Lycopene and Melatonin Protection Against Methotrexate-induced Nephrotoxicity in Rats

Methotrexate (Mtx), an antifolate, is used as an anti-cancer drug in higher doses such as lymphoma, breast carcinoma, sarcoma, breast cancer (Choudhury et al., 2000; Miyazaki et al., 2003; Seigers et al., 2008; Findlay et al., 2008; D’Adamo, 2011) and also in lower doses in the treatment of rheumatic diseases, psoriasis, refractory inflammatory bowel disease since it has immunosuppressant effect (Peters et al., 2000; Gisondi and Girolomoni, 2007; Renna, 2014). However, nephrotoxicity, a native adverse effect of certain anticancer drugs, is also one of the complications of Mtx therapy (Asvadi et al., 2011; Lameire et al., 2011). It has been suggested that oxidative stress and inflammation may have role inthe pathogenesis of MTX-induced nephrotoxicity rather than blockage in folate synthesis in kidneys (Devrim et al., 2005; Asvadi et al., 2011). Lyc (Lyc) is a natural pigment, presented in tomato and other red fruits and vegetables such as watermelon, pink grape fruit (Clinton, 1998). It has many biochemical functions as a highly efficient antioxidant and free radical scavenging agent and inhibitor of proinflamatory and pro-thrombotic factors (Cohen, 2002; Tapiero et al., 2004; Velmurugan et al., 2004; Mordente et al., 2011). It is twice as effective as β-carotene and 10-fold more activethan α-tocopherol as an antioxidant (Di Mascio, 1989) that