Metronidazole induces prostaglandin E2 formation via arachidonic acid production in protozoan parasite Giardia lamblia

Abstract

The causative agent of giardiasis in human and animals is the amitochondriate Giardia lamblia. We observed that exposing Giardia trophozoites to MTZ led to an increase in lipid peroxidation compared to the control group, which was expressed in terms of menadione production as it is the marker for lipo-peroxidation. Oxidative stress generated by reactive nitrogen species and peroxidation of membrane phospholipids are positively correlated with the enhanced PLA2 activity in several organisms to produce arachidonic acid (AA). Our data suggested Giardia produces a unique 56 kDa dimeric enzyme called Phospholipase B (gPLB) in contrast to higher eukaryotes which was responsible for the production of intracellular free AA. This free AA either reacylates to the cell membrane or deacylates to further produce prostaglandins. In normal un-induced controlled trophozoites the membrane reacylation process was dominant due the higher level of acyle CoA synthase (ACS) expression over the time. However, under the oxidative stressed condition the intracellular ACS expression was down regulated. This led to the increase in deacylation process. When AA deacylation becomes dominant over AA reacylation in cells, the free AA accumulates intracellularly. One of the lipid autacoids, derived from AA is prostaglandin2 (PGE2). Oxidative stress generated by reactive nitrogen species in trophozoites increased the PGE2 production via prostaglandin synthase over the time with respect to the controlled one.