title: The protective effect of trimetazidine against cisplatin-induced nephrotoxicity in rats.
abstract: Nephrotoxicity is a dose-limiting side effect of cisplatin (CSP). The study investigated the possible protective role of trimetazidine (TMZ) against CSP-induced nephrotoxicity in rats. Rats were divided into four groups; control, TMZ, CSP, and CSP + TMZ. The CSP group showed significant deterioration in kidney function with structural changes in the form of interstitial hemorrhage, glomeruli shrinkage and peritublar capillary congestion, tubular cells vacuolation, pyknosis, shedding and necrosis, and inflammatory cell infiltrates, all indicating renal damage. CSP also caused a significant increase in the lipid peroxidation marker malondialdehyde (MDA) levels, renal nuclear factor kappa B (NF-κB) DNA-binding activity and protein expression, and tumor necrosis factor alpha (TNF-α) and IL-6 levels. Treatment with TMZ before and after CSP injection produced significant improvement of kidney function and histopathology. TMZ treatment also significantly attenuated CSP-induced oxidative stress and suppressed elevated levels of TNF-α and IL-6 and NF-κB expression and its DNA-binding activity caused by CSP administration. TMZ has a protective effect against CSP-induced nephrotoxicity mediated by reduction of oxidative stress and attenuation of CSP-induced inflammation.
authors.affiliation: a Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia.|b Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: Nagla A
authors.initials: NA
authors.lastname: El-Sherbeeny
authors.affiliation: c Department of Anatomy, Faculty of Medicine, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia.|d Department of Histology & Cell Biology, Faculty of Medicine, Mansoura University, Al Mansoura, Egypt.
authors.forename: Ghalia M
authors.initials: GM
authors.lastname: Attia
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D002945:Cisplatin / Q000633:toxicity*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D020011:Protective Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014292:Trimetazidine / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D018836:Inflammation Mediators; D020011:Protective Agents; D014665:Vasodilator Agents; D014292:Trimetazidine; D002945:Cisplatin
keywords: NF-κB; cisplatin; cisplatine; nephrotoxicity; néphrotoxicité; oxidative stress; stress oxydatif; trimetazidine; trimétazidine