HİLMİ DEMİRKIRAN, NİMET ŞENOĞLU, HAFİZE ÖKSÜZ, Zafer DOĞAN, MEHMET FATİH YÜZBAŞIOĞLU, Ertan BÜLBÜLOĞLU, FATMA İNANÇ TOLUN, MURAT ARAL, Harun ÇIRALIK, MUSTAFA GÖKSU, CEVDET YARDIMCI

The Effects of Different Doses of Ketamine on Renal Ischemia/Reperfusion Injury in Rats

In the patients who have perioperative renal failure risk, anesthetical substances should be choosen with caution to protect the function of kidneys. Ketamine, an anesthetic induction agent, is generally used in patients with severe hypotension or respiratory depression. We aimed to evaluate the different doses of ketamine’s effects on ischemia/reperfusion (I/R) damage mediated by free radicals in rats. Materials and methods: In this study, 42 Wistar albino male rats were splitted randomly into 7 different groups. In the ketamine group, ketamine was applied intraperitoneally (IP) in different doses (3 mg kg־ 1, 10 mg kg־ 1, 30 mg kg־ 1, 60 mg ־kg 1, 80 mg kg־ 1) on the 45 th minutes. Clamps were opened at the end of 60 minutes ischemia period. At the end of the reperfusion period, renal tissue and blood sample s were taken from the rats. In the plasma samples, pro-inflammatory biomarkers [Interleukin (IL)-1β, IL-6, tumour necrosis factor alpha (TNF-α)] were analysed. In renal tissue samples, antioxidating activities [Superoxide dismutase (SOD), glutathione perox idase (GPx) and nitric oxide (NO)] and lipid peroxidation product “Malondialdehyde (MDA)” levels were studied biochemically. Renal tissue damage was evaluated histopathologically. There were no differences among the beneficial effects of ketamine given gro ups (10-30-60-80 mg kg־ 1 doses) before reperfusion in the way of antioxidant activities, pro-inflammatory markers and lipid peroxidation product. When ketamin was applied in 3 mg kg־ 1 there were beneficial effects on tissues in the way of SOD, GPx, NO, MDA values and histopathologically (p

PDF

___

1. Onal A, Astarcıoglu H, Ormen M, Atila K, Sarioglu S. The beneficial effect of L-carnitine in rat renal ischemia-reperfusion injury. Ulus Travma Derg 2004; 10: 160-167.

2. Yousefipour Z, Oyekan A, Newaz M: Interaction of oxidative stress, nitric oxide and peroxisome proliferator activated receptor gamma in acute renal failure. Pharmacol Ther 2010; 125: 436-445

3. Akkuş İ. Serbest radikaller ve fizyopatolojik etkileri. Konya: Mimoza Yayınları 1995: 3-95.

4. Kandilci HB, Gümüşel B. Akciğerlerde iskemireperfüzyon hasarı ve iskemik önkoşullama (Ischemiareperfusion Injury and Ischemic Preconditioning in the Lungs. Hacettepe Dergisi 2005; 25: 35-49.

5. Teke Z, Kabay B, Özden A. İskemi-reperfüzyon hasarının patofizyolojisi. Pamukkale Tıp Dergisi 2008; 1: 65-72.

6. Başgül E, Çeliker V. Yeniden güncelleşen bir ilaç: Ketamin. Anesteziyoloji Dergisi 2004; 12: 7-15.

7. Wu Y, Li W, Zhou C, et al. Ketamine Inhibits Lipopolysaccharide Induced Astrocytes Activation by Suppressing TLR4/NF-κB. Pathway Cell Physiol Biochem 2012; 30: 609-617.

8. Aksoy Y. Antioksidan mekanizmada glutatyonun rolü. Türkiye Klinikleri Tıp Bilimleri Dergisi 2002; 22: 442-448.

9. Dogan Z, Yuzbasioglu MF, Kurutas EB, et al. Thiopental improves renal ischemia-reperfusion injury. Ren Fail 2010; 32: 391-395.

10. Fridovich I. Superoxide radical: An endogenous toxicant. Annu Rev Pharmacol Toxicol 1983; 23: 239-257.

11. Beutler E. Red cell metabolism: a manual of biochemical methods/by Ernest Beutler. 2nd ed. 1975; Grune & Stratton.

12. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1975; 95: 351-358.

13. Cortas NK, Wakid NW. Determination of Inorganic Nitrate in Serum and Urine by a Kinetic CadmiumReduction Method. Clin Chem 1990; 36: 1440-1443.

14. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265-275.

15. Yuzer H, Yuzbasioglu MF, Ciralik H, et al. Effects of Intravenöz Anesthetics on Renal Ischemia/Reperfusion Injury. Ren Fail 2009; 31: 290-296.

16. Erol B, Turker T, Tok A, et al. The protective effects of tadalafil on renal damage following ischemia reperfusion injury in rats. Kaohsiung J Med Sci 2015; 31: 454-462.

17. Ekinci-Akdamar FN, Gülçin İ, Gürsul C, Alwased SH, Bayir Y. Effect of p-coumaric acid against oxidative stress induced by cisplatin in brain tissue of rats. The J Anim Plant Sci 2017; 27: 1560- 1564.

18. Al-Eisa RA, Hamza RZ, Mehana AE, ElShenawy NS. The influence of L-carnitine on aspartame toxicity in kidney of male rats. Int J Pharmacol 2018; 14: 1118-1127.

19. Stroo I, Stokman G, Teske GJD, et al. Chemokine expression in renal ischemia/reperfusion injury is most profound during the reparative phase. Intern İmmunol 2010; 22: 433-442.

20. Tekeli AE, Yagmurdur H, Ongen E, et al. Effect of Dexketoprofen Trometamol as Immunohistochemical and Electron Microscopy on Kidney in Rats. Int J Pharmacol 2019; 15: 31-39.

21. Saricaoglu F, Dal D, Salman AE, Doral MN, Kilinç K, Aypar U. Ketamine sedation during spinal anesthesia for arthroscopic knee surgery reduced the ischemia-reperfusion injury markers. Anesth Analg 2005; 101: 904-909.

22. Ozmen MM, Zulfikaroglu B, Col C, et al. Effect of increased abdominal pressure on cytokines (IL1,IL6,TNF), C-reaktive Protein (CRP), Free radikals (NO, MDA), and histology. Surg Laparosc Endosc Percutan Tech 2009; 19: 142- 147.

23. Ergün Y, Darendeli S, Imrek S, Kilinç M, Oksüz H. Ischemia-reperfusion injury in skeletal muscle: comparison of the effects of subanesthetic doses of ketamine, propofol, and etomidate. J Surg Res 2010; 159: 1-10.

24. Chang Y, Lee JJ, Hsieh CY, Hsiao G, Chou DS, Sheu JR. Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation. Mediat Inflamm 2009: 7 pages.