title: The effects of valsartan on renal glutathione peroxidase expression in alleviation of cyclosporine nephrotoxicity in rats.
abstract: Introduction:Nephrotoxicity as a side effect caused by the immunosuppressive drug, cyclosporine-A (CsA), can be a major problem in transplant medicine. Oxidative stress may play an important role in the CsA-induced nephrotoxicity. It has been shown that the antihypertensive drug, valsartan (Val), has also renoprotective effects but, its molecular mechanism is largely unknown. In the present study, it was aimed to evaluate the Val effect in the alleviation of CsA nephrotoxicity via probable renal glutathione peroxidase (GPx) upregulation and oxidative stress decrease.Methods:Thirty-two Sprague-Dawley rats were divided into four groups based on CsA and/or Val administration: group A (Control, 1 mL/kg/day of olive oil as vehicle), group B (CsA, 30 mg/kg/day), group C (CsA+Val, 30+30 mg/kg/day), and group D (Val, 30 mg/kg/day). After the administration period (six weeks), renal GPx expression was evaluated by real-time polymerase chain reaction (PCR). Plasma levels of GPx and 8-Hydroxydeoxyguanosine (8-OHdG) were measured by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) and protein carbonyl groups (PCG) were measured by spectrophotometer. Plasma levels of urea and creatinine were measured by an autoanalyzer.Results:CsA treatment led to the decrease in renal expression and plasma levels of GPx in comparison to other study groups. Rats received CsA were detected to have significantly (p<0.05) higher plasma 8-OHdG, MDA, PCG, urea, and creatinine levels in comparison to other groups. Plasma urea and creatinine levels were negatively correlated with renal GPx expression and positively correlated with the oxidative stress markers.Conclusion:Administration of Val may result in attenuating the nephrotoxic side effect of CsA via probable renal GPx upregulation, and subsequently oxidative stress decrease.
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran ; Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran ; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Sina
authors.initials: S
authors.lastname: Raeisi
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Ghorbanihaghjo
authors.affiliation: Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Argani
authors.affiliation: Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Siavoush
authors.initials: S
authors.lastname: Dastmalchi
authors.affiliation: Division of Clinical Laboratory, Tabriz Children's Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Babollah
authors.initials: B
authors.lastname: Ghasemi
authors.affiliation: Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Teimour
authors.initials: T
authors.lastname: Ghazizadeh
authors.affiliation: Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Nadereh
authors.initials: N
authors.lastname: Rashtchizadeh
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mehran
authors.initials: M
authors.lastname: Mesgari Abbasi
authors.affiliation: Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Bargahi
authors.affiliation: Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mahboob
authors.initials: M
authors.lastname: Nemati
authors.affiliation: Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Mota
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Amir Mansour
authors.initials: AM
authors.lastname: Vatankhah
keywords: Cyclosporine-A; Glutathione peroxidase; Oxidative stress; Transplantation; Valsartan