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Effects of Angiotensin II Receptor Blockade on Soluble Klotho and Oxidative Stress in Calcineurin Inhibitor Nephrotoxicity in Rats.
- Source :
-
Iranian journal of kidney diseases [Iran J Kidney Dis] 2016 Nov; Vol. 10 (6), pp. 358-363. - Publication Year :
- 2016
-
Abstract
- Introduction: Calcineurin inhibitor nephrotoxicity is major problem after organ transplantation. It is multifactorial, but oxidative stress may have an important role in this process. It has been shown that angiotensin II receptor blockers have renoprotective effects but their molecular mechanism is largely unknown. Antioxidative effect is an important role of the recently known anti-aging protein, klotho. This study aimed to evaluate effect of valsartan in alleviation of cyclosporine A nephrotoxicity via a probable increase in serum klotho levels or decreasing oxidative stress.<br />Materials and Methods: Thirty-two Sprague-Dawley rats were divided into 4 groups to receive 1 mL/kg/d of olive oil as control; 30 mg/kg/d of cyclosporine; 30 mg/kg/d of cyclosporine and 50 mg/kg/d of valsartan; and 50 mg/kg/d of valsartan. After the 6 weeks of administration period, serum levels of klotho and 8-hydroxydeoxyguanosine were measured using an enzyme-linked immunosorbent assay. Serum malondialdehyde level was measured spectrophotometrically.<br />Results: The mean serum level of klotho was significantly lower in the cyclosporine group compared with control and valsartan groups. Klotho level in the valsartan group was significantly higher than those in the other groups. The cyclosporine group was detected to have significantly higher serum 8-hydroxydeoxyguanosine and malondialdehyde levels compared with the other study groups. The levels of klotho were negatively correlated with 8-hydroxydeoxyguanosine and malondialdehyde levels.<br />Conclusions: Administration of valsartan may lead to attenuation of the nephrotoxic side effect of cyclosporine via enhancing klotho and decreasing oxidative stress levels.
- Subjects :
- 8-Hydroxy-2'-Deoxyguanosine
Animals
Deoxyguanosine analogs & derivatives
Deoxyguanosine blood
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Glucuronidase blood
Kidney Diseases blood
Klotho Proteins
Malondialdehyde blood
Random Allocation
Rats
Rats, Sprague-Dawley
Spectrophotometry
Angiotensin Receptor Antagonists pharmacology
Calcineurin Inhibitors toxicity
Cyclosporine toxicity
Glucuronidase drug effects
Kidney drug effects
Kidney Diseases chemically induced
Oxidative Stress drug effects
Valsartan pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1735-8604
- Volume :
- 10
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Iranian journal of kidney diseases
- Publication Type :
- Academic Journal
- Accession number :
- 27903993