Hepatotoxicity and endothelial dysfunction induced by high choline diet and the protective effects of phloretin in mice.

Abstract

The involvement of choline and its metabolite trimethylamine-N-oxide (TMAO) in endothelial dysfunction and atherosclerosis has been repeatedly confirmed. Phloretin, a dihydrochalcone flavonoid usually present in apples, possesses a variety of biological activities including vascular nutrition. This study was designed to investigate whether phloretin could alleviate or prevent high choline-induced vascular endothelial dysfunction and liver injury in mice. Mice were provided with 3% high choline water and given phloretin orally daily for 10 weeks. The high choline-treated mice showed the significant dyslipidemia and hyperglycemia with the impaired liver and vascular endothelium (p < 0.01). Administration of phloretin at 200 and 400 mg/kg bw significantly reduced the choline-induced elevation of serum TC, TG, LDL-C, AST, ALT, ET-1 and TXA2 (p < 0.01), and markedly antagonized the choline-induced decrease of serum PGI2, HDL-C and NO levels. Furthermore, phloretin elevated hepatic SOD and GSH-Px activities and decreased hepatic MDA levels of the mice exposed to high choline water. Moreover, histopathological test with the H&E and Oil Red O staining of liver sections confirmed the high choline diet-caused liver steatosis and the hepatoprotective effect of phloretin. These findings suggest that high choline causes oxidative damage, and phloretin alleviate vascular endothelial dysfunction and liver injury.

• Authors: Daoyuan Ren, Yafei Liu, Yan Zhao, Xingbin Yang
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 94 Pg. 203-12 (Aug 2016) ISSN: 1873-6351 [Electronic] England
• PMID: 27316781 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Endothelin-1
• Fatty Acids, Nonesterified
• Lipids
• Nitric Oxide
• Malondialdehyde
• Epoprostenol
• Aspartate Aminotransferases
• Alanine Transaminase
• Choline
• Phloretin

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Body Weight (drug effects)
• Choline (administration & dosage)
• Diet
• Endothelin-1 (blood)
• Endothelium, Vascular (drug effects, pathology, physiopathology)
• Epoprostenol (blood)
• Fatty Acids, Nonesterified (metabolism)
• Lipids (blood)
• Liver (drug effects, metabolism, physiopathology)
• Male
• Malondialdehyde (metabolism)
• Mice
• Nitric Oxide (blood)
• Phloretin (pharmacology)