Mitochondrial impairment induced by chenodeoxycholic acid: The protective effect of taurine and carnosine supplementation

Document Type : Research(Original) Article

Authors

Shiraz University of Medical Sciences, Pharmaceutical Sciences Research Center

Abstract

The cholestatic liver disease ensues with a hepatic accumulation of cytotoxic molecules. Several hydrophobic bile acids are known as cytotoxic agents accumulated in the liver during cholestasis. Chenodeoxycholic acid (CDCA) is a toxic hydrophobic bile acid. Oxidative stress and mitochondrial dysfunction are well-known mechanisms of bile acids cytotoxicity. In the current study, CDCA effect on isolated liver mitochondria was monitored by analyzing the changes in mitochondrial dehydrogenases activity, mitochondrial permeabilization, and mitochondrial membrane potential. On the other hand, taurine (1 mM) and carnosine (1 mM) were added as potential protective agents against CDCA-induced mitochondrial dysfunction. Increasing concentrations of CDCA (100 µM - 1000 µM) impaired mitochondrial membrane potential, decreased mitochondrial dehydrogenases activity and enhanced mitochondrial permeabilization and swelling. It was found that taurine and carnosine supplementation preserved mitochondrial function in the presence of CDCA. The results mention that toxicologically relevant concentrations of CDCA impaired mitochondrial function. On the other hand, taurine and carnosine might be applicable as protective agents against bile acids-induced mitochondrial impairment and toxicity.

References

  1. Lefkowitch J. 6 Cholestasis. Liver Pathology. 2011;4;89.
  2. Gossard AA, Talwalkar JA. Cholestatic liver disease. The Medical clinics of North America. 2014;98;73-85.
  3. Patil A, Mayo MJ. Complications of Cholestasis. In: Md KDL, Md JAT, editors. Cholestatic Liver Disease. Clinical Gastroenterology: Humana Press; 2008. p. 155-169.
  4. Perez MJ, Briz O. Bile-acid-induced cell injury and protection. W J Gastroenterol. 2009;15;1677-1689.
  5. Martinez-Diez MC, Serrano MA, Monte MJ, Marin JJG. Comparison of the effects of bile acids on cell viability and DNA synthesis by rat hepatocytes in primary culture. Biochim Biophys Acta. 2000;1500;153-160.
  6. Heidari R, Niknahad H, Sadeghi A, Mohammadi H, Ghanbarinejad V, Ommati MM, Hosseini A, Azarpira N, Khodaei F, Farshad O, Rashidi E, Siavashpour A, Najibi A, Ahmadi A, Jamshidzadeh A. Betaine treatment protects liver through regulating mitochondrial function and counteracting oxidative stress in acute and chronic animal models of hepatic injury. Biomed Pharmacother. 2018;103;75-86.
  7. Heidari R, Moezi L, Asadi B, Ommati MM, Azarpira N. Hepatoprotective effect of boldine in a bile duct ligated rat model of cholestasis/cirrhosis. PharmaNutrition. 2017;5;109-117.
  8. Heidari R, Ghanbarinejad V, Mohammadi H, Ahmadi A, Esfandiari A, Azarpira N, Niknahad H. Dithiothreitol supplementation mitigates hepatic and renal injury in bile duct ligated mice: Potential application in the treatment of cholestasis-associated complications. Biomed Pharmacother. 2018;99;1022-1032.
  9. Heidari R, Ghanbarinejad V, Mohammadi H, Ahmadi A, Ommati MM, Abdoli N, Aghaei F, Esfandiari A, Azarpira N, Niknahad H. Mitochondria protection as a mechanism underlying the hepatoprotective effects of glycine in cholestatic mice. Biomed Pharmacother. 2018;97;1086-1095.
  10. Bomzon A, Holt S, Moore K. Bile acids, oxidative stress, and renal function in biliary obstruction. Semin Nephrol. 1997;17;549-562.
  11. Chen C-C, Ho C-Y, Chaung H-C, Tain Y-L, Hsieh C-S, Kuo F-Y, Yang C-Y, Huang L-T. Fish omega-3 fatty acids induce liver fibrosis in the treatment of bile duct-ligated rats. Dig Dis Sci. 2013;58;440-447.
  12. Copple BL, Jaeschke H, Klaassen CD. Oxidative stress and the pathogenesis of cholestasis. Semin Liver Dis. 2010;30;195-204.
  13. Holt S, Marley R, Fernando B, Harry D, Anand R, Goodier D, Moore K. Acute cholestasis-induced renal failure: effects of antioxidants and ligands for the thromboxane A2 receptor. Kidney Int. 1999;55;271-277.
  14. Rolo AP, Oliveira PJ, Moreno AJM, Palmeira CM. Bile acids affect liver mitochondrial bioenergetics: possible relevance for cholestasis therapy. Toxicol Sci. 2000;57;177-185.
  15. Spivey JR, Bronk SF, Gores GJ. Glycochenodeoxycholate-induced lethal hepatocellular injury in rat hepatocytes. Role of ATP depletion and cytosolic free calcium. J Clin Invest. 1993;92;17-24.
  16. Schulz S, Schmitt S, Wimmer R, Aichler M, Eisenhofer S, Lichtmannegger J, Eberhagen C, Artmann R, Tookos F, Walch A, Krappmann D, Brenner C, Rust C, Zischka H. Progressive stages of mitochondrial destruction caused by cell toxic bile salts. Biochim Biophys Acta. 2013;1828;2121-2133.
  17. Arduini A, Serviddio G, Tormos AM, Monsalve M, Sastre J. Mitochondrial dysfunction in cholestatic liver diseases. Front Biosci. 2012;4;2233-2252.
  18. Rolo AP, Palmeira CM, Wallace KB. Mitochondrially mediated synergistic cell killing by bile acids. Biochim Biophys Acta. 2003;1637;127-132.
  19. Palmeira CM, Rolo AP. Mitochondrially-mediated toxicity of bile acids. Toxicology. 2004;203;1-15.
  20. Huxtable RJ. Physiological actions of taurine. Physiol Rev. 1992;72;101-163.
  21. Huxtable RJ, Michalk D. Taurine in Health and Disease: Springer Science & Business Media; 2013 2013/11/21/. 447 p.
  22. Timbrell JA, Seabra V, Waterfield CJ. The in vivo and in vitro protective properties of taurine. General Pharmacol. 1995;26;453-462.
  23. Heidari R, Jamshidzadeh A, Ghanbarinejad V, Ommati MM, Niknahad H. Taurine supplementation abates cirrhosis-associated locomotor dysfunction. Clin Exp Hepatol. 2018;4;72-82.
  24. Niknahad H, Jamshidzadeh A, Heidari R, Zarei M, Ommati MM. Ammonia-induced mitochondrial dysfunction and energy metabolism disturbances in isolated brain and liver mitochondria, and the effect of taurine administration: relevance to hepatic encephalopathy treatment. Clin Exp Hepatol. 2017;3;141-151.
  25. Jamshidzadeh A, Abdoli N, Niknahad H, Azarpira N, Mardani E, Mousavi S, Abasvali M, Heidari R. taurine alleviates brain tissue markers of oxidative stress in a rat model of hepatic encephalopathy. Trend Pharm Sci. 2017;3;181-192.
  26. Jamshidzadeh A, Heidari R, Abasvali M, Zarei M, Ommati MM, Abdoli N, Khodaei F, Yeganeh Y, Jafari F, Zarei A, Latifpour Z, Mardani E, Azarpira N, Asadi B, Najibi A. Taurine treatment preserves brain and liver mitochondrial function in a rat model of fulminant hepatic failure and hyperammonemia. Biomed Pharmacother. 2017;86;514-520.
  27. Heidari R, Jamshidzadeh A, Niknahad H, Safari F, Azizi H, Abdoli N, Ommati MM, Khodaei F, Saeedi A, Najibi A. The hepatoprotection provided by taurine and glycine against antineoplastic drugs induced liver injury in an ex vivo model of normothermic recirculating isolated perfused rat liver. Trend Pharm Sci. 2016;2;59-76.
  28. Heidari R, Jamshidzadeh A, Niknahad H, Mardani E, Ommati MM, Azarpira N, Khodaei F, Zarei A, Ayarzadeh M, Mousavi S, Abdoli N, Yeganeh BS, Saeedi A, Najibi A. Effect of taurine on chronic and acute liver injury: Focus on blood and brain ammonia. Toxicol Report. 2016;3;870-879.
  29. Heidari R, Rasti M, Shirazi Yeganeh B, Niknahad H, Saeedi A, Najibi A. Sulfasalazine-induced renal and hepatic injury in rats and the protective role of taurine. BioImpacts. 2016;6;3-8.
  30. Heidari R, Sadeghi N, Azarpira N, Niknahad H. Sulfasalazine-induced hepatic injury in an ex vivo model of isolated perfused rat liver and the protective role of taurine. Pharm Sci. 2015;21;211-219.
  31. Heidari R, Jamshidzadeh A, Keshavarz N, Azarpira N. Mitigation of Methimazole-Induced Hepatic Injury by Taurine in Mice. Sci Pharm. 2015;83;143-158.
  32. Heidari R, Babaei H, Eghbal MA. Amodiaquine-induced toxicity in isolated rat hepatocytes and the cytoprotective effects of taurine and/or N-acetyl cysteine. Res Pharm Sci. 2014;9;97-105.
  33. Heidari R, Babaei H, Eghbal MA. Cytoprotective Effects of Taurine Against Toxicity Induced by Isoniazid and Hydrazine in Isolated Rat Hepatocytes. Arch Industl Hyg Toxicol. 2013;64;201-210.
  34. Hansen SH, Andersen ML, Cornett C, Gradinaru R, Grunnet N. A role for taurine in mitochondrial function. J Biomed Sci. 2010;17;1-8.
  35. Hansen SH, Grunnet N. Taurine, Glutathione and Bioenergetics. In: Idrissi AE, L'Amoreaux WJ, editors. Taurine 8. Advances in Experimental Medicine and Biology: Springer New York; 2013. p. 3-12.
  36. Ahmadian E, Babaei H, Mohajjel Nayebi A, Eftekhari A, Eghbal MA. Venlafaxine-induced cytotoxicity towards isolated rat hepatocytes involves oxidative stress and mitochondrial/lysosomal dysfunction. Adv Pharm Bull. 2016;6;521-530.
  37. Parvez S, Tabassum H, Banerjee BD, Raisuddin S. Taurine Prevents Tamoxifen-Induced Mitochondrial Oxidative Damage in Mice. Basic Clin Pharmacol Toxicol. 2008;102;382-387.
  38. Xu S, He M, Zhong M, Li L, Lu Y, Zhang Y, Zhang L, Yu Z, Zhou Z. The neuroprotective effects of taurine against nickel by reducing oxidative stress and maintaining mitochondrial function in cortical neurons. Neurosci Lett. 2015;590;52-57.
  39. Zhang Z, Liu D, Yi B, Liao Z, Tang L, Yin D, He M. Taurine supplementation reduces oxidative stress and protects the liver in an iron-overload murine model. Mol Med Report. 2014;10;2255-2262.
  40. Boldyrev AA, Aldini G, Derave W. Physiology and Pathophysiology of Carnosine. Physiol Rev. 2013;93;1803-1845.
  41. Cheng J, Wang F, Yu D-F, Wu P-F, Chen J-G. The cytotoxic mechanism of malondialdehyde and protective effect of carnosine via protein cross-linking/mitochondrial dysfunction/reactive oxygen species/MAPK pathway in neurons. Eur J Pharmacol. 2011;650;184-194.
  42. Fouad AA, El-Rehany MA-A, Maghraby HK. The hepatoprotective effect of carnosine against ischemia/reperfusion liver injury in rats. Eur J Pharmacol. 2007;572;61-68.
  43. Fouad AA, Morsy MA, Gomaa W. Protective effect of carnosine against cisplatin-induced nephrotoxicity in mice. Environ Toxicol Pharmacol. 2008;25;292-297.
  44. Kurata H, Fujii T, Tsutsui H, Katayama T, Ohkita M, Takaoka M, Tsuruoka N, Kiso Y, Ohno Y, Fujisawa Y, Shokoji T, Nishiyama A, Abe Y, Matsumura Y. Renoprotective effects of l-carnosine on ischemia/reperfusion-induced renal injury in rats. J Pharmacol Exp Ther. 2006;319;640-647.
  45. Lee Y-t, Hsu C-c, Lin M-h, Liu K-s, Yin M-c. Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Eur J Pharmacol. 2005;513;145-150.
  46. Guiotto A, Calderan A, Ruzza P, Borin G. Carnosine and carnosine-related antioxidants: A Review. Curr Med Chem. 2005;12;2293-2315.
  47. Heidari R, Niknahad H, Jamshidzadeh A, Azarpira N, Bazyari M, Najibi A. Carbonyl traps as potential protective agents against methimazole-induced liver injury. J Biochem Mol Toxicol. 2015;29;173-181.
  48. Jamshidzadeh A, Heidari R, Latifpour Z, Ommati MM, Abdoli N, Mousavi S, Azarpira N, Zarei A, Zarei M, Asadi B, Abasvali M, Yeganeh Y, Jafari F, Saeedi A, Najibi A, Mardani E. Carnosine ameliorates liver fibrosis and hyperammonemia in cirrhotic rats. Clin Res Hepatol Gastroenterol. 2017;41;424-434.
  49. Jamshidzadeh A, Abdoli N, Niknahad H, Azarpira N, Mousavi S, Mardani E, Abasvali M, Heidari R. Carnosine supplementation mitigates brain tissue markers of oxidative stress in a rat model of fulminant hepatic failure. Trend Pharm Sci. 2017;3;149-160.
  50. Akram J, Reza H, Farzaneh A, Maral R, Forouzan K, Mohammad Mehdi O, Maryam A, Roya F, Arastoo S, Negar A, Asma N. Antimalarial drugs-induced hepatic injury in rats and the protective role of carnosine. Pharm Sci. 2016;22;170-180.
  51. Jamshidzadeh A, Niknahad H, Heidari R, Zarei M, Ommati MM, Khodaei F. Carnosine protects brain mitochondria under hyperammonemic conditions: Relevance to hepatic encephalopathy treatment. PharmaNutrition. 2017;5;58-63.
  52. Corona C, Frazzini V, Silvestri E, Lattanzio R, La Sorda R, Piantelli M, Canzoniero LMT, Ciavardelli D, Rizzarelli E, Sensi SL. Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg-AD mice. PLoS One. 2011;6;e17971.
  53. Hipkiss AR. Aging, proteotoxicity, mitochondria, glycation, NAD+ and carnosine: possible inter-relationships and resolution of the oxygen paradox. Front Aging Neurosci. 2010;2.
  54. Caro AA, Adlong LW, Crocker SJ, Gardner MW, Luikart EF, Gron LU. Effect of garlic-derived organosulfur compounds on mitochondrial function and integrity in isolated mouse liver mitochondria. Toxicol Lett. 2012;214;166-174.
  55. Niknahad H, Heidari R, Mohammadzadeh R, Ommati MM, Khodaei F, Azarpira N, Abdoli N, Zarei M, Asadi B, Rasti M, Yeganeh BS, Taheri V, Saeedi A, Najibi A. Sulfasalazine induces mitochondrial dysfunction and renal injury. Ren Fail. 2017;39;745-753.
  56. Akram J, Hossein N, Reza H, Maryam A, Forouzan K, Mohammad Reza A, Omid F. Propylthiouracil-induced mitochondrial dysfunction in liver and its relevance to drug-induced hepatotoxicity. 2017;23;95-102.
  57. Zhao P, Kalhorn TF, Slattery JT. Selective mitochondrial glutathione depletion by ethanol enhances acetaminophen toxicity in rat liver. Hepatology. 2002;36;326-335.
  58. Niknahad H, Jamshidzadeh A, Heidari R, Hosseini Z, Mobini K, Khodaei F, Ommati MM, Abdoli N, Keshavarz N, Bazyari M, Najibi A. Paradoxical effect of methimazole on liver mitochondria: In vitro and in vivo. Toxicol Lett. 2016;259;108-115.
  59. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65;55-63.
  60. Niknahad H, Heidari R, Alzuhairi AM, Najibi A. Mitochondrial dysfunction as a mechanism for pioglitazone-induced injury toward HepG2 cell line. Pharm Sci. 2015;20;169-174.
  61. Ommati MM, Tanideh N, Rezakhaniha B, Wang J, Sabouri S, Vahedi M, Dormanesh B, Koohi Hosseinabadi O, Rahmanifar F, Moosapour S, Akhlaghi A, Heidari R, Zamiri MJ. Is immunosuppression, induced by neonatal thymectomy, compatible with poor reproductive performance in adult male rats? Andrology. 2018;6;199-213.
  62. Heidari R, Jafari F, Khodaei F, Shirazi Yeganeh B, Niknahad H. Mechanism of valproic acid‐induced Fanconi syndrome involves mitochondrial dysfunction and oxidative stress in rat kidney. Nephrology. 2018;23;351-361.
  63. Niknahad H, Jamshidzadeh A, Heidari R, Abdoli N, Mehdi M, Ommati FJ, Zarei M, Asadi B. The postulated hepatotoxic metabolite of methimazole causes mitochondrial dysfunction and energy metabolism disturbances in liver. Pharm Sci. 2016;22;217-226.
  64. Heidari R, Babaei H, Eghbal M. Mechanisms of methimazole cytotoxicity in isolated rat hepatocytes. Drug Chem Toxicol. 2013;36;403-411.
  65. Ahmadian E, Eftekhari A, Fard JK, Babaei H, Nayebi AM, Mohammadnejad D, Eghbal MA. In vitro and in vivo evaluation of the mechanisms of citalopram-induced hepatotoxicity. Arch Pharmacal Res. 2017;40;1296-1313.
  66. Eftekhari A, Ahmadian E, Panahi-Azar V, Hosseini H, Tabibiazar M, Dizaj SM. Hepatoprotective and free radical scavenging actions of quercetin nanoparticles on aflatoxin B1-induced liver damage: in vitro/in vivo studies. Artificial Cell Nanomed Biotechnol. 2018;46;411-420.
  67. Heidari R, Babaei H, Eghbal MA. Cytoprotective effects of organosulfur compounds against methimazole-induced toxicity in isolated rat hepatocytes. Adv Pharm Bull. 2013;3;135-142.
  68. Ommati MM, Heidari R, Jamshidzadeh A, Zamiri MJ, Sun Z, Sabouri S, Wang J, Ahmadi F, Javanmard N, Seifi K, Mousapour S, Yeganeh BS. Dual effects of sulfasalazine on rat sperm characteristics, spermatogenesis, and steroidogenesis in two experimental models. Toxicol Lett. 2018;284;46-55.
  69. Rodriguez-Garay EA. Cholestasis: human disease and experimental animal models. Ann Hepatol. 2003;2;150-158.
  70. Pessayre D, Fromenty B, Berson A, Robin M-A, Letteron P, Moreau R, Mansouri A. Central role of mitochondria in drug-induced liver injury. Drug Metab Rev. 2012;44;34-87.
  71. Pessayre D, Fromenty B, Mansouri A, Berson A. Hepatotoxicity due to mitochondrial injury. Drug-induced liver disease. 2002;49-84.
  72. Hansen SH, Andersen ML, Birkedal H, Cornett C, Wibrand F. The important role of taurine in oxidative metabolism. Adv Exp Med Biol. 2006;583;129-135.
  73. Jong CJ, Azuma J, Schaffer S. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids. 2012;42;2223-2232.
  74. Schaffer SW, Azuma J, Mozaffari M. Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol. 2009;87;91-99.
  75. Suzuki T, Suzuki T, Wada T, Saigo K, Watanabe K. Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases. EMBO J. 2002;21;6581-6589.
  76. Shao A, Hathcock JN. Risk assessment for the amino acids taurine, l-glutamine and l-arginine. Regul Toxicol Pharmacol. 2008;50;376-399.
  77. Yamori Y, Taguchi T, Hamada A, Kunimasa K, Mori H, Mori M. Taurine in health and diseases: consistent evidence from experimental and epidemiological studies. J Biomed Sci. 2010;17;S6.
  78. Aldini G, Facino RM, Beretta G, Carini M. Carnosine and related dipeptides as quenchers of reactive carbonyl species: from structural studies to therapeutic perspectives. BioFactors. 2005;24;77-87.
  79. Zhang Z-y, Sun B-l, Yang M-f, Li D-w, Fang J, Zhang S. Carnosine attenuates early brain injury through its antioxidative and anti-apoptotic effects in a rat experimental subarachnoid hemorrhage model. Cell Mol Neurobiol. 2015;35;147-157.
  80. Hipkiss AR. Chapter 3 Carnosine and Its Possible Roles in Nutrition and Health. In: Research BTAiF, Nutrition, editors. 57: Academic Press; 2009. p. 87-154.
  81. Ommati MM, Jamshidzadeh A, Heidari R, Sun Z, Zamiri MJ, Khodaei F, Mousapour S, Ahmadi F, Javanmard N, Yeganeh BS. Carnosine and histidine supplementation blunt lead-induced reproductive toxicity through antioxidative and mitochondria-dependent mechanisms. Biol Trace Elem Res. 2018;In Press;1-12.
  82. Heidari R, Ghanbarinejad V, Ommati MM, Jamshidzadeh A, Niknahad H. Regulation of mitochondrial function and energy metabolism: A primary mechanism of cytoprotection provided by carnosine. Trend Pharm Sci. 2018;4;41-50.

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