Open Access

PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells

  • Authors:
    • In‑Hye Kim
    • Jeong‑Wook Choi
    • Taek‑Jeong Nam
  • View Affiliations

  • Published online on: December 9, 2019     https://doi.org/10.3892/etm.2019.8304
  • Pages: 849-860
  • Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acetaminophen (APAP) is a widely used analgesic and antipyretic. It is safe at normal treatment doses; however, APAP overdose is a major cause of acute liver and kidney failure. A variety of methods to reduce the damage caused by APAP overdose have previously been evaluated. The protein‑rich seaweed Pyropia yezoensis has antioxidant, antitumor and anti‑inflammatory activities, and protects against cytotoxicity. However, little is known regarding the protective effects of P. yezoensis peptide against APAP‑induced hepatotoxicity. The present study investigated the ability of P. yezoensis peptide (PYP1‑4) to ameliorate the damage caused by APAP‑induced hepatotoxicity using HepG2 as the model cell line in addition to the signaling pathways involved. Briefly, cell viability, nitric oxide, reactive oxygen species and apoptosis assays were performed in conjunction with western blot analysis and reverse transcription‑quantitative PCR. First, the present study revealed the minimum toxic concentration of APAP (15 mM) and the resting concentration of PYP1‑4 (0‑500 ng/ml). Administration of PYP1‑4 to APAP‑induced cells decreased the nitric oxide and reactive oxygen species levels, and restored the levels of antioxidant‑associated proteins (catalase, heme oxygenase 1, superoxide dismutase 2 and quinone oxidoreductase 1). PYP1‑4 increased the translocation of nuclear factor, erythroid 2 like 2 to the nucleus and the activities of glycogen synthase kinase‑3β, Akt and AMP‑activated protein kinase. In addition, APAP induced apoptosis; however, PYP1‑4 inhibited apoptosis by modulating the levels of pro‑apoptotic markers (Bad), anti‑apoptotic markers (Bcl‑2 and BH3 interacting domain death agonist), caspases and poly (ADP‑ribose) polymerase 1. Subsequently, the insulin‑like growth factor 1 receptor signaling pathway was investigated to determine whether PYP1‑4 treatment restored the levels of cell growth‑associated factors during APAP‑induced hepatotoxicity. PYP1‑4 treatment impacted the levels of components of the insulin receptor substrate 1/PI3K/Akt and Ras/Raf/ERK signaling pathways, and promoted cell survival. Therefore, the P. yezoensis peptide PYP1‑4 may be useful for preventing APAP‑induced hepatotoxicity.
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February-2020
Volume 19 Issue 2

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Spandidos Publications style
Kim IH, Choi JW and Nam TJ: PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells. Exp Ther Med 19: 849-860, 2020.
APA
Kim, I., Choi, J., & Nam, T. (2020). PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells. Experimental and Therapeutic Medicine, 19, 849-860. https://doi.org/10.3892/etm.2019.8304
MLA
Kim, I., Choi, J., Nam, T."PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells". Experimental and Therapeutic Medicine 19.2 (2020): 849-860.
Chicago
Kim, I., Choi, J., Nam, T."PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells". Experimental and Therapeutic Medicine 19, no. 2 (2020): 849-860. https://doi.org/10.3892/etm.2019.8304