Role of thromboxane in producing hepatic injury during hepatic stress.
Hepatic injury after hepatic stress is caused by several mechanisms, including inflammatory reaction and microcirculatory disturbance. Levels of thromboxane, a vasoconstrictive eicosanoid, have been shown to increase in systemic circulation after different types of hepatic stress such as endotoxemia, hepatic ischemia-reperfusion, hepatectomy, liver transplantation, hemorrhagic shock and resuscitation, hepatic cirrhosis, and alcoholic liver injury. The production of thromboxane from the liver is also enhanced under these stresses, which may act on the liver in an autocrine or a paracrine fashion. Kupffer cells, resident hepatic macrophages, may be a major source of stress-induced thromboxane, although other cell types in the liver such as sinusoidal endothelial cells and hepatocytes may also produce this eicosanoid. Thromboxane induces hepatic damage through vasoconstriction, platelet aggregation, induction of leukocyte adhesion, up-regulation of proinflammatory cytokines, and induction of other vasoconstrictor release. In this regard, administration of cyclooxygenase inhibitor, specific thromboxane synthase inhibitor, and specific thromboxane receptor antagonists has been shown to protect from severe hepatic injury elicited by these hepatic stresses. Furthermore, blockade of Kupffer cell function by administration of gadolinium chloride showed salutary effects in preventing hepatic damage in bile duct ligation models. This review article summarizes the recent knowledge of the role of thromboxane in various types of hepatic stress and the effects of thromboxane inhibitors in these models.
Yokoyama
Yukihiro
Y
Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Nimura
Yuji
Y
Nagino
Masato
M
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000818:Animals; D015415:Biomarkers; D018450:Disease Progression; D005260:Female; D006801:Humans; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects*; D008099:Liver / Q000293:injuries / Q000473:pathology*; D008102:Liver Circulation / Q000502:physiology; D008107:Liver Diseases / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D011379:Prognosis; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013931:Thromboxanes / Q000032:analysis / Q000096:biosynthesis*
D015415:Biomarkers; D017482:Receptors, Thromboxane; D013931:Thromboxanes