±13 µmol/l, respectively. In the rats receiving mirtazapine and methotrexate, these values were 152±3 µmol/l, 25±1 µmol/l, and 141±15 µmol/l. In the healthy rat group, AST, ALT, and LDH levels were 136 µmol/l, 20 µmol/l, and 133 µmol/l, respectively. Histopathologically, apoptotic bodies with condensed cytoplasm, peripheral, and pyknotic nuclei in the hepatocytes, focal necrosis and intense inflammation in the interstitial areas were present in the control group. In the methotrexate and mirtazapine group, there were no apoptotic bodies or inflammation, only isolated necrosis in the hepatocytes. In conclusion, mirtazapine protected the liver against methotrexate toxicity.

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* Corresponding author, E-mail: turan78tr@hotmail.com

Received 18 Dec 2012, Accepted 20 Mar 2013