6533b7d3fe1ef96bd126155e

RESEARCH PRODUCT

Avarol restores the altered prostaglandin and leukotriene metabolism in monocytes infected with human immunodeficiency virus type 1

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Abstract Infection of monocytes with human immunodeficiency virus type 1 (HIV-1) (strain Ada-M) caused increased levels of leukotriene B 4 (LTB 4 ) and prostaglandin E 2 (PGE 2 ) in vitro. These two products result from the activities of the two enzymes cyclooxygenase and 5-lipoxygenase. The addition of the sesquiterpenoid hydroquinone Avarol, an HIV inhibitor, strongly reduced the levels of LTB 4 and PGE 2 via inhibition of both cyclooxygenase and lipoxygenase in monocytes. The 50% inhibition concentrations (IC 50 ) for the enzymes were determined to be 2.26 μM (cyclooxygenase) and 1.97 μM (lipoxygenase). A 50% reduction of the extent of PGE 2 and LTB 4 production in HIV-infected monocytes was measured at a concentration of 0.9 μm Avarol, a dose which caused an 80% anti-HIV effect in vitro (50% inhibition of virus release from infected cells: 0.3 μm). We conclude that Avarol inhibits the enzymes cyclooxygenase and lipoxygenase and suggest that, in general, inhibitors of these enzymes are promising anti-HIV compounds.