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. 2015 Aug;10(2):503-507.
doi: 10.3892/etm.2015.2542. Epub 2015 Jun 3.

Silibinin attenuates methotrexate-induced pulmonary injury by targeting oxidative stress

Serdar Kalemci  1 , Yasar Topal  2 , Serkan Yasar Celik  3 , Nigar Yilmaz  4 , Halil Beydilli  5 , Mehmet Ilkay Kosar  6 , Nigar Dirican  7 , Irfan Altuntas  4
Affiliations

Silibinin attenuates methotrexate-induced pulmonary injury by targeting oxidative stress

Serdar Kalemci et al. Exp Ther Med. 2015 Aug.

Abstract

The aim of the present study was to assess the protective effect of silibinin against methotrexate (MTX)-induced pulmonary toxicity. Rats were divided into four groups (MTX, MTX + silibinin, silibinin and control. MTX was injected intraperitoneally (i.p) into female Wistar rats (10 mg/kg/day for 3 days), which resulted in significant increases in the serum levels of alanine aminotransferase, aspartate aminotransferase and oxidant enzymes, including nitric oxide and myeloperoxidase. Furthermore, significant reductions were detected in the serum activity levels of the antioxidative enzymes, glutathione peroxidase and superoxide dismutase, when compared with the control group. However, administration of silibinin (100 mg/kg/day for 10 days, i.p.) was shown to ameliorate the MTX-induced pulmonary toxicity, as indicated by the normalization of the oxidative stress parameters. Furthermore, silibinin treatment was demonstrated to reduce the histopathological changes associated with MTX. In conclusion, silibinin exhibited protective effects against MTX-induced pulmonary toxicity, which may be attributed to its antioxidant activity.

Keywords: antioxidant; methotrexate; pulmonary toxicity; rat; silibinin.

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Figures

Figure 1.
Figure 1.
Histological analysis of the control group pulmonary tissue (hematoxylin and eosin; magnification, x40).
Figure 2.
Figure 2.
Histological analysis of the silibinin group pulmonary tissue (hematoxylin and eosin; magnification, x100).
Figure 3.
Figure 3.
Histological analysis of the methotrexate group pulmonary tissue. (A) Interstitial lymphocytic inflammation and interstitial fibrosis were observed in the pulmonary tissue (hematoxylin and eosin; magnification, x100). (B) Type 2 pneumocyte hyperplasia was also observed in the tissue (magnification, x200).
Figure 4.
Figure 4.
Histological analysis of the methotrexate + silibinin group pulmonary tissue. Slight interstitial lymphocytic inflammation was observed in the pulmonary tissue, in addition to focal type 2 pneumocyte hyperplasia. Interstitial fibrosis was not observed (hematoxylin and eosin; magnification, x200).
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