Potential of 3,4-dihydroxy-phenyl lactic acid for ameliorating ischemia-reperfusion-induced microvascular disturbance in rat mesentery.
This study intended to examine the effect of 3,4-dihydroxy-phenyl lactic acid (DLA), a major ingredient of Salvia miltiorrhiza, on ischemia-reperfusion (I/R)-induced rat mesenteric microcirculatory injury. DLA (5 mg.kg(-1).h(-1)), superoxide dismutase (SOD, 12,000 U.kg(-1).h(-1)), or catalase (CAT, 20 mg/kg) was continuously infused either starting from 10 min before the ischemia or 10 min after the initiation of reperfusion. The venule diameter, number of adherent leukocytes, FITC-albumin leakage, dihydrorhodamine 123 fluorescence, and mast cell degranulation were determined using an intravital microscope. The production of hydrogen peroxide (H(2)O(2)) and the expression of adhesion molecules CD11b/CD18 in neutrophils were evaluated by in vitro experiments. The results showed that pretreatment with DLA significantly reduced peroxide production in and leukocyte adhesion to venular wall, albumin leakage, and mast cell degranulation induced by I/R. The DLA posttreatment exerted an ameliorating effect on I/R-induced disorders as well, characterized by inhibiting further increase in peroxide production in venular wall and albumin leakage and diminishing the number of leukocytes that had adhered to the venular wall. In vitro experiments revealed that treatment with DLA significantly attenuated TNF-alpha plus fMLP-evoked production of H(2)O(2) and the H(2)O(2)-elicited expression of CD11b/CD18 on neutrophils. SOD and CAT manifested similarly but with the exception that either SOD or CAT were unable to retrieve the adherent leukocytes if administrated after initiation of reperfusion and to depress the H(2)O(2)-induced expression of CD11b/CD18 on neutrophils. It is concluded that DLA protects from and ameliorates the I/R-induced microcirculatory disturbance by interfering with both peroxide production and adhesion molecule expression.
Han
Jing-Yan
JY
Dept. of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking Univ., 38 Xueyuan Rd., Beijing 100083, People's Republic of China. hanjingyan@bjmu.edu.cn
Horie
Yoshinori
Y
Fan
Jing-Yu
JY
Sun
Kai
K
Guo
Jun
J
Miura
Soichiro
S
Hibi
Toshifumi
T
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002374:Catalase / Q000008:administration & dosage; D002448:Cell Adhesion / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000378:metabolism; D007262:Infusions, Intravenous; D007773:Lactates / Q000008:administration & dosage / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D008643:Mesentery / Q000098:blood supply*; D008833:Microcirculation / Q000187:drug effects*; D018715:Microscopy, Video; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000008:administration & dosage; D013997:Time Factors; D014699:Venules / Q000187:drug effects / Q000503:physiopathology
D000975:Antioxidants; D039481:CD11b Antigen; D018821:CD18 Antigens; D007773:Lactates; C035055:3,4-dihydroxyphenyllactic acid; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase