Open Access

Anti‑apoptotic effects of human placental hydrolysate against hepatocyte toxicity in vivo and in vitro

  • Authors:
    • Dong‑Ho Bak
    • Jungtae Na
    • Mi Ji Choi
    • Byung Chul Lee
    • Chang Taek Oh
    • Jeom‑Yong Kim
    • Hae Jung Han
    • Moo Joong Kim
    • Tae Ho Kim
    • Beom Joon Kim
  • View Affiliations

  • Published online on: August 17, 2018     https://doi.org/10.3892/ijmm.2018.3830
  • Pages: 2569-2583
  • Copyright: © Bak et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Apoptosis and oxidative stress are essential for the pathogenesis of acute liver failure and fulminant hepatic failure. Human placental hydrolysate (hPH) has been reported to possess antioxidant and anti‑inflammatory properties. In the present study, the protective effects of hPH against D‑galactosamine (D‑GalN)‑ and lipopolysaccharide (LPS)‑induced hepatocyte apoptosis were investigated in vivo. In addition, the molecular mechanisms underlying the anti‑apoptotic activities of hPH against D‑GalN‑induced cell death in vitro were examined. Male Sprague‑Dawley rats were injected with D‑GaIN/LPS with or without the administration of hPH. Rats were sacrificed 24 h after D‑GaIN/LPS intraperitoneal injection, and the blood and liver samples were collected for future inflammation and hepatotoxicity analyses. Changes in cell viability, apoptosis protein expression, mitochondrial mass, mitochondrial membrane potential, reactive oxygen species generation, and the levels of proteins and mRNA associated with a protective mechanism were determined in HepG2 cells pretreated with hPH for 2 h prior to D‑GalN exposure. The findings suggested that hPH treatment effectively protected against D‑GalN/LPS‑induced hepatocyte apoptosis by reducing the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, interleukin‑6, and tumor necrosis factor‑α, and increasing the level of proliferating cell nuclear antigen. It was also found that hPH inhibited the apoptotic cell death induced by D‑GalN. hPH activated the expression of antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, and catalase, which were further upregulated by the Kelch‑like ECH2‑associated protein 1‑p62‑nuclear factor‑erythroid 2‑related factor 2 pathway, a component of oxidative stress defense mechanisms. Furthermore, hPH markedly reduced cytosolic and mitochondrial reactive oxygen species and rescued mitochondrial loss and dysfunction through the reduction of damage‑regulated autophagy modulator, p53, and C/EBP homologous protein. Collectively, hPH exhibited a protective role in hepatocyte apoptosis by inhibiting oxidative stress and maintaining cell homeostasis. The underlying mechanisms may be associated with the inhibition of endoplasmic reticulum stress and minimization of the autophagy progress.
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November-2018
Volume 42 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Bak DH, Na J, Choi MJ, Lee BC, Oh CT, Kim JY, Han HJ, Kim MJ, Kim TH, Kim BJ, Kim BJ, et al: Anti‑apoptotic effects of human placental hydrolysate against hepatocyte toxicity in vivo and in vitro. Int J Mol Med 42: 2569-2583, 2018.
APA
Bak, D., Na, J., Choi, M.J., Lee, B.C., Oh, C.T., Kim, J. ... Kim, B.J. (2018). Anti‑apoptotic effects of human placental hydrolysate against hepatocyte toxicity in vivo and in vitro. International Journal of Molecular Medicine, 42, 2569-2583. https://doi.org/10.3892/ijmm.2018.3830
MLA
Bak, D., Na, J., Choi, M. J., Lee, B. C., Oh, C. T., Kim, J., Han, H. J., Kim, M. J., Kim, T. H., Kim, B. J."Anti‑apoptotic effects of human placental hydrolysate against hepatocyte toxicity in vivo and in vitro". International Journal of Molecular Medicine 42.5 (2018): 2569-2583.
Chicago
Bak, D., Na, J., Choi, M. J., Lee, B. C., Oh, C. T., Kim, J., Han, H. J., Kim, M. J., Kim, T. H., Kim, B. J."Anti‑apoptotic effects of human placental hydrolysate against hepatocyte toxicity in vivo and in vitro". International Journal of Molecular Medicine 42, no. 5 (2018): 2569-2583. https://doi.org/10.3892/ijmm.2018.3830