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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 3281670, 10 pages
Research Article

Diosmin Attenuates Methotrexate-Induced Hepatic, Renal, and Cardiac Injury: A Biochemical and Histopathological Study in Mice

1Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt
2Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
3Faculty of Medicine, Ain Shams University, Cairo, Egypt
4Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
5Department of Zoology and Entomology, College of Science, Helwan University, Cairo, Egypt

Correspondence should be addressed to Mohamed M. Abdel-Daim; ge.ude.zeus.tev@m.miadledba

Received 22 March 2017; Revised 8 June 2017; Accepted 12 June 2017; Published 27 July 2017

Academic Editor: Francisco J. Romero

Copyright © 2017 Mohamed M. Abdel-Daim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The current study was designed to investigate the beneficial role of diosmin, a biologically active flavonoid, against methotrexate- (MTX-) induced hepatic, renal, and cardiac injuries in mice. Male Swiss albino mice received a single intraperitoneal injection of MTX (at 20 mg/kg, body weight) either alone or in combination with oral diosmin (at 50 or 100 mg/kg body weight, for 10 days). Serum was used to evaluate tissue injury markers, while hepatic, renal, and cardiac tissue samples were obtained for determination of antioxidant activity as well as histopathological examination. Diosmin treatment ameliorated the MTX-induced elevation of serum alkaline phosphatase, aminotransferases, urea, creatinine, lactate dehydrogenase, and creatine kinases as well as plasma proinflammatory cytokines (interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha). Additionally, both diosmin doses significantly reduced tissue levels of malondialdehyde and nitric oxide and increased those of glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase, compared to the MTX-intoxicated group. Histopathological examination showed that diosmin significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of hepatic, renal, and cardiac tissues. Based on these findings, diosmin may be a promising agent for protection against MTX-induced cytotoxicity in patients with cancer and autoimmune diseases.