The role of thromboxane A2 [TxA2] in liver injury in mice

Anti-thromboxane B2 antibodies protect against acetaminophen-induced liver injury in mice

“…Supporting this assertion, several studies have shown that a decrease in TXA 2 synthesis by inhibition of TX-synthase or COX-2 has beneficial effect on liver injury induced by various toxic agents other than APAP, some of which are not dependent on hepatic drug metabolism. 21,22,32,37,38 The presented results indicate that TXA 2 plays an important role in the onset and development of APAP-induced liver injury in mice. Among the eicosanoids, TXA 2 promotes inflammatory processes in the liver, has vasoconstrictive effect in the portal venous system and induces leukocyte adhesion in the sinusoids, all of which lead to hepatic tissue injury.…”

“…ane (TX) synthase inhibitors, and ONO-3708, a thromboxane receptor (TPR) antagonist, highly ameliorated liver injury in the abovementioned models of toxic hepatitis. 21,22,25 However, data from the study of Guarner et al suggest that TXA 2 inhibition per se does not reduce hepatic necrosis induced by APAP. 25 Therefore, selective inhibition of the TX synthase may, besides decreasing synthesis of TXA 2 , increase production of PGI 2 or PGE 2 , the protective effects of which have been demonstrated in various models of liver injury.…”

“…into mice, caused clear elevation of serum ALT and AST levels and enhanced the histopathological score of liver necrosis. 21 We are not able to offer an appropriate explanation for the biological inefficacy of U-46619, except that a different mice strain was used in our experiments. Our results clearly show that BZI, a selective inhibitor of TX synthase, when given to mice 2 h after APAP significantly improved the survival and decreased plasma ALT level of treated animals.…”

“…[25][26][27][28][29] The elevated levels of TXB 2 have been found in liver and systemic circulation after hepatic injury was induced by different agents, such are endotoxemia, hepatic ischemia-reperfusion, hepatectomy, liver transplantation, hepatic cirrhosis, ethanol and CCl 4 . 21,23,[31][32][33] Due to the unstabile nature and very short half-life of TXA 2 , its stabile metabolite, TXB 2 , was used in our investigations. Although TXB 2 is considered to be a biologically inactive metabolite of TXA 2 , it has been shown that TXB 2 has several biological activities such as increasing pulmonary airway, pulmonary arterial and systemic arterial pressure in dogs, increasing or decreasing myocardial contractility on isolated rat heart and increasing the rate of apoptosis in cultured rat hepatocytes.…”

“…19,20 Thus, it was shown that the production of TXA 2 by liver homogenates ex vivo is significantly elevated in liver injury induced with carbon tetrachloride (CCl 4 ), lipopolysaccharide (LPS) or ethanol. [21][22][23] Similarly, the overproduction of endogenous TXA 2 has been found to be involved in APAPinduced liver damage. 24,25 Administration of OKY-046 or OKY-1581, a selective thrombox-Contributions: IĆ, substantial contributions to conception and design of the study, conduction of all experiments, drafting the article; acquisition, analysis and interpretation of data, writing of the manuscript and final approval of the version to be published; TK, contribution to conception and design of the study, conduction of all experiments, statistical analysis of the data, revising the article critically for important intellectual content and final approval of the version to be published; DP, contribution to conception and design of the study, analysis of the histopathological damage of mice livers, interpretation of the data, drafting the article and final approval of the version to be published; FĆ, substantial contributions to conception and design of the study, interpretation of the data, revising the article critically for important intellectual content and final approval of the version to be published.…”