Herbal cardiotonic pills prevent gut ischemia/reperfusion-induced hepatic microvascular dysfunction in rats fed ethanol chronically.
OBJECTIVE
Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaertn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/reperfusion (I/R) in rats fed ethanol chronically.


METHODS
Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-alpha and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia.


RESULTS
In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-alpha and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption.


CONCLUSIONS
These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-alpha production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.
Horie
Yoshinori
Y
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. yhorie@sc.itc.keio.ac.jp
Han
Jing-Yan
JY
Mori
Shuka
S
Konishi
Masahiro
M
Kajihara
Mikio
M
Kaneko
Takehiko
T
Yamagishi
Yoshiyuki
Y
Kato
Shinzo
S
Ishii
Hiromasa
H
Hibi
Toshifumi
T
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology; D007422:Intestines / Q000098:blood supply; D018921:Leukostasis / Q000188:drug therapy; D008099:Liver / Q000098:blood supply / Q000187:drug effects; D008108:Liver Diseases, Alcoholic / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008833:Microcirculation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*
D002492:Central Nervous System Depressants; D004365:Drugs, Chinese Herbal; D000431:Ethanol