Renoprotective effects of montelukast in an experimental model of cisplatin nephrotoxicity in rats

Renal toxicity is one of the most severe complications that can occur with cisplatin (CIS) administration in cancer patients. Montelukast (ML) renoprotective outcome contrary to CIS‐drawn nephrotoxicity remains obscure. Therefore, adult male Sprague–Dawley rats were orally given ML (10 and 20 mg/kg/...

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Published in:Journal of biochemical and molecular toxicology 2017-12, Vol.31 (12), p.n/a
Main Authors: Gad, Amany M., El‐Raouf, Ola M. Abd, El‐Sayeh, Bahia M., Fawzy, Hala M., Abdallah, Dalaal M.
Format: Article
Language:English
Subjects:
Acetates - pharmacology
Acetates - therapeutic use
Acute Kidney Injury - chemically induced
Acute Kidney Injury - prevention & control
Animals
apoptosis
Cancer
Caspase
Caspase 3 - metabolism
Caspase-3
Chemotherapy
Cisplatin
Cisplatin - toxicity
Complications
Creatinine
Drug Evaluation, Preclinical
Endothelin 1
Endothelins
Guards
Inflammation
Injury prevention
Kidney - drug effects
Kidney - enzymology
Kidney - pathology
Leukotriene Antagonists - pharmacology
Leukotriene Antagonists - therapeutic use
Male
Monocyte chemoattractant protein
Monocyte chemoattractant protein 1
Montelukast
nephrotoxicity
Nitric oxide
Quinolines - pharmacology
Quinolines - therapeutic use
Rats
Rats, Sprague-Dawley
Rodents
Toxicity
Urea
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Summary:Renal toxicity is one of the most severe complications that can occur with cisplatin (CIS) administration in cancer patients. Montelukast (ML) renoprotective outcome contrary to CIS‐drawn nephrotoxicity remains obscure. Therefore, adult male Sprague–Dawley rats were orally given ML (10 and 20 mg/kg/day) 5 days before and after single CIS (5 mg/kg; i.p.) treatment. ML returned blood urea nitrogen, as well as serum creatinine and gamma glutamyl transferase that were elevated by CIS to normal level. The improved kidney function tests corroborated the attenuation of CIS renal injury at the microscopical level. It also reduced serum/renal nitric oxide and renal hemeoxygenase‐1. Meanwhile, ML hindered the raised levels of serum endothelin‐1, serum and renal tumor necrosis factor‐α, and monocyte chemoattractant protein‐1. These effects were associated by deceased caspase‐3 expression in kidney after ML treatment. In conclusion, ML guards against CIS‐induced nephrotoxicity via anti‐inflammatory and antiapoptotic properties.
ISSN:1095-6670
1099-0461
DOI:10.1002/jbt.21979