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The mechanism of cytotoxicity of 4‐nonylphenol in a human hepatic cell line involves ER‐stress, apoptosis, and mitochondrial dysfunction
Author(s) -
Paolella Gaetana,
Romanelli Antonio M.,
Martucciello Stefania,
Sposito Silvia,
Lepretti Marilena,
Esposito Carla,
Capaldo Anna,
Caputo Ivana
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22780
Subject(s) - nonylphenol , apoptosis , oxidative stress , xbp1 , microbiology and biotechnology , chemistry , ingestion , mitochondrion , cell culture , cytotoxicity , programmed cell death , biology , biochemistry , environmental chemistry , genetics , gene , rna , rna splicing , in vitro
4‐Nonylphenol (4‐NP) is an emerging environmental pollutant widely diffused in waters and sediments. It mainly derives from the degradation of alkyl phenol ethoxylates, compounds commonly employed as industrial surfactants. 4‐NP strongly contaminates foods and waters for human use; thus, it displays a wide range of toxic effects not only for aquatic organisms but also for mammals and humans. After ingestion through the diet, it tends to accumulate in body fluids and tissues. One of the main organs where 4‐NP and its metabolites are concentrated is the liver, where it causes, even at low doses, oxidative stress and apoptosis. In the present study, we analyzed the effects of 4‐NP on a human hepatic cell line (HepG2) to deepen the knowledge of its cytotoxic mechanism. We found that 4‐NP, in a range of concentration from 50 to 100 μM, significantly reduced cell viability; it caused a partial block of proliferation and induced apoptosis with activation of caspase‐3 and overexpression of p53. Moreover, 4‐NP induced‐apoptosis seemed to involve both an ER‐stress response, with the appearance of high level of GRP78, CHOP and the spliced XBP1, and a dysregulation of mitochondrial physiology, characterized by an overexpression of main markers of mitochondrial dynamics. Our data support the idea that a daily consumption of 4‐NP‐contaminated foods may lead to local damages at the level of gastrointestinal system, including liver, with negative consequences for the organ physiology.