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

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.

The Investigation of the Oxidative Stress-Related Parameters in High Doses Methotrexate-Induced Albino Wistar Rats

“…Levels of both enzymatic and non-enzymatic anti-oxidants are inhibited and the levels of oxidants increase in the testes, heart, liver, kidney, and gut tissues of laboratory animals given methotrexate [5]. It has further been reported that MTX-administration induces oxidative stress and significantly reduces antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase in liver, intestinal mucosa and spinal cord tissues of rats [27].…”

“…Because, it involved in several detoxification reactions in the organism and it is one of the most prominent non-enzymatic antioxidants [29,30]. Many studies have shown a decrease in the GSH level in the small intestine [5] and in liver [2,30] following MTX administration. The present study showed a highly significant reduction in cellular GSH level after MTX-treatment.…”

“…On the contrary, there are studies showing that with the addition of folic acid, the therapeutic effectiveness of methotrexate decreases [5].…”

“…and in the treatment of various inflammatory diseases [5,6]. It is also used for the treatment of multiple sclerosis, dermatomyositis, sarcoidosis, psoriasis, and rheumatoid arthritis, disorders causing inflammation.…”

“…It is therefore thought that antioxidant therapy may be useful in preventing or reducing hepatotoxicity due to methotrexate. Although these deleterious toxic effects of methotrexate can theoretically be reduced or prevented with the addition of folic acid to the treatment, there is yet no consensus on the subject [5]. On the contrary, there are studies showing that with the addition of folic acid, the therapeutic effectiveness of methotrexate decreases.…”