Research Article | OPEN ACCESS
Different Protective Effects of Trimetazidine against Renal Ischemia/Reperfusion Injury in Rats
1Amany A. Azouz, 1, 2Hany A. Omar, 1Amira M. Abo-yousef, 3Gamal A. El-Sherbiny and 4, 5Hekma A. Abdel-Latif
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University,
Beni-Suef, 62514, Egypt
2Sharjah Institute for Medical Research, College of Pharmacy, Department of Pharmacology, University of Sharjah, Sharjah 27272, UAE
3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafr El-sheikh University, Kafr El-sheikh, Egypt
2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Umm Al Qura University, Makkah, KSA
5Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University,
Cairo, 11432, Egypt
British Journal of Pharmacology and Toxicology 2015 3:64-69
Received: February 8, 2015 | Accepted: March 1, 2015 | Published: July 20, 2015
Abstract
Ischemia/Reperfusion (I/R) injury during kidney transplantation is a major clinical problem which leads to delayed graft function or even graft rejection. Therefore, the aim of the present study was to explore the possible protective effects of trimetazidine, an anti-ischemic agent, against experimentally-induced renal I/R injury in rats. Ischemia was induced by bilateral clamping of renal pedicles for 45 min followed by 24 h of reperfusion. Trimetazidine (10 mg/kg) was orally administered twice daily for 14successive days before induction of ischemia. At the end of the reperfusion period (24 h), blood and renal tissue samples were collected for biochemical and histopathological examination. Trimetazidine showed nephroprotective effects as evidenced by significant decrease in blood urea nitrogen and serum creatinine levels as well as renal content of tumor necrosis factor-α, malondialdehyde and myeloperoxidase. In addition, trimetazidine replenished renal content of adenosine triphosphate and glutathione that was confirmed by the improvement in histopathological features. The current study demonstrated the nephroprotective effects of trimetazidine against renal I/R injury, which might be mediated through its anti-ischemic, anti-inflammatory or antioxidant activities.
Keywords:
Anti-inflammatory, anti-ischemic, antioxidant, renal ischemia/reperfusion, trimetazidine,
References
-
Arab, H.H., S.A. Salama, A.H. Eid, H.A. Omar, S.A. Arafa and I.A. Maghrabi, 2014. Camel's milk ameliorates TNBS-induced colitis in rats via downregulation of inflammatory cytokines and oxidative stress. Food Chem. Toxicol., 69: 294-302.
CrossRef PMid:24788059 -
Avlan, D., L. Tamer, L. Ayaz, A. Polat, C. Öztürk, H. Özturhan, H. Çamdeviren and S. Aksöyek, 2006. Effects of trapidil on renal ischemia-reperfusion injury. J. Pediatr. Surg., 41(10): 1686-1693.
CrossRef PMid:17011270 -
Bancroft, J.D. and M. Gamble (2008). Theory and practice of histological techniques. 6th Edn., Churchill Living stone Elsevier, London.
-
Bradley, P.P., D.A. Priebat, R.D. Christensen and G. Rothstein, 1982. Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J. Invest. Dermatol., 78(3): 206-209.
CrossRef PMid:6276474 -
Chatterjee, P.K., 2007. Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: A comprehensive review. Naunyn Schmiedebergs Arch. Pharmacol., 376(1-2): 1-43.
CrossRef PMid:18038125 -
Domanski, L., T. Sulikowski, K. Safranow, A. Pawlik, M. Olszewska, D. Chlubek, E. Urasinska and K. Ciechanowski, 2006. Effect of trimetazidine on the nucleotide profile in rat kidney with ischemia-reperfusion injury. Eur. J. Pharm. Sci., 27(4): 320-327.
CrossRef PMid:16387483 -
Engelhardt, G. and D. Homma, 1996. Effects of acetylsalicylic acid, paracetamol and caffeine and a combination of these substances on kidney glutathione levels. Arzneimittelforschung, 46(5): 513-518.
PMid:8737638 -
Grossini, E., C. Molinari, P. Pollesello, G. Bellomo, G. Valente, D. Mary, G. Vacca and P. Caimmi, 2012. Levosimendan protection against kidney ischemia/reperfusion injuries in anesthetized pigs. J. Pharmacol. Exp. Ther., 342(2): 376-388.
CrossRef PMid:22566668 -
Hagar, H.H., E. Tawab and R. Abd, 2012. Cysteinyl leukotriene receptor antagonism alleviates renal injury induced by ischemia-reperfusion in rats. J. Surg. Res., 178(1): e25-e34.
CrossRef PMid:22487384 -
Lowry, O.H., J.V. Passonneau, F.X. Hasselberger and D.W. Schulz, 1964. Effect of ischemia on known substrates and cofactors of the glycolytic pathway in brain. J. Biol. Chem. 239(1): 18-30.
PMid:14114842 -
Matthijsen, R.A., D. Huugen, N.T. Hoebers, B. De Vries, C.J. Peutz-Kootstra, Y. Aratani and et al., 2007. Myeloperoxidase is critically involved in the induction of organ damage after renal ischemia reperfusion. Am. J. Pathol., 171(6): 1743-1752.
CrossRef PMid:18055546 PMCid:PMC2111099 -
Mehany, H.A., A.M. Abo-youssef, L.A. Ahmed, E.S.A. Arafa and H.A. Abd El-Latif, 2013. Protective effect of vitamin E and atorvastatin against potassium dichromate-induced nephrotoxicity in rats. Beni-Suef Univ., J. Basic Appl. Sci., 2(2): 96-102.
-
Meldrum, K.K., D.R. Meldrum, X. Meng, L. Ao and A.H. Harken, 2002. TNF-a-dependent bilateral renal injury is induced by unilateral renal ischemia-reperfusion. Am. J. Physiol. Heart Circ. Physiol., 282(2): H540-H546.
CrossRef PMid:11788401 -
Morin, D., T. Hauet, M. Spedding and J.P. Tillement, 2001. Mitochondria as target for antiischemic drugs. Adv. Drug Deliv. Rev., 49(1): 151-174.
CrossRef -
Onbasili, A.O., Y. Yeniceriglu, P. Agaoglu, A. Karul, T. Tekten, H. Akar and G. Discigil, 2007. Trimetazidine in the prevention of contrast-induced nephropathy after coronary procedures. Heart, 93(6): 698-702.
CrossRef PMid:17065180 PMCid:PMC1955192 -
Salama, S.A., H.A. Omar, I.A. Maghrabi, M.S. AlSaeed and E.L.T. Ae, 2014. Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats. Toxicol. Appl. Pharmacol., 274(1): 1-6.
CrossRef PMid:24215938 -
Sulikowski, T., L. Domanski, K. Ciechanowski, G. Adler, A. Pawlik, K. Safranow, V. Dziedziejko, D. Chlubek and A. Ciechanowicz, 2008. Effect of trimetazidine on xanthine oxidoreductase expression in rat kidney with ischemia-reperfusion injury. Arch. Med. Res., 39(4): 459-462.
CrossRef PMid:18375259 -
Uchiyama, M. and M. Mihara, 1978. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal. Biochem., 86(1): 271-278.
CrossRef -
Yun, Y., W. Duan, P. Chen, H. Wu, Z. Shen, Z. Qian and D. Wang, 2009. Ischemic postconditioning modified renal oxidative stress and lipid peroxidation caused by ischemic reperfusion injury in rats. Transpl. Proc., 41(9): 3597-3602.
CrossRef PMid:19917351
Competing interests
The authors have no competing interests.
Open Access Policy
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Copyright
The authors have no competing interests.
|
|
![](http://www.maxwellsci.com/images/BJPT-maxw.jpg) |
ISSN (Online): 2044-2467
ISSN (Print): 2044-2459 |
![Submit Manuscript](../images/sub.jpg) |
Information |
|
|
|
Sales & Services |
|
|
|