Inhibition of inflammation and oxidative stress by an imidazopyridine derivative X22 prevents heart injury from obesity.

Abstract

Inflammation and oxidative stress plays an important role in the development of obesity-related complications and cardiovascular disease. Benzimidazole and imidazopyridine compounds are a class of compounds with a variety of activities, including anti-inflammatory, antioxidant and anti-cancer. X22 is an imidazopyridine derivative we synthesized and evaluated previously for anti-inflammatory activity in lipopolysaccharide-stimulated macrophages. However, its ability to alleviate obesity-induced heart injury via its anti-inflammatory actions was unclear. This study was designed to evaluate the cardioprotective effects of X22 using cell culture studies and a high-fat diet rat model. We observed that palmitic acid treatment in cardiac-derived H9c2 cells induced a significant increase in reactive oxygen species, inflammation, apoptosis, fibrosis and hypertrophy. All of these changes were inhibited by treatment with X22. Furthermore, oral administration of X22 suppressed high-fat diet-induced oxidative stress, inflammation, apoptosis, hypertrophy and fibrosis in rat heart tissues and decreased serum lipid concentration. We also found that the anti-inflammatory and anti-oxidative actions of X22 were associated with Nrf2 activation and nuclear factor-kappaB (NF-κB) inhibition, respectively, both in vitro and in vivo. The results of this study indicate that X22 may be a promising cardioprotective agent and that Nrf2 and NF-κB may be important therapeutic targets for obesity-related complications.

• Authors: Yuanyuan Qian, Yali Zhang, Peng Zhong, Kesong Peng, Zheng Xu, Xuemei Chen, Kongqin Lu, Gaozhi Chen, Xiaokun Li, Guang Liang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 20 Issue 8 Pg. 1427-42 (08 2016) ISSN: 1582-4934 [Electronic] England
• PMID: 27019072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Blood Glucose
• Imidazoles
• Lipids
• NF-kappa B
• Pyridines
• Reactive Oxygen Species
• X22 compound
• Palmitic Acid

Topics

• Animals
• Apoptosis (drug effects)
• Blood Glucose (metabolism)
• Cardiomegaly (metabolism, pathology)
• Cell Line
• Diet, High-Fat
• Fibrosis
• Heart Injuries (complications, drug therapy, pathology, prevention & control)
• Imidazoles (administration & dosage, chemistry, pharmacology, therapeutic use)
• Inflammation (complications, drug therapy)
• Lipids (blood)
• Male
• Myocardium (pathology)
• NF-kappa B (metabolism)
• Obesity (blood, complications, pathology)
• Oxidative Stress (drug effects)
• Palmitic Acid
• Pyridines (administration & dosage, chemistry, pharmacology, therapeutic use)
• Rats, Wistar
• Reactive Oxygen Species (metabolism)