Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats Sinan Ince a,⇑ , Ismail Kucukkurt b , Hasan Huseyin Demirel c , Damla Arslan Acaroz b , Erten Akbel d , Ibrahim Hakki Cigerci e a Afyon Kocatepe University, Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, 03030 Afyonkarahisar, Turkey b Afyon Kocatepe University, Faculty of Veterinary Medicine, Department of Biochemistry, 03030 Afyonkarahisar, Turkey c Afyon Kocatepe University, Faculty of Veterinary Medicine, Department of Pathology, 03030 Afyonkarahisar, Turkey d Usak University, Usak Health Training School, 64100 Usak, Turkey e Afyon Kocatepe University, Faculty of Science and Arts, Department of Biology, 03030 Afyonkarahisar, Turkey highlights  B reduces cyclophosphamide (CYC) induced toxicity.  B inhibits lipid peroxidation and DNA damage in rats.  B regenerates CYC-induced histopathological changes in rat tissues.  B attenuates NO and restores SOD, CAT, and GSH in rats. article info Article history: Received 19 August 2013 Received in revised form 5 December 2013 Accepted 5 January 2014 Available online xxxx Keywords: Boron Cyclophosphamide Genotoxicity Lipid peroxidation Rat abstract The aim of the present study was to evaluate the possible protective effect of boron (B) on cyclophospha- mide (CYC) induced oxidative stress in rats. Totally, thirty Wistar albino male rats were fed standard rodent diet and divided into 5 equal groups: physiological saline was given intraperitoneally (i.p.) to the control group (vehicle treated), to the second group only 75 mg kg 1 CYC was given i.p. on the 14th d, and boron was administered (5, 10, and 20 mg kg 1 , i.p.) to the other groups for 14 d and CYC (75 mg kg 1 , i.p.) on the 14th d. CYC caused increase of malondialdehyde and decrease of glutathione lev- els, decrease of superoxide dismutase activities in erythrocyte and tissues, decrease of erythrocyte, heart, lung, and brain catalase, and plasma antioxidant activities. Also, CYC treatment caused to DNA damage in mononuclear leukocytes. Moreover, B exhibited protective action against the CYC-induced histopatholo- gical changes in tissues. However, treatment of B decreased severity of CYC-induced lipid peroxidation and genotoxicity on tissues. In conclusion, B has ameliorative effects against CYC-induced lipid peroxida- tion and genotoxicity by enhancing antioxidant defence mechanism in rat. Ó 2014 Elsevier Ltd. All rights reserved. 1. Introduction Cyclophosphamide (N,N-Bis(2-chloroethyl)tetrahydro-2H- 1,3,2-oxazaphosphorin-2-amine 2-oxide; CYC), is a cytotoxic bifunctional alkylating agent, belongs to the class of nitrogen mus- tards (Dollery, 1999; Tripathi and Jena, 2008). CYC is widely used at high dose for chemotherapy of various forms of cancer (bron- chial, breast and ovarian cancer, lymphomas, leukemias, etc.) and at low dose for treatment of autoimmune diseases (rheumatoid arthritis), and also used as immunosuppressant after organ transplantations (bone marrow transplantations) (Jolivet et al., 1983; Kuo et al., 2003; Buerge et al., 2006). In clinical application, it is important to prevent DNA damage of normal cells which is in- duced by CYC (Tripathi and Jena, 2009). Recent studies suggest that CYC generates reactive oxygen species like superoxide anion, hy- droxyl radical and hydrogen peroxide (H 2 O 2 ) during its oxidative metabolism, and depresses the antioxidant defense mechanisms in the liver (Bhattacharya et al., 2003; Stankiewicz et al., 2002). These free radicals may attack soluble cell compounds as well as membranes, eventually leading to the impairment of cell functions and cytolysis (Bergendi et al., 1999). Boron (B) is a mineral substance found in nature. A side from its traditional use in the health care system, B is widely used in http://dx.doi.org/10.1016/j.chemosphere.2014.01.038 0045-6535/Ó 2014 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. Tel.: +90 2722281312/142; fax: +90 2722281349. E-mail address: since@aku.edu.tr (S. Ince). Chemosphere xxx (2014) xxx–xxx Contents lists available at ScienceDirect Chemosphere journal homepage: www.elsevier.com/locate/chemosphere Please cite this article in press as: Ince, S., et al. Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats. Che- mosphere (2014), http://dx.doi.org/10.1016/j.chemosphere.2014.01.038