The reno-protective effects of atorvastatin in crush syndrome and rhabdomyolysis:is there a dilemma?

The reno-protective effects of atorvastatin in crush syndrome and rhabdomyolysis:is there a dilemma?

Background/aim: We aim to determine the effects of low-dose atorvastatin treatment together with crush fluid resuscitation on renal functions and muscle enzyme levels in a rat model of crush syndrome. Materials and methods: The study involved female Wistar Albino rats weighing 250 300 g that were housed with free access to food and water. The crush model was obtained by compression. Rats were randomly divided into four groups: control (C) group, atorvastatin + crush fluid (ACF) group, crush fluid (CF) group, and hypertonic saline (%3) + mannitol + sodium bicarbonate (SM) group. Blood was obtained at 24, 48, and 72 h, and serum creatinine kinase, myoglobin, urea, creatinine, and lactate dehydrogenase levels were studied. Results: All parameters were statistically significantly higher in the control group than in the treatment groups at all hours. However, there was no statistically significant difference among treatment groups regarding any of the parameters. Conclusion: This is the first study determining the role of atorvastatin in the treatment of renal ischemia/reperfusion injury in a crush syndrome and rhabdomyolysis model setting. Larger studies with different atorvastatin doses are required to define the role of this drug in the treatment of renal ischemia/reperfusion injury during crush syndrome.

___

  • 1. Odeh M. The role of reperfusion-induced injury in the pathogenesis of the crush syndrome. N Engl J Med 1991; 324: 1417-1422.
  • 2. Groeneveld AB, Raijmakers PG, Rauwerda JA, Hack CE. The inflammatory response to vascular surgery-associated ischaemia and reperfusion in man: effect on postoperative pulmonary function. Eur J Vasc Endovasc Surg 1997; 14: 351- 359.
  • 3. Nishikata R, Kato N, Hiraiwa K. Oxidative stress may be involved in distant organ failure in tourniquet shock model mice. Leg Med (Tokyo) 2014; 16: 70-75.
  • 4. Gillani S,  Cao J,  Suzuki T,  Hak DJ. The effect of ischemia reperfusion injury on skeletal muscle. Injury 2012; 43: 670-675.
  • 5. Kumar VL, Guruprasad B, Wahane VD. Atorvastatin exhibits anti-inflammatory and anti-oxidant properties in adjuvantinduced monoarthritis. Inflammopharmacology 2010; 18: 303-308.
  • 6. Barbieri L, Verdoia M, Schaffer A, Nardin M, Marino P, De Luca G. The role of statins in the prevention of contrast induced nephropathy: a meta-analysis of 8 randomized trials. J Thromb Thrombolys 2014; 38: 493-502.
  • 7. Ballantyne CM, Corsini A, Davidson MH, Holdaas H, Jacobson TA, Leitersdorf E, Marz W, Reckless JP, Stein EA. Risk for myopathy with statin therapy in high-risk patients. Arch Intern Med 2003; 163: 553-564.
  • 8. Murata I, Ooi K, Sasaki H, Kimura S, Ohtake K, Ueda H, Uchida H, Yasui N, Tsutsui Y, Yoshizawa N, et al. Characterisation of systemic and histologic injury after crush syndrome and intervals of reperfusions in a small animal model. J Trauma 2011; 70: 1453-1463.
  • 9. Rajan DK, Patel NH, Valji K, Cardella JF, Brown DB, Brountzos EN, Clark TW, Grassi CJ, Meranze SG, Miller DL, et al. Quality improvement guidelines for percutaneous management of acute limb ischemia. J Vasc Interv Radiol 2009; 20: S208-218.
  • 10. Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol 2000; 11: 1553-1561.
  • 11. Sabbatini M, Pisani A, Uccello F, Serio V, Serù R, Paternò R, Cianciaruso B, Fuiano G, Andreucci M. Atorvastatin improves the course of ischemic acute renal failure in aging rats. J Am Soc Nephrol 2004; 15: 901-909.
  • 12. Todorovic Z, Nesic Z, Stojanović R, Basta-Jovanović G, Radojevic-Skodrić S, Velicković R, Chatterjee PK, Thiemermann C, Prostran M. Acute protective effects of simvastatin in the rat model of renal ischemia-reperfusion injury: it is never too late for the pretreatment. J Pharmacol Sci 2008; 107: 465-470.
  • 13. Haylor JL, Harris KP, Nicholson ML, Waller HL, Huang Q, Yang B. Atorvastatin improving renal ischemia reperfusion injury via direct inhibition of active caspase-3 in rats. Exp Biol Med 2011; 236: 755-763.
  • 14. Tucci Junior S, Molina CA, Cassini MF, Leal DM, Schineider CA, Martins AC. Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats. Acta Cir Bras 2012; 27: 477-481.
  • 15. Wu K, Lei W, Tian J, Li H. Atorvastatin treatment attenuates renal injury in an experimental model of ischemia–reperfusion in rats. BMC Nephrol 2014; 15: 14.
  • 16. Murata I,  Nozaki R,  Ooi K,  Ohtake K,  Kimura S,  Ueda H,  Nakano G,  Sonoda K,  Inoue Y,  Uchida H  et al. Nitrite reduces ischemia/reperfusion-induced muscle damage and improves survival rates in rat  crush injury  model. J Trauma Acute Care Surg 2012; 72: 1548-1554.
  • 17. Murata I,  Ooi K,  Shoji S,  Motohashi Y,  Kan M,  Ohtake K,  Kimura S,  Ueda H,  Nakano G,  Sonoda K et al. Acute lethal crush-injured rats can be successfully rescued by a single injection of high-dose dexamethasone through a pathway involving PI3K-Akt-eNOS signaling. J Trauma Acute Care Surg 2013; 75: 241-249.
  • 18. Garbaisz D, Turoczi Z, Aranyi P, Fulop A, Rosero O, Hermesz E,  Ferencz A,  Lotz G,  Harsanyi L,  Szijarto A. Attenuation of skeletal muscle and renal injury to the lower limb following  ischemia-reperfusion  using mPTP inhibitor NIM811. PLoS One 2014; 9: e101067.
  • 19. Raju Sb, Varghese K, Madhu K. Management of statin intolerance. Indian J Endocrinol Metab 2013; 17: 977-982.
  • 20. Abd TT, Jacobson TA. Statin-induced myopathy: a review and update. Expert Opin Drug Saf 2011; 10: 373-387.
  • 21. Holbrook A, Wright M, Sung M, Ribic C, Baker S. Statinassociated rhabdomyolysis: is there a dose-response relationship? Can J Cardiol 2011; 27: 146-151.