Protective effects of daviditin A against endothelial damage induced by lysophosphatidylcholine.
Previous investigations have indicated that endogenous inhibitors of nitric oxide synthase (NOS) such as asymmetric dimethylarginine (ADMA) may play an important role in endothelium dysfunction, and some antioxidant drugs improve endothelium function via reduction of ADMA level. The present study examined the antioxidation and endothelial protection of daviditin A, a xanthone compound. Daviditin A significantly inhibited Cu(2+)-induced low-density lipoprotein (LDL) oxidation (EC50: 38.7 microM) and scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (EC50: 57.5 microM). Vasodilator responses to acetylcholine in rings of the isolated thoracic aorta were impaired in the presence of lysophosphatidylcholine (LPC)(5 mg/l). Daviditin A (10 or 30 microM) significantly attenuated inhibition by LPC of endothelium-dependent relaxation. Incubation of ECV304 cells with LPC (5 mg/l) for 24 h markedly elevated lactate dehydrogenase (LDH) activity and the levels of malondialdehyde (MDA) and ADMA, and decreased the content of nitric oxide (NO) and the activity of dimethylarginine dimethylaminohydrolase (DDAH). Daviditin A (1, 3 or 10 microM) significantly attenuated the increased release of LDH, increased content of MDA, and decreased level of NO induced by LPC. Daviditin A (3 or 10 microM) significantly inhibited the increased concentration of ADMA. Daviditin A (10 microM) significantly attenuated the decreased activity of DDAH. The present results suggest that daviditin A preserves endothelial dysfunction elicited by LPC, and the protective effect of daviditin A on the endothelium is related to reduction of ADMA concentration.
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #88, 410078 Changsha, Hunan, China.
De-Jian
DJ
Jiang
Jun-Lin
JL
Jiang
Gui-Shan
GS
Tan
Yan-Hua
YH
Du
Kang-Ping
KP
Xu
Yuan-Jian
YJ
Li
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008244:Lysophosphatidylcholines / Q000633:toxicity*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D029967:Swertia / Q000737:chemistry*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*
C482744:1,8-dihydroxy-3,4,7-trimethoxyxanthone; D000975:Antioxidants; D008244:Lysophosphatidylcholines; D044004:Xanthones; D009569:Nitric Oxide; D000581:Amidohydrolases; C059999:dimethylargininase