Exposure to tert-butyl hydroperoxide (t-BHP) leads to cytotoxicity and oxidative stress in various organs and cell types. The bioactive peptides extracted from Oysters exhibit marked antioxidant activity. The impacts of Crassostrea gigas peptides on t-BHP-triggered oxidative stress remain largely unknown. The protective and antioxidant activity of a C.gigas peptide, PEP-1, on t-BHP-treated HepG2 cells, was investigated. PEP-1, this peptide is arginine kinase in oysters. This enzyme functions as a catalyst for the chemical reaction and serves as a phosphate transferase. Since it was the most expressed protein in the adductor muscle of oysters. Our determination showed the lowest level of a toxic concentration of t-BHP (200 µM) and the resting concentration of PEP-1 (0-1000 ng/ml). PEP-1 exerted a protective effect against t-BHP-induced apoptosis by modifying the expression of pro-and anti-apoptotic proteins. PEP-1 administration reduced nitric oxide and ROS levels while restoring levels of antioxidant proteins in t-BHP-induced cells. PEP-1 exhibited the capacity to enhance the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Therefore, the C. gigas peptide PEP-1 has demonstrated its ability to protect HepG2 cells against oxidative stress induced by t-BHP.
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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.
Copyright: © Kim et al.