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Int J Mol Sci. 2018 Aug 29;19(9). pii: E2563. doi: 10.3390/ijms19092563.

Effects of Antioxidants in Reducing Accumulation of Fat in Hepatocyte.

Author information

1
Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul 03080, Korea. fellnim@naver.com.
2
Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul 03080, Korea. charisma4395@naver.com.
3
Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul 03080, Korea. stopsh23@naver.com.
4
Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul 03080, Korea. 0949kim@hanmail.net.
5
Department of Neurosurgery, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul 07061, Korea. nslee@snu.ac.kr.
6
Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul 03080, Korea. ehshin@snu.ac.kr.
7
Seoul National University Bundang Hospital, Seongnam 13620, Korea. ehshin@snu.ac.kr.

Abstract

The progress of the hepatic steatosis (HS), a clinicopathological status, is influenced by cellular oxidative stress, lipogenesis, fatty acid (FA) oxidation, and inflammatory responses. Because antioxidants are gaining attention as potent preventive agents for HS, we aimed to investigate anti-lipogenic effects of the antioxidants vitamin C (VC), N-acetylcysteine (NAC), and astaxanthin (ATX) using hepatocytes. For this, we established an in vitro model using 1 mM oleic acid (OA) and human liver hepatocellular carcinoma (HepG2) cells; 10 μM antioxidants were evaluated for their ability to reduce fat accumulation in hepatocytes. Our results showed that all three antioxidants were effective to reduce fat accumulation for the molecular targets such as reduction in lipid droplets, triglyceride (TG) concentration, reactive oxygen species (ROS) production, and cell apoptosis, as well as in gene expressions of endoplasmic reticulum (ER) stress-related effectors, lipogenesis, and inflammatory cytokines. There were simultaneous increases in diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect, cell survival, AMPK phosphorylation, NRF2-related gene expression for cellular defense, and FA β-oxidation. However, among these, ATX more effectively inhibited ER stress and lipogenesis at the intracellular level than VC or NAC. Consequently, ATX was also more effective in inhibiting cell death, lipotoxicity, and inflammation. Our result emphasizes that ATX achieved greater lipotoxicity reduction than VC and NAC.

KEYWORDS:

N-acetyl-l-cysteine; astaxanthin; free radical scavenging; lipogenesis; oleic acid; vitamin C

PMID:
30158441
PMCID:
PMC6164327
DOI:
10.3390/ijms19092563
[Indexed for MEDLINE]
Free PMC Article

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