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

  • Ivan Ćavar | ivancavarsb@yahoo.com Department of Physiology, Faculty of Medicine, University of Mostar, Bosnia and Herzegovina.
  • Tomislav Kelava Department of Physiology, Faculty of Medicine, University of Zagreb, Croatia.
  • Danijel Pravdić Department of Physiology, Faculty of Medicine, University of Mostar, Bosnia and Herzegovina.
  • Filip Čulo Department of Physiology, Faculty of Medicine, University of Mostar, Bosnia and Herzegovina; Department of Physiology, Faculty of Medicine, University of Zagreb, Croatia, Bosnia and Herzegovina.

Abstract

Prostanoids are lipid compounds that mediate a variety of physiological and pathological functions in almost all body tissues and organs. Thromboxane (TX) A2 is a powerful inducer of platelet aggregation and vasoconstriction and it has ulcerogenic activity in the gastrointestinal tract. Overdose or chronic use of a high dose of acetaminophen (N-acetyl-paminophenol, APAP) is a major cause of acute liver failure in the Western world. We investigated whether TXA2 plays a role in host response to toxic effect of APAP. CBA/H Zg mice of both sexes were intoxicated with a single lethal or high sublethal dose of APAP, which was administered to animals by oral gavage. The toxicity of APAP was determined by observing the survival of mice during 48 h, by measuring concentration of alanine-aminotransferase (ALT) in plasma 20-22 h after APAP administration and by liver histology. The results have shown that anti-thromboxane (TX) B2 antibodies (anti-TXB2) and a selective inhibitor of thromboxane (TX) synthase, benzylimidazole (BZI), were significantly hepatoprotective, while a selective thromboxane receptor (TPR) antagonist, daltroban, was slightly protective in this model of acute liver injury. A stabile metabolite of TXA2, TXB2, and a stabile agonist of TPR, U-46619, had no influence on APAP-induced liver damage. Our findings suggest that TXA2 has a pathogenic role in acute liver toxicity induced with APAP, which was highly abrogated by administration of anti-TXB2. According to our results, this protection is mediated, at least in part, through decreased production of TXB2 by liver fragments ex vivo.

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Published
2011-12-21
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Original Articles
Supporting Agencies
Ministry of Sciences, Higher Education and Sports of Republic of Croatia, Ministry of Sciences and Education of Federation of Bosnia and Herzegovina
Keywords:
thromboxane A2, anti-TXB2 antibodies, acetaminophen, liver.
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How to Cite
Ćavar, I., Kelava, T., Pravdić, D., & Čulo, F. (2011). Anti-thromboxane B2 antibodies protect against acetaminophen-induced liver injury in mice. Journal of Xenobiotics, 1(1), e8. https://doi.org/10.4081/xeno.2011.e8