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Hepatoprotective effects of lactic acid-fermented garlic extract against acetaminophen-induced acute liver injury in rats

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Abstract

The aim of the present study was to investigate the protective effect of fermented garlic extract by lactic acid bacteria (LAFGE) against acetaminophen (AAP)-induced acute liver injury in rats. Here we demonstrated that rats treated with LAFGE exhibit resistance to AAP-induced liver injury accompanied by lowered plasma alanine amino transferase levels and decreased proinflammatory responses. This function of LAFGE is linked to its capacity of suppressing AAP-induced apoptosis in the liver, partly via the inhibition of MAPK phosphorylation as well as down-regulation of p53. Our findings reveal that LAFGE modulates the signaling pathways involved in hepatic apoptosis through cellular redox control, as indicated by the inhibition of lipid peroxidation, glutathione and ATP depletion, and the elevation of antioxidant enzyme activities. Taken together, these findings indicate that LAFGE ameliorates AAP-induced liver injury by preventing oxidative stress-mediated apoptosis, thereby establishing LAFGE as a potential supplement in the treatment of AAP-induced liver injury.

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References

  1. Agarwal R, Hennings L, Rafferty TM, Letzig LG, McCullough S, James LP, Mac Millan-Crow LA, Hinson JA. Acetaminophen-induced hepatotoxicity and protein nitration in neuronal nitric-oxide synthase knockout mice. J. Pharmacol. Exp. Ther. 340: 134–142 (2012)

    Article  CAS  Google Scholar 

  2. Slitt AM, Dominick PK, Roberts JC, Cohen SD. Effect of ribose cysteine pretreatment on hepatic and renal acetaminophen metabolite formation and glutathione depletion. Basic Clin. Pharmacol. 96: 487–494 (2005)

    Article  CAS  Google Scholar 

  3. Hu JJ, Yoo JS, Lin M, Wang EJ, Yang CS. Protective effects of diallyl sulfide on acetaminophen-induced toxicities. Food Chem. Toxicol. 34: 963–969 (1996)

    Article  CAS  Google Scholar 

  4. Hinson JA, Reid AB, McCullough SS, James LP. Acetaminophen-induced hepatotoxicity: role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transition. Drug Metab. Rev. 36: 805–822 (2004)

    Article  CAS  Google Scholar 

  5. Kim HK, Kwak JH, Kim KH. Physiological activity and antioxidative effect of garlic (Allium sativum L.) extract. Food Sci. Biotechnol. 11: 500–506 (2002)

    Google Scholar 

  6. Tsubura A, Lai YC, Kuwata M, Uehara N, Yoshizawa K. Anticancer effects of garlic and garlic-derived compounds for breast cancer control. Anti-Cancer Agent. Me. 11: 249–253 (2011)

    Article  CAS  Google Scholar 

  7. Keiss HP, Dirsch VM, Hartung T, Haffner T, Trueman L, Auger J, Kahane R, Vollm ar AM. G arlic ( Allium sativum L.) m odulates c ytokine expression i n lipopolysaccharide-activated human blood thereby inhibiting NF-kappaB activity. J. Nutr. 133: 2171–2175 (2003)

    CAS  Google Scholar 

  8. Colin-Gonzalez AL, Santana RA, Silva-Islas CA, Chanez-Cardenas ME, Santamaria A, Maldonado PD. The antioxidant mechanisms underlying the aged garlic extract-and S-allylcysteine-induced protection. Oxid. Med. Cell. Longev. 2012: 907162 (2012)

    Article  Google Scholar 

  9. Kim YS, Baek HH, Chung IM, Kwon B, Ji GE. Garlic fermentation by lactic acid bacteria. Food Sci. Biotechnol. 18: 1279–1283 (2009)

    CAS  Google Scholar 

  10. Leroy F, De Vuyst L. Lactic acid bacteria as functional starter cultures for the food fermentation industry. Trends Food Sci. Tech. 15: 67–78 (2004)

    Article  CAS  Google Scholar 

  11. Feldberg RS, Chang SC, Kotik AN, Nadler M, Neuwirth Z, Sundstrom DC, Thompson NH. In vitro mechanism of inhibition of bacterial cell growth by allicin. Antimicrob. Agents Ch. 32: 1763–1768 (1988)

    Article  CAS  Google Scholar 

  12. Raghunandana Rao R, Srinivasa Rao S, Venkataraman PR. Investigations on plant antibiotics; Studies on allicin, the antibacterial principle of Allium sativum (garlic). J. Sci. Ind. Res. India 5: 31–35 (1946)

    CAS  Google Scholar 

  13. Cavallito CJ, Bailey JH. Allicin, the antibacterial principle of Allium sativum. I. Isolation, physical properties and antibacterial action. J. Am. Chem. Soc. 66: 1950–1951 (1944)

    Article  CAS  Google Scholar 

  14. Jung EB, Choi JH, Yu HJ, Kim KH, Lee SG, Hwang YI, Lee SH. Organosulfur compounds in fermented garlic extracts and the effects on alcohol induced cytotoxicity in CYP2E1-transfected HepG2 cells. J. Korean Soc. Food Sci. Nutr. 42: 342–347 (2013)

    Article  CAS  Google Scholar 

  15. Sies H, Akerboom TP. Glutathione disulfide (GSSG) efflux from cells and tissues. Method Enzymol. 105: 445–451 (1984)

    Article  CAS  Google Scholar 

  16. Fraga CG, Leibovitz BE, Tappel AL. Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: Characterization and comparison with homogenates and microsomes. Free Radical Bio. Med. 4: 155–161 (1988)

    Article  CAS  Google Scholar 

  17. Amacher DE. Serum transaminase elevations as indicators of hepatic injury following the administration of drugs. Regul. Toxicol. Pharm. 27: 119–130 (1998)

    Article  CAS  Google Scholar 

  18. Gabriel LP, Michel C. Detection and Evaluation of Chemically Induced Liver Injury. Principles and Methods of Toxicology. 5th ed. CRC Press, Boca Raton, FL, USA. pp. 1465–1507 (2007)

    Google Scholar 

  19. Raucy JL, Lasker JM, Lieber CS, Black M. Acetaminophen activation by human liver cytochromes P450IIE1 and P450IA2. Arch. Biochem. Biophys. 271: 270–283 (1989)

    Article  CAS  Google Scholar 

  20. Aldaba-Muruato LR, Moreno MG, Shibayama M, Tsutsumi V, Muriel P. Protective effects of allopurinol against acute liver damage and cirrhosis induced by carbon tetrachloride: Modulation of NF-kappaB, cytokine production and oxidative stress. Biochim. Biophys. Acta. 1820: 65–75 (2012)

    Article  CAS  Google Scholar 

  21. McGill MR, Sharpe MR, Williams CD, Taha M, Curry SC, Jaeschke H. The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. J. Clin. Invest. 122: 1574–1583 (2012)

    Article  CAS  Google Scholar 

  22. Jaeschke H, Bajt ML. Intracellular signaling mechanisms of acetaminopheninduced liver cell death. Toxicol. Sci. 89: 31–41 (2006)

    Article  CAS  Google Scholar 

  23. El-Hassan H, Anwar K, Macanas-Pirard P, Crabtree M, Johnson, VL, Lee PC, Hinton RH, Price SC, Kass GE. Involvement of mitochondria in acetaminopheninduced apoptosis and hepatic injury: Roles of cytochrome c, Bax, Bid, and caspases. Toxicol. Appl. Pharm. 191: 118–129 (2003)

    Article  CAS  Google Scholar 

  24. Kakkar P, Singh BK. Mitochondria: A hub of redox activities and cellular distress control. Mol. Cell. Biochem. 305: 235–253(2007)

    Article  CAS  Google Scholar 

  25. Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ. Proapoptotic BAX and BAK: A requisite gateway to mitochondrial dysfunction and death. Science 292: 727–730 (2001)

    Article  CAS  Google Scholar 

  26. Lee SS, Buters JT, Pineau T, Fernandez-Salguero P, Gonzalez FJ. Role of CYP2E1 in the hepatotoxicity of acetaminophen. J. Biol. Chem. 271: 12063–12067 (1996)

    Article  CAS  Google Scholar 

  27. Zhao X, Cong X, Zheng L, Xu L, Yun L, Peng J. Dioscin, a natural steroid saponin, shows remarkable protective effect against acetaminophen-induced liver damage in vitro and in vivo. Toxicol. Lett. 214: 69–80 (2012)

    Article  CAS  Google Scholar 

  28. Schafer T, Scheuer C, Roemer K, Menger MD, Vollmar B. Inhibition of p53 protects liver tissue against endotoxin-induced apoptotic and necrotic cell death. FASEB J. 17: 660–667 (2003)

    Article  CAS  Google Scholar 

  29. Nakagawa H, Maeda S. Molecular mechanisms of liver injury and hepatocarcinogenesis: Focusing on the role of stress-activated MAPK. Patholog. Res. Int. 2012: 172894 (2012)

    Google Scholar 

  30. Win S, Than TA, Han D, Petrovic LM, Kaplowitz N. c-Jun N-terminal kinase (JNK)-dependent acute liver injury from acetaminophen or tumor necrosis factor (TNF) requires mitochondrial Sab protein expression in mice. J. Biol. Chem. 286: 35071–35078 (2011)

    Article  CAS  Google Scholar 

  31. Nakagawa H, Maeda S, Hikiba Y, Ohmae T, Shibata W, Yanai A, Sakamoto K, Ogura K, Noguchi T, Karin M, Ichijo H, Omata M. Deletion of apoptosis signalregulating kinase 1 attenuates acetaminophen-induced liver injury by inhibiting c-Jun N-terminal kinase activation. Gastroenterology 135: 1311–1321 (2008)

    Article  CAS  Google Scholar 

  32. Jaeschke H, McGill MR, Williams CD, Ramachandran A. Current issues with acetaminophen hepatotoxicity—A clinically relevant model to test the efficacy of natural products. Life Sci. 88: 737–745 (2011)

    Article  CAS  Google Scholar 

  33. Sener G, Toklu HZ, Sehirli AO, Velioglu-Ogunc A, Cetinel S, Gedik N. Protective effects of resveratrol against acetaminophen-induced toxicity in mice. Hepatol. Res. 35: 62–68 (2006)

    Article  CAS  Google Scholar 

  34. Masubuchi Y, Suda C, Horie T. Involvement of mitochondrial permeability transition in acetaminophen-induced liver injury in mice. J. Hepatol. 42: 110–116 (2005)

    Article  CAS  Google Scholar 

  35. Hsu CC, Lin CC, Liao TS, Yin MC. Protective effect of s-allyl cysteine and spropyl cysteine on acetaminophen-induced hepatotoxicity in mice. Food Chem. Toxicol. 44: 393–397 (2006)

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. R&D center, Bioland, Ansan, Gyeonggi, 24606, Korea

    Sung Jin Lee, Seung Hyun Lee & Heui Jong Yu

  2. Deptartment of Food and Biotechnology, Korea University, Sejong, 30019, Korea

    Hee Seop Lee, Won Chul Lim, Jin Hyup Lee & Hong Yon Cho

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  1. Hee Seop Lee
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  2. Won Chul Lim
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  3. Sung Jin Lee
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  4. Seung Hyun Lee
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  6. Jin Hyup Lee
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  7. Hong Yon Cho
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Correspondence to Hong Yon Cho.

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Lee, H.S., Lim, W.C., Lee, S.J. et al. Hepatoprotective effects of lactic acid-fermented garlic extract against acetaminophen-induced acute liver injury in rats. Food Sci Biotechnol 25, 867–873 (2016). https://doi.org/10.1007/s10068-016-0143-2

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  • DOI: https://doi.org/10.1007/s10068-016-0143-2

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