Role of leukotrienes on hepatic ischemia/reperfusion injury in rats.
BACKGROUND
Leukotrienes (LT), composed of cysteinyl LT (cLT; LTC(4), LTD(4), and LTE(4)) and LTB(4), are potent lipid mediators enhancing the vascular permeability and recruitment of neutrophils, which are common features of hepatic ischemia/reperfusion (I/R) injury. The aim of this study was to investigate whether LT can mediate the liver and lung injuries following hepatic I/R.


METHODS
Sprague-Dawley rats were subjected to 90 min of partial hepatic ischemia followed by 3, 12, and 24 h of reperfusion. In the hepatic and pulmonary tissues, LT content and the mRNA expression of LT-synthesis enzymes, 5-lypoxygenase (5-LO), LTC(4) synthase (LTC(4)-S), and LTA(4) hydrolase (LTA(4)-H) were measured. Tissue injuries were assessed by plasma ALT, histological examination, and wet-to-dry tissue weight ratios.


RESULTS
The cLT content in the hepatic tissue after 12 and 24 h reperfusion was increased 4- to 5-fold compared to controls and this was accompanied by the enhancement of hepatic edema and plasma ALT elevation. There were no significant changes in the mRNA expression of LT-synthesis enzymes in both tissues. LTB(4) levels were not increased despite a significant neutrophil infiltration in both tissues.


CONCLUSIONS
These data suggest that cLT are generated in the liver during the reperfusion period and may contribute to the development of hepatic edema and exert cytotoxicity. Factors other than LTB(4) may contribute to neutrophil infiltration.
Takamatsu
Yuji
Y
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Shimada
Kazuo
K
Chijiiwa
Kazuo
K
Kuroki
Syoji
S
Yamaguchi
Koji
K
Tanaka
Masao
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics; D003545:Cysteine / Q000378:metabolism; D004487:Edema / Q000209:etiology; D004851:Epoxide Hydrolases / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D007975:Leukotriene B4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation; D008107:Liver Diseases / Q000209:etiology; D008168:Lung / Q000378:metabolism; D008297:Male; D011654:Pulmonary Edema / Q000209:etiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology
D015289:Leukotrienes; D012333:RNA, Messenger; C112381:cysteinyl-leukotriene; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase; D005982:Glutathione Transferase; D000410:Alanine Transaminase; D004851:Epoxide Hydrolases; C041116:leukotriene-C4 synthase; D003545:Cysteine; C043134:leukotriene A4 hydrolase