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Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 2, pp. 70-80
doi:10.32527/2017/101427

Role of Ketotifen in Methotrexate-induced Nephrotoxicity in Rats

Marwa M. M. Refaie1, Salwa A. Ibrahim1, Shaimaa A. Sadek2, and Aly M. Abdelrahman1

1Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt

2Department of Pathology, Faculty of Medicine, Minia University, Minia, Egypt

Copyright © 2017 Marwa M. M. Refaie 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.

Abstract

Methotrexate (MTX) is a chemotherapeutic agent that interrupts folate metabolism by inhibition of dihydrofolate reductase; a required precursor for co-factors share in macromolecule biosynthesis. MTX is complicated by marked nephrotoxicity especially in high doses so that in current study the possible protective effect of an anti-inflammatory drug (ketotifen) on MTX-induced nephrotoxicity and the mechanisms involved were investigated. Two doses of ketotifen (1 and 10mg/kg) were given orally to rats for 14 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal (ip) injection of MTX (20 mg/kg) at day 11th of the experiment. Serum urea, creatinine, renal reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NOx), catalase, superoxide dismutase (SOD) activity, caspase-3, tumor necrosis factor alpha (TNFα), nuclear factor kappa B (NFκB) immunoexpressions, and renal histopathology were measured. Results showed that ketotifen succeeded in reversing MTX-induced nephrotoxicity to levels insignificant from control.

Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 2, pp. 70-80
doi:10.32527/2017/101427

Role of Ketotifen in Methotrexate-induced Nephrotoxicity in Rats

Marwa M. M. Refaie1, Salwa A. Ibrahim1, Shaimaa A. Sadek2, and Aly M. Abdelrahman1

1Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt

2Department of Pathology, Faculty of Medicine, Minia University, Minia, Egypt

Copyright © 2017 Marwa M. M. Refaie 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.

Abstract

Methotrexate (MTX) is a chemotherapeutic agent that interrupts folate metabolism by inhibition of dihydrofolate reductase; a required precursor for co-factors share in macromolecule biosynthesis. MTX is complicated by marked nephrotoxicity especially in high doses so that in current study the possible protective effect of an anti-inflammatory drug (ketotifen) on MTX-induced nephrotoxicity and the mechanisms involved were investigated. Two doses of ketotifen (1 and 10mg/kg) were given orally to rats for 14 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal (ip) injection of MTX (20 mg/kg) at day 11th of the experiment. Serum urea, creatinine, renal reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NOx), catalase, superoxide dismutase (SOD) activity, caspase-3, tumor necrosis factor alpha (TNFα), nuclear factor kappa B (NFκB) immunoexpressions, and renal histopathology were measured. Results showed that ketotifen succeeded in reversing MTX-induced nephrotoxicity to levels insignificant from control.

Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 2, pp. 70-80
doi:10.32527/2017/101427

Role of Ketotifen in Methotrexate-induced Nephrotoxicity in Rats

Marwa M. M. Refaie1, Salwa A. Ibrahim1, Shaimaa A. Sadek2, and Aly M. Abdelrahman1

1Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt

2Department of Pathology, Faculty of Medicine, Minia University, Minia, Egypt

Copyright © 2017 Marwa M. M. Refaie 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.

How to Cite this Article

Marwa M. M. Refaie, Salwa A. Ibrahim, Shaimaa A. Sadek, and Aly M. Abdelrahman, “Role of Ketotifen in Methotrexate-induced Nephrotoxicity in Rats,” Egyptian Journal of Basic and Clinical Pharmacology, Vol. 7, Issue 2, pp. 70-80, 2017. doi:10.32527/2017/101427