Advertisement

Tacrolimus Attenuates Myocardium Damage to the Total Hepatic Ischemia-Reperfusion Via Regulation of the Mitochondrial Function

  • Yawei Chen
    Affiliations
    First Department of Comprehensive Surgery, South Building, PLA General Hospital of China, Beijing, China
    Search for articles by this author
  • Xiaohua Xie
    Correspondence
    To whom correspondence and reprint requests should be addressed at First Department of Comprehensive Surgery, South Building, PLA General Hospital of China, 28th Rd, Haidian Dis, Beijing 100853, China.
    Affiliations
    First Department of Comprehensive Surgery, South Building, PLA General Hospital of China, Beijing, China
    Search for articles by this author
Published:November 15, 2010DOI:https://doi.org/10.1016/j.jss.2010.10.013

      Background

      Ischemia and reperfusion injury to the liver remains an important clinical problem during liver transplantation and the protection of myocardial function is critical for patients suffering liver transplantation. In the present study, we evaluated the effect of tacrolimus on injured myocardium and mitochondria after total hepatic ischemia-reperfusion (THIR).

      Methods

      We utilized the THIR model to mimic the liver transplantation and evaluate the myocardial injury after THIR. Male Wistar rats were divided into four groups: control (sham operated); THIR; THIR+tacrolimus (intraperitoneally, 0.1 mg/kg), and tacrolimus alone group.

      Results

      THIR indeed damaged the myocardial and mitochondrial function, including increasing the level of MB isoenzyme of creatine kinase (CK-MB) and lactate dehydrogenase (LDH), decreasing mitochondrial transmembrane potential (MTP), mitochondrial respiratory and phosphorylating activities (P < 0.05). After administration of tacrolimus, myocardial injuries were significantly attenuated (P < 0.05).

      Conclusion

      THIR injury was associated with myocardial injury, perhaps resulting from mitochondrial function alterations. The inhibition of calcineurin and the improvement of mitochondrial respiration and antioxidant capacity maybe contributed to the protection of myocardial mitochondria function after THIR.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Surgical Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Huguet C.
        • Addario-Chieco P.
        • Gavelli A.
        • et al.
        Technique of hepatic vascular exclusion for extensive liver resection.
        Am J Surg. 1992; 163: 602
        • Chen C.F.
        • Wang D.
        • Hwang C.P.
        • et al.
        The protective effect of niacinamide on ischemia-reperfusion-induced liver injury.
        J Biomed Sci. 2001; 8: 446
        • Bhatia M.
        • Moochhala S.
        Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome.
        J Pathol. 2004; 202: 145
        • Hu S.
        • Cao W.H.
        • Sun D.
        • et al.
        [Enteral administration of carbachol on systemic inflammatory response and multiple organ dysfunction induced by partial ischemia/reperfusion injury to the gut.].
        Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2005; 17: 49
        • Tanaka N.
        [Induction mechanism of shock: Applying the etiology in judgment of the cause of death in forensic practice].
        Nihon Hoigaku Zasshi. 2004; 58: 130
        • Hogan P.G.
        • Chen L.
        • Nardone J.
        • et al.
        Transcriptional regulation by calcium, calcineurin, and NFAT.
        Genes Dev. 2003; 17: 2205
        • Wilkins B.J.
        • Molkentin J.D.
        Calcineurin and cardiac hypertrophy: Where have we been? Where are we going?.
        J Physiol. 2002; 541: 1
        • Halestrap A.P.
        Calcium, mitochondria and reperfusion injury: A pore way to die.
        Biochem Soc Trans. 2006; 34: 232
        • Leshnower B.G.
        • Kanemoto S.
        • Matsubara M.
        • et al.
        Cyclosporine preserves mitochondrial morphology after myocardial ischemia/reperfusion independent of calcineurin inhibition.
        Ann Thorac Surg. 2008; 86: 1286
        • Liu Z.H.
        • Xie X.H.
        • Ren Q.A.
        • et al.
        [Protective effect of FK 506 on the myocardial mitochondri al d amage following traumatic stress of amputation in rats.].
        Med J Chin PLA. 2009; 34: 437
        • Sunose Y.
        • Takeyoshi I.
        • Tsutsumi H.
        • et al.
        The effect of FR167653 in a canine total hepatic vascular exclusion model.
        Hepatogastroenterology. 2003; 50: 161
        • Saito S.
        • Hiroi Y.
        • Zou Y.
        • et al.
        beta-Adrenergic pathway induces apoptosis through calcineurin activation in cardiac myocytes.
        J Biol Chem. 2000; 275: 34528
        • Xiong Y.
        • Liu X.
        • Lee C.P.
        • et al.
        Attenuation of doxorubicin-induced contractile and mitochondrial dysfunction in mouse heart by cellular glutathione peroxidase.
        Free Radic Biol Med. 2006; 41: 46
        • Salvioli S.
        • Ardizzoni A.
        • Franceschi C.
        • et al.
        JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess delta psi changes in intact cells: Implications for studies on mitochondrial functionality during apoptosis.
        FEBS Lett. 1997; 411: 77
        • Zhang B.
        • Lin S.
        Effects of 3,4-dichloroaniline on testicle enzymes as biological markers in rats.
        Biomed Environ Sci. 2009; 22: 40
        • Bueno O.F.
        • Lips D.J.
        • Kaiser R.A.
        • et al.
        Calcineurin Abeta gene targeting predisposes the myocardium to acute ischemia-induced apoptosis and dysfunction.
        Circ Res. 2004; 94: 91
        • Shirane M.
        • Nakayama K.I.
        Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis.
        Nat Cell Biol. 2003; 5: 28
        • Springer J.E.
        • Azbill R.D.
        • Nottingham S.A.
        • et al.
        Calcineurin-mediated BAD dephosphorylation activates the caspase-3 apoptotic cascade in traumatic spinal cord injury.
        J Neurosci. 2000; 20: 7246
        • Almeida S.
        • Domingues A.
        • Rodrigues L.
        • et al.
        FK506 prevents mitochondrial-dependent apoptotic cell death induced by 3-nitropropionic acid in rat primary cortical cultures.
        Neurobiol Dis. 2004; 17: 435
        • Diotte N.M.
        • Xiong Y.
        • Gao J.
        • et al.
        Attenuation of doxorubicin-induced cardiac injury by mitochondrial glutaredoxin 2.
        Biochim Biophys Acta. 2009; 1793: 427
        • Mayer B.
        • Oberbauer R.
        Mitochondrial regulation of apoptosis.
        News Physiol Sci. 2003; 18: 89
        • Liu X.
        • Ren Z.
        • Zhan R.
        • et al.
        Prohibitin protects against oxidative stress-induced cell injury in cultured neonatal cardiomyocyte.
        Cell Stress Chaperones. 2009; 14: 311
        • Smaili S.S.
        • Stellato K.A.
        • Burnett P.
        • et al.
        Cyclosporin A inhibits inositol 1,4,5-trisphosphate-dependent Ca2+ signals by enhancing Ca2+ uptake into the endoplasmic reticulum and mitochondria.
        J Biol Chem. 2001; 276: 23329
        • Santana L.F.
        • Chase E.G.
        • Votaw V.S.
        • et al.
        Functional coupling of calcineurin and protein kinase A in mouse ventricular myocytes.
        J Physiol. 2002; 544: 57
        • Oyedotun K.S.
        • Lemire B.D.
        The quaternary structure of the Saccharomyces cerevisiae succinate dehydrogenase. Homology modeling, cofactor docking, and molecular dynamics simulation studies.
        J Biol Chem. 2004; 279: 9424
        • Dhar D.K.
        • Takemoto Y.
        • Nagasue N.
        • et al.
        FK506 maintains cellular calcium homeostasis in ischemia-reperfusion injury of the canine liver.
        J Surg Res. 1996; 60: 142