Display options
Cite
Abdullah-Al-Shoeb M, Sasaki K, Kikutani S, et al. The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models. Antioxidants (Basel). 2020;9(10)doi: 10.3390/antiox9100965.
Abdullah-Al-Shoeb, M., Sasaki, K., Kikutani, S., Namba, N., Ueno, K., Kondo, Y., Maeda, H., Maruyama, T., Irie, T., & Ishitsuka, Y. (2020). The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models. Antioxidants (Basel, Switzerland), 9(10), . https://doi.org/10.3390/antiox9100965
Abdullah-Al-Shoeb, Mohammad, et al. "The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models." Antioxidants (Basel, Switzerland) vol. 9,10 (2020). doi: https://doi.org/10.3390/antiox9100965
Abdullah-Al-Shoeb M, Sasaki K, Kikutani S, Namba N, Ueno K, Kondo Y, Maeda H, Maruyama T, Irie T, Ishitsuka Y. The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models. Antioxidants (Basel). 2020 Oct 09;9(10). doi: 10.3390/antiox9100965. PMID: 33050213; PMCID: PMC7601533.
Copy Download .nbib Format: NLM
Share it on

Antioxidants (Basel). 2020 Oct 09;9(10). doi: 10.3390/antiox9100965.

The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models.

Antioxidants (Basel, Switzerland)

Mohammad Abdullah-Al-Shoeb, Kenta Sasaki, Saori Kikutani, Nanami Namba, Keiichi Ueno, Yuki Kondo, Hitoshi Maeda, Toru Maruyama, Tetsumi Irie, Yoichi Ishitsuka

Affiliations

  1. Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  2. Program for Leading Graduate Schools "HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  3. Department of Biochemistry and Molecular Biology, School of Life Sciences, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh.
  4. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.

PMID: 33050213 PMCID: PMC7601533 DOI: 10.3390/antiox9100965

Abstract

An overdose of acetaminophen (APAP), the most common cause of acute liver injury, induces oxidative stress that subsequently causes mitochondrial impairment and hepatic necroptosis. N-acetyl-L-cysteine (NAC), the only recognized drug against APAP hepatotoxicity, is less effective the later it is administered. This study evaluated the protective effect of mitochondria-specific Mito-TEMPO (Mito-T) on APAP-induced acute liver injury in C57BL/6J male mice, and a three dimensional (3D)-cell culture model containing the human hepatoblastoma cell line HepG2. The administration of Mito-T (20 mg/kg, i.p.) 1 h after APAP (400 mg/kg, i.p.) injection markedly attenuated the APAP-induced elevated serum transaminase activity and hepatic necrosis. However, Mito-T treatment did not affect key factors in the development of APAP liver injury including the activation of c-jun N-terminal kinases (JNK), and expression of the transcription factor C/EBP homologous protein (CHOP) in the liver. However, Mito-T significantly reduced the APAP-induced increase in the hepatic oxidative stress marker, nitrotyrosine, and DNA fragmentation. Mito-T markedly attenuated cytotoxicity induced by APAP in the HepG2 3D-cell culture model. Moreover, liver regeneration after APAP hepatotoxicity was not affected by Mito-T, demonstrated by no changes in proliferating cell nuclear antigen formation. Therefore, Mito-T was hepatoprotective at the late-stage of APAP overdose in mice.

Keywords: CCAAT/enhancer binding protein homologous protein; ER stress; Mito-TEMPO; acetaminophen; c-jun N-terminal kinases; endoplasmic reticulum; liver injury; mitochondria

References

  1. Chem Res Toxicol. 1998 Jun;11(6):604-7 - PubMed
  2. FASEB J. 2019 Dec;33(12):13905-13919 - PubMed
  3. Drug Metab Dispos. 2002 Apr;30(4):446-51 - PubMed
  4. Oncogene. 1998 Apr 23;16(16):2141-50 - PubMed
  5. Toxicol Sci. 2017 Feb;155(2):363-378 - PubMed
  6. Transl Res. 2018 Jun;196:31-41 - PubMed
  7. Pharmacoepidemiol Drug Saf. 2011 Aug;20(8):810-8 - PubMed
  8. Free Radic Biol Med. 2008 Apr 1;44(7):1406-19 - PubMed
  9. J Biol Chem. 2008 May 16;283(20):13565-77 - PubMed
  10. J Pharmacol Exp Ther. 1990 Dec;255(3):935-41 - PubMed
  11. Chem Biol Interact. 2009 May 15;179(2-3):273-9 - PubMed
  12. Int J Biochem Cell Biol. 2018 Apr;97:98-103 - PubMed
  13. Gastroenterology. 2012 Aug;143(2):307-20 - PubMed
  14. Biomed Res Int. 2016;2016:1952947 - PubMed
  15. Arch Toxicol. 1994;68(2):110-8 - PubMed
  16. Brain Circ. 2018 Jul-Sep;4(3):84-94 - PubMed
  17. J Cell Biochem. 2017 Oct;118(10):3130-3141 - PubMed
  18. Liver Int. 2012 Jan;32(1):8-20 - PubMed
  19. Pharm Res. 2013 Sep;30(9):2174-87 - PubMed
  20. Biochim Biophys Acta Mol Basis Dis. 2020 Jan 1;1866(1):165583 - PubMed
  21. Front Pharmacol. 2019 Sep 20;10:1092 - PubMed
  22. Mutat Res. 2005 Jan 6;569(1-2):101-10 - PubMed
  23. Nature. 2014 Jan 16;505(7483):335-43 - PubMed
  24. Pharmacol Res. 2014 Sep;87:26-41 - PubMed
  25. Toxicol Appl Pharmacol. 1988 May;93(3):378-87 - PubMed
  26. Redox Biol. 2016 Dec;10:148-156 - PubMed
  27. J Hepatol. 2013 Sep;59(3):495-503 - PubMed
  28. Hepatology. 2011 Mar;53(3):974-82 - PubMed
  29. Pharmacoepidemiol Drug Saf. 2006 Jun;15(6):398-405 - PubMed
  30. Hepatology. 2015 Jan;61(1):326-36 - PubMed
  31. Toxicol Sci. 2003 Oct;75(2):458-67 - PubMed
  32. BMC Gastroenterol. 2013 Jan 30;13:21 - PubMed
  33. Hepatology. 2011 Feb;53(2):718-9 - PubMed
  34. Arch Toxicol. 2017 Feb;91(2):761-773 - PubMed
  35. J Pharmacol Sci. 2014;124(2):218-29 - PubMed
  36. Hepatology. 2011 Sep 2;54(3):969-78 - PubMed
  37. J Biol Chem. 1996 May 17;271(20):12063-7 - PubMed
  38. J Clin Invest. 2012 Apr;122(4):1574-83 - PubMed
  39. Toxicol Appl Pharmacol. 1997 Mar;143(1):1-12 - PubMed
  40. Biomaterials. 2015 Mar;45:115-23 - PubMed
  41. Pharmacol Res. 2015 Sep;99:52-62 - PubMed
  42. J Pharmacol Exp Ther. 2012 Jan;340(1):134-42 - PubMed
  43. Drug Metab Rev. 2012 Feb;44(1):88-106 - PubMed
  44. Br J Clin Pharmacol. 2011 Feb;71(2):273-82 - PubMed
  45. Toxicol Appl Pharmacol. 2014 Sep 15;279(3):266-274 - PubMed
  46. J Hepatol. 2017 Dec;67(6):1324-1331 - PubMed
  47. Med Sci Monit. 2018 Feb 28;24:1225-1231 - PubMed
  48. Clin Sci (Lond). 2018 Jan 11;132(1):111-125 - PubMed
  49. Nutr Res Pract. 2017 Apr;11(2):97-104 - PubMed
  50. Toxicol Appl Pharmacol. 2013 Jun 15;269(3):240-9 - PubMed
  51. Lancet. 2010 Jul 17;376(9736):190-201 - PubMed
  52. Drug Saf. 2005;28(3):227-40 - PubMed
  53. J Clin Invest. 1992 Jul;90(1):196-203 - PubMed
  54. Crit Care. 2012 Jan 16;16(1):R9 - PubMed
  55. Arch Intern Med. 1981 Feb 23;141(3 Spec No):380-5 - PubMed
  56. Philos Trans R Soc Lond B Biol Sci. 1985 Dec 17;311(1152):633-45 - PubMed
  57. Clin Liver Dis. 2007 Aug;11(3):525-48, vi - PubMed
  58. J Exp Med. 2012 Feb 13;209(2):307-18 - PubMed
  59. J Immunol. 2006 May 15;176(10):6245-53 - PubMed
  60. Nat Rev Drug Discov. 2018 Dec;17(12):865-886 - PubMed
  61. Toxicol Sci. 2016 Dec;154(2):214-226 - PubMed
  62. Crit Care. 2009;13(2):R55 - PubMed
  63. Pain Med. 2010 Mar;11(3):369-78 - PubMed
  64. Toxicol Sci. 2002 Jun;67(2):322-8 - PubMed
  65. Toxicol Lett. 2015 Apr 16;234(2):139-50 - PubMed
  66. Biol Pharm Bull. 2009 Jul;32(7):1215-9 - PubMed
  67. Cell Death Dis. 2013 May 09;4:e626 - PubMed
  68. Br J Clin Pharmacol. 2012 Feb;73(2):285-94 - PubMed
  69. Arch Toxicol. 2019 Jan;93(1):163-178 - PubMed

Publication Types

Grant support