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
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.
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
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.
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
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