Eicosanoid-dependent mechanisms in liver disease

Understanding the mechanisms of liver injury is based on defining the role and interplay of the individual cell types, which constitute the functioning liver, as both participants and targets of disease. The initiation and progression of liver injury involve the participation of intracellular and extracellular mediators: cytokines, chemokines, reactive oxygen species, nitric oxide, carbon monoxide, and eicosanoids. In particular, we will address the products of arachidonate metabolism, eicosanoids, a family of biologically active compounds that regulate metabolic as well as endocrine and hemodynamic functions of the liver. The several pathways of metabolism of arachidonic acid synthesize a multitude of compounds having diverse and opposing autocrine and paracrine activities. The role of eicosanoids in circulatory control, particularly of the hepatic and splanchnic circulations, is being clarified. However, very little information is available on the metabolic, pro-inflammatory and anti-inflammatory, as well as fibrotic and anti-fibrotic roles of eicosanoids in the liver. In this Special Issue, the role of arachidonate metabolites formed by oxygenases, namely, prostaglandins, leukotrienes and cytochrome P450-dependent metabolites, and reactive oxygen species, namely isoprostanes, will be reviewed in terms of their participation in the development of abnormalities associated with liver diseases. Our intention is to present an overview of what we know and what we would like to know about eicosanoids and the liver, and, thus, to stimulate research in this promising area. List of papers: (1) Eicosanoids in cirrhosis and portal hypertension. Yvonne Bimey, Eileen M. Redmond, James Sitzmann, Paol A. Cahill (2) Prostaglandins and other cyclooxygenase-dependent arachidonic acid metabolites and the kidney in liver disease. Joan Clària and Vicente Arroyo (3) Cysteinyl-leukotrienes and the liver. Ramin Farzaneh-Far and Kevin Moore (4) Role of cytochrome P450-dependent arachidonic acid metabolites in liver physiology and pathophysiology. David Sacerdoti, Angelo Gatta, John C. McGiff 1098-8823/$ – see front matter © 2003 Elsevier Inc. All rights reserved. doi:10.1016/S1098-8823(03)00079-0 2 Preface / Prostaglandins & other Lipid Mediators 72 (2003) 1–2 (5) F2-isoprostanes and the liver. Indra Neil Guha and Kevin Moore