F₂-isoprostane induced prostaglandin formation in the rabbit

Abstract

F(2)-isoprostanes, non-enzymatic free radical mediated products of arachidonic acid, have shown to form during various oxidant stress status and have potent biological effects. This study investigates to what extent 8-iso-PGF(2alpha) (a major F(2)-isoprostane), a bioactive product of lipid peroxidation can modify endogenous prostaglandin F(2alpha) (PGF(2alpha)) formation since prostaglandins are inflammatory as well as potent vasoregulatory substances that modulate diverse important physiological functions, and also form during acute and chronic inflammation. An immediate appearance and disappearance of 8-iso-PGF(2alpha) was seen in both plasma and urine within a short interval after i.v. administration of 43 microg/kg of 8-iso-PGF(2alpha) to the rabbits. A successive but differential formation of PGF(2alpha) resulted in a rapid and pulsatile increase of plasma 15-keto-dihydro-PGF(2alpha), a major metabolite of primary PGF(2alpha). Later, this compound was excreted efficiently as intact compound into the urine during the 3 h of experiment. A 8-fold increase of PGF(2alpha) metabolite in plasma at 10 min and 12-fold increase in the urine at 30-60 after the i.v. administration of 8-iso-PGF(2alpha) was observed which continued throughout the 3 h of experiment. This observation suggests that pharmacologically administered or endogenously produced 8-iso-PGF(2alpha) during oxidant stress induces prostaglandin formation presumably through the classical cyclooxygenase-catalysed arachidonic acid oxidation which might be inflammatory itself to the cells and exerts further vasoconstrictive effects.

Prejunctional Inhibitory Effects of Isoprostanes on Dopaminergic Neurotransmission in Bovine Retinae, In vitro

“…Similarly, pretreatment of isolated bovine retinal tissues with flurbiprofen abolished the stimulatory effect of 8-isoPGF 2a on K + -induced [ 3 H]D-aspartate release [9]. In the systemic circulation, there is evidence that intravenous injection of 8-isoPGF 2a can induce an immediate appearance and disappearance of PGF 2a in rabbit plasma and urine, suggesting these IsoPs do indeed lead to production of PGs in some tissues [27]. Taken together, these data suggest that endogenously derived arachidonic acid metabolites contribute to the inhibitory effect of IsoPs on K + -induced [ 3 H]dopamine release.…”

ReviewIsoprostanes: Novel Bioactive Products of Lipid Peroxidation

“…Recently, it was shown in rabbits that intravenous administration of 8-iso-PGF 2a induced COX-mediated PGF 2a formation which have shown to be related to inflammation. [59,17,50,120] Formation of COX-mediated PGF 2a has also been seen subsequent to CCl 4 -induced F 2 -isoprostane production in rats, showing that these two structurally closely related but biosynthetically distinct compounds have diviant kinetics of biosynthesis and release, and indirectly supports the view of activation of cyclooxygenases and inflammatory responses. [33,34] However, further research on the mechanism of PGF 2a formation induction by 8-iso-PGF 2a is needed to clarify this phenomenon further.…”

“…[122] Thus, isoprostanes seem to be involved in acute inflammatory condition. Recently, an upregulation of inflammatory gene expression through activation of MAPKs pathway as shown by the induction of cytokine (IL-6) in human macrophages, [123] and prostaglandin F 2a formation [33,59] through COX pathway by F 2 -isoprostanes are reported. The excretion of F 2 -isoprostanes was related to the rate of atherogenesis and the high level of oxidised LDL in mice, but was not influenced by extra cellular-superoxide dismutase (EC-SOD) genotype mice.…”

“…[123] Together, these studies emphasize that F 2 -isoprostane might be a mediator of inflammation, involving cyclo-oxygen and/or cytokines and a possible link between oxidative stress and inflammation. [33,59] Those isoprostanes or related compounds that are derived from eicosapentaenoic acid or docosahexaenoic acid seem to have only marginal or no biological effects. [13,60] …”

The enigma of in vivo oxidative stress assessment: isoprostanes as an emerging target

“…Several of these compounds retain biological activities, as confirmed mainly by pulmonary and vasoconstrictive, and even inflammatory activities (2,3). Both human and experimental studies reveal that isoprostanes are augmented in both acute and severe chronic inflammation, ischaemiaÁreperfusion, diabetes, atherosclerosis, obesity, lung and liver diseases, etc (see Table 1).…”