The effects of thromboxane A 2 inhibitors (OKY-046 and ONO-3708) and leukotriene inhibitors (AA-861 and LY-171883) on CCl 4-induced chronic liver injury in mice

Abstract

The effects of OKY-046, a selective thromboxane A 2 (TxA 2) synthetase inhibitor, ONO-3708, a novel TxA 2 receptor antagonist, AA-861, a selective 5-lipoxygenase inhibitor and LY-171883, a peptide leukotrienes (p-LTs) receptor antagonist on the chronic liver injury were investigated in mice. The chronic liver injury was induced by the injection of carbon tetrachloride (CCl 4) two times a week for twelve weeks in mice. In chronic liver injury models, significant histopathological changes in the liver and extensive elevation of glutamate transaminase (GOT and GPT) activity were observed. Administration of OKY-046, ONO-3708, AA-861 and LY-171883 for 12 weeks suppressed the elevation of serum GOT and GPT levels and histopathological changes in CCl 4-induced chronic liver injury. These results suggest that TxA 2 and LTs inhibitors are effective for the onset and development of chronic liver injury in mice.