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Mahmoud AM, Al Dera HS. 18β-Glycyrrhetinic acid exerts protective effects against cyclophosphamide-induced hepatotoxicity: potential role of PPARγ and Nrf2 upregulation. Genes Nutr. 2015;10(6):41doi: 10.1007/s12263-015-0491-1.
Mahmoud, A. M., & Al Dera, H. S. (2015). 18β-Glycyrrhetinic acid exerts protective effects against cyclophosphamide-induced hepatotoxicity: potential role of PPARγ and Nrf2 upregulation. Genes & nutrition, 10(6), 41. https://doi.org/10.1007/s12263-015-0491-1
Mahmoud, Ayman M, and Al Dera, Hussein S. "18β-Glycyrrhetinic acid exerts protective effects against cyclophosphamide-induced hepatotoxicity: potential role of PPARγ and Nrf2 upregulation." Genes & nutrition vol. 10,6 (2015): 41. doi: https://doi.org/10.1007/s12263-015-0491-1
Mahmoud AM, Al Dera HS. 18β-Glycyrrhetinic acid exerts protective effects against cyclophosphamide-induced hepatotoxicity: potential role of PPARγ and Nrf2 upregulation. Genes Nutr. 2015 Nov;10(6):41. doi: 10.1007/s12263-015-0491-1. Epub 2015 Sep 19. PMID: 26386843; PMCID: PMC4575654.
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Genes Nutr. 2015 Nov;10(6):41. doi: 10.1007/s12263-015-0491-1. Epub 2015 Sep 19.

18β-Glycyrrhetinic acid exerts protective effects against cyclophosphamide-induced hepatotoxicity: potential role of PPARγ and Nrf2 upregulation.

Genes & nutrition

Ayman M Mahmoud, Hussein S Al Dera

Affiliations

  1. Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni Suef, 62514, Egypt. [email protected].
  2. Basic Medical Sciences Department, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

PMID: 26386843 PMCID: PMC4575654 DOI: 10.1007/s12263-015-0491-1

Abstract

18β-Glycyrrhetinic acid (18β-GA) has been proposed as a promising hepatoprotective agent. The current study aimed to investigate the protective action and the possible mechanisms of 18β-GA against cyclophosphamide (CP)-induced liver injury in rats, focusing on the role of peroxisome proliferator-activated receptor gamma (PPARγ) and NF-E2-related factor-2 (Nrf2). Rats were administered 18β-GA at doses 25 and 50 mg/kg 2 weeks prior to CP injection. Five days after CP administration, animals were sacrificed and samples were collected. CP induced hepatic damage evidenced by the histopathological changes and significant increase in serum pro-inflammatory cytokines, liver marker enzymes, and liver lipid peroxidation and nitric oxide (NO) levels. 18β-GA counteracted CP-induced oxidative stress and inflammation as assessed by restoration of the antioxidant defenses and diminishing of pro-inflammatory cytokines, lipid peroxidation, and NO production. These hepatoprotective effects appear to depend on activation of Nrf2 and PPARγ, and subsequent suppression of nuclear factor-kappa B. In conclusion, the present study provides evidence that 18β-GA exerts hepatoprotective effects against CP through induction of antioxidant defenses and suppression of inflammatory response. This report also confers new information that 18β-GA protects liver against the toxic effect of chemotherapeutic alkylating agents via activation of Nrf2 and PPARγ.

Keywords: Chemotherapy; Hepatotoxicity; Inflammation; Nrf2; PPARs

References

  1. Mol Nutr Food Res. 2006 Nov;50(11):1087-8 - PubMed
  2. Free Radic Biol Med. 2008 Jun 1;44(11):1897-911 - PubMed
  3. Bioorg Med Chem. 2009 Apr 1;17(7):2785-92 - PubMed
  4. J Lab Clin Med. 1963 May;61:882-8 - PubMed
  5. Oxid Med Cell Longev. 2009 Sep-Oct;2(4):207-13 - PubMed
  6. Food Chem Toxicol. 2010 Aug-Sep;48(8-9):2326-36 - PubMed
  7. J Biol Chem. 2002 Jan 18;277(3):2330-5 - PubMed
  8. J Neurophysiol. 2008 Jan;99(1):49-59 - PubMed
  9. Oncogene. 2006 Oct 30;25(51):6868-86 - PubMed
  10. Methods. 2001 Dec;25(4):402-8 - PubMed
  11. Clin Chim Acta. 1974 May 31;53(1):109-15 - PubMed
  12. Hypertension. 2000 Sep;36(3):430-5 - PubMed
  13. Clin Rev Allergy Immunol. 2009 Feb;36(1):4-12 - PubMed
  14. Anal Biochem. 1970 Mar;34:30-8 - PubMed
  15. J Biol Chem. 2005 Jun 17;280(24):22925-36 - PubMed
  16. Scand J Gastroenterol. 2009;44(3):358-65 - PubMed
  17. South Med J. 2006 Dec;99(12 ):1399-400 - PubMed
  18. Chem Biol Interact. 2002 Jan 22;139(1):79-95 - PubMed
  19. Int J Biol Macromol. 2011 Nov 1;49(4):801-5 - PubMed
  20. J Agric Food Chem. 2011 Jul 27;59(14):7726-33 - PubMed
  21. Oxid Med Cell Longev. 2013;2013:763257 - PubMed
  22. Can J Physiol Pharmacol. 2014 Sep;92 (9):717-24 - PubMed
  23. Gastroenterology. 2003 Dec;125(6):1834-44 - PubMed
  24. J Am Coll Nutr. 1998 Apr;17(2):116-23 - PubMed
  25. Exp Mol Pathol. 2011 Feb;90(1):123-30 - PubMed
  26. Nefrologia. 2011;31(4):496-8 - PubMed
  27. FASEB J. 2002 Aug;16(10 ):1227-36 - PubMed
  28. Cell Signal. 2012 Mar;24(3):596-605 - PubMed
  29. Biochem Pharmacol. 2000 Jan 1;59(1):13-23 - PubMed
  30. Arch Pharm Res. 2008 Jun;31(6):794-7 - PubMed
  31. Mediators Inflamm. 2009;2009:137072 - PubMed
  32. Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2046-51 - PubMed
  33. PLoS One. 2013;8(1):e53662 - PubMed
  34. Diabetes. 2006 Mar;55(3):622-32 - PubMed
  35. Food Chem Toxicol. 2007 Sep;45(9):1551-7 - PubMed
  36. Nature. 2005 Sep 29;437(7059):759-63 - PubMed
  37. Biochem Pharmacol. 1997 Jan 24;53(2):121-33 - PubMed
  38. Free Radic Res. 2011 Nov;45(11-12):1245-66 - PubMed
  39. Chem Biol Interact. 2009 Aug 14;180(3):398-406 - PubMed
  40. J Clin Chem Clin Biochem. 1976 Sep;14(9):421-7 - PubMed
  41. J Clin Invest. 2006 Mar;116(3):590-7 - PubMed
  42. Am J Transplant. 2007 Sep;7(9):2064-74 - PubMed
  43. Eur J Biochem. 1974 Sep 16;47(3):469-74 - PubMed
  44. Biochem Biophys Res Commun. 2008 Feb 15;366(3):698-704 - PubMed
  45. Clin Chim Acta. 2003 Jan;327(1-2):69-79 - PubMed
  46. Biochem Soc Symp. 2004;(71):157-76 - PubMed
  47. Food Chem Toxicol. 2008 Nov;46(11):3368-74 - PubMed
  48. Food Chem Toxicol. 2008 Apr;46(4):1279-87 - PubMed
  49. Acta Clin Belg. 2011 Sep-Oct;66(5):337-45 - PubMed
  50. PPAR Res. 2008;2008:134059 - PubMed
  51. J Clin Oncol. 2005 Oct 1;23(28):6908-18 - PubMed
  52. J Physiol Pharmacol. 2005 Sep;56(3):337-53 - PubMed
  53. FASEB J. 2005 Jul;19(9):1061-6 - PubMed
  54. J Pharm Biomed Anal. 2011 Feb 20;54(3):535-44 - PubMed
  55. Hum Exp Toxicol. 2015 Jun;34(6):628-41 - PubMed
  56. Br J Cancer. 2006 May 8;94(9):1226-30 - PubMed
  57. Hypertension. 2004 Jan;43(1):48-56 - PubMed
  58. PPAR Res. 2012;2012:757803 - PubMed
  59. Annu Rev Pharmacol Toxicol. 2007;47:89-116 - PubMed
  60. Am J Respir Crit Care Med. 2010 Jul 15;182(2):170-82 - PubMed
  61. Cancer. 2007 Jun 1;109(11):2291-8 - PubMed
  62. J Clin Pathol. 2004 Apr;57(4):350-4 - PubMed
  63. Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):385-94 - PubMed
  64. Drugs. 1991 Nov;42(5):781-95 - PubMed
  65. Handb Exp Pharmacol. 2010;(196 ):233-66 - PubMed
  66. Acta Pharmacol Sin. 2010 Nov;31(11):1421-30 - PubMed
  67. Nature. 2004 Sep 23;431(7007):461-6 - PubMed
  68. Arch Physiol Biochem. 2007 Oct-Dec;113(4-5):234-58 - PubMed
  69. Annu Rev Med. 2002;53:409-35 - PubMed
  70. J Cancer Res Clin Oncol. 2014 Jul;140(7):1103-9 - PubMed
  71. World J Gastroenterol. 2010 Jun 7;16(21):2657-63 - PubMed
  72. Mol Endocrinol. 2002 Dec;16(12):2793-801 - PubMed
  73. Mol Med. 2001 Feb;7(2):135-45 - PubMed

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