Astaxanthin Inhibits Mitochondrial Dysfunction and Interleukin-8 Expression in Helicobacter pylori-Infected Gastric Epithelial Cells.

Abstract

Helicobacter pylori (H. pylori) infection leads to gastric inflammation, peptic ulcer and gastric carcinoma. H. pylori activates NADPH oxidase and increases reactive oxygen species (ROS), which induce NF-κB activation and IL-8 expression in gastric epithelial cells. Dysfunctional mitochondria trigger inflammatory cytokine production. Peroxisome proliferator-activated receptors-γ (PPAR-γ) regulate inflammatory response. Astaxanthin is a powerful antioxidant that protects cells against oxidative stress. The present study was aimed at determining whether astaxanthin inhibits H. pylori-induced mitochondrial dysfunction, NF-κB activation, and IL-8 expression via PPAR-γ activation in gastric epithelial cells. Gastric epithelial AGS cells were treated with astaxanthin, NADPH oxidase inhibitor apocynin and PPAR-γ antagonist GW9662, and infected with H. pylori. As a result, H. pylori caused an increase in intracellular and mitochondrial ROS, NF-κB activation and IL-8 expression, but decreased mitochondrial membrane potential and ATP level. Astaxanthin inhibited H. pylori-induced alterations (increased ROS, mitochondrial dysfunction, NF-κB activation, and IL-8 expression). Astaxanthin activated PPAR-γ and its target gene catalase in H. pylori-infected cells. Apocynin reduced ROS and inhibited IL-8 expression while astaxanthin did not affect NADPH oxidase activity. Inhibitory effects of astaxanthin on ROS levels and IL-8 expression were suppressed by addition of GW9662. In conclusion, astaxanthin inhibits H. pylori-induced mitochondrial dysfunction and ROS-mediated IL-8 expression by activating PPAR-γ and catalase in gastric epithelial cells. Astaxanthin may be beneficial for preventing oxidative stress-mediated gastric inflammation-associated H. pylori infection.

• Authors: Suhn Hyung Kim, Joo Weon Lim, Hyeyoung Kim
• Journal: Nutrients (Nutrients) Vol. 10 Issue 9 (Sep 18 2018) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 30231525 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• CXCL8 protein, human
• Interleukin-8
• NF-kappa B
• PPAR gamma
• Reactive Oxygen Species
• Xanthophylls
• Adenosine Triphosphate
• astaxanthine

Topics

• Adenosine Triphosphate (metabolism)
• Antioxidants (pharmacology)
• Cell Line, Tumor
• Epithelial Cells (drug effects, metabolism, microbiology, pathology)
• Gastric Mucosa (drug effects, metabolism, microbiology, pathology)
• Gastritis (metabolism, microbiology, pathology, prevention & control)
• Helicobacter Infections (drug therapy, metabolism, microbiology, pathology)
• Helicobacter pylori (pathogenicity)
• Host-Pathogen Interactions
• Humans
• Interleukin-8 (metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism, microbiology, pathology)
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• PPAR gamma (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Xanthophylls (pharmacology)