The Protective Effect of Humanin Derivative AGA(C8R)-HNG17 Against Acetaminophen-Induced Liver Injury in Mice

David Meridor, Aviv Cohen, Boris Khalfin, Lakshminarasaiah Uppalapati, Roni Kasher, Ilana Nathan, Abraham H. Parola

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Until recently, necrotic cells death was considered an uncontrolled process. However, evidence was recently presented that necrosis is a regulated process associated with many clinical conditions. Humanin and its derivatives are peptides known for their anti-apoptotic activity against Alzheimer’s disease. Recently, the humanin-derivative AGA(C8R)-HNG17 (PAGASRLLLLTGEIDLP) was found to have protective effect against necrosis in traumatic brain injury model in mice. We have demonstrated now the protective effect of AGA(C8R)-HNG17 against necrosis in a dose dependent manner in HepG2 cells in vitro, where necrosis was induced in a glucose-free medium by chemohypoxia. Moreover, it was further demonstrated in a model of acetaminophen-induced liver injury in C57BL/6J male mice, in vivo. Intraperitoneal administration of the peptide at 10 and 30 mg/kg significantly prevented the increase in two plasma markers for necrosis, alanine aminotransferase (ALT, EC 2.6.1.2) and aspartate aminotransferase (AST, EC 2.6.1.1). Mitochondrial dysfunction is known to be the main cause of hepatic failure. Hence, the protection from liver injury by AGA(C8R)-HNG17, which we have recently found to target the mitochondria, may be mediated by mitochondrial regulation. Currently, there is no effective treatment for liver diseases, in which necrosis is involved. These findings may provide a new anti-necrotic strategy against APAP-induced liver injury and other liver diseases associated with necrosis using AGA(C8R)-HNG17 as a therapeutic agent.

Original languageEnglish
Pages (from-to)565-571
Number of pages7
JournalInternational Journal of Peptide Research and Therapeutics
Volume25
Issue number2
DOIs
StatePublished - 1 Jun 2019

Keywords

  • Acetaminophen
  • Hepatotoxicity
  • Humanin
  • Liver
  • Necrosis

ASJC Scopus subject areas

  • Analytical Chemistry
  • Bioengineering
  • Biochemistry
  • Molecular Medicine
  • Drug Discovery

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