Hepatotoxicity and endothelial dysfunction induced by high choline diet and the protective effects of phloretin in mice.
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.
Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710062, China.
Daoyuan
D
Ren
Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710062, China.
Yafei
Y
Liu
School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
Yan
Y
Zhao
Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710062, China. Electronic address: xbyang@snnu.edu.cn.
Xingbin
X
Yang
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002794:Choline / Q000008:administration & dosage*; D004032:Diet; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D011464:Epoprostenol / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000097:blood; D010693:Phloretin / Q000494:pharmacology*
D019332:Endothelin-1; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D009569:Nitric Oxide; D008315:Malondialdehyde; D011464:Epoprostenol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002794:Choline; D010693:Phloretin
Atherosclerosis; Choline; Liver injury; Phloretin; Vascular endothelial dysfunction