Liver cytoprotection by prostaglandins

Abstract

During the last decade intensive work on the relationships between the liver and the arachidonic acid cascade has greatly expanded our knowledge of this area of research. The liver has emerged as the major organ participating in the degradation and elimination of arachidonate products of systemic origin. The synthesis in the liver of arachidonate products derived from the cyclooxygenase, lipoxygenase and cytochrome P450 system pathways has been demonstrated. The participation of leukotriene B4 and cysteinyl-leukotrienes as mediators of liver damage and the possible therapeutic usefulness of prostaglandins (PGs) in acute liver injury has attracted the interest of clinicians. This article reviews the essential features regarding the role of arachidonate metabolites in liver disease and specially focuses on the cytoprotective effects on the liver displayed by PGE2, PGE1, PGI2 and synthetic PG analogs in experimental models of liver damage induced by ischemia-reperfusion injury, carbon tetrachloride, bacterial lipopolysaccharide and viral hepatitis and on the possible mechanisms underlying liver cytoprotection in these experimental models. The therapeutic usefulness of PGs in clinical practice is critically analyzed on the basis of available evidence in patients with fulminant hepatic failure and primary graft nonfunction following liver transplantation.

Prevention of reperfusion injury and microcirculatory failure in macrosteatotic mouse liver by omega-3 fatty acids

“…Owing to their role in production of injurious eicosanoids that aggravate the outcome after hepatic I/R, 21 we assessed the influence of n-3 PUFA supplementation on Kupffer cell activation. Determination of kinetics of fluorescence-labeled latex particles revealed dampened activity of Kupffer cells in the n-3 PUFAs group compared with control diet.…”

Treatment of fulminant hepatic failure with intravenous prostaglandin E1

“…Prostaglandins are biologically active, polyunsaturated fatty acids arising from arachidonic acid. 22 Although they are produced in all cells, the liver is particularly rich in prostaglandins of the E series. The cytoprotective effect of prostaglandins in gastric mucosa has been known for decades.…”

“…[20][21][22][23][24] Preliminary trials in humans also suggest that prostaglandins are useful in the treatment of FHF. [25][26][27] In an open-label pilot study conducted by Sinclair et al, 70% of patients with FHF treated with prostaglandins survived without the need for hepatic transplantation.…”

Importancia de las prostaglandinas en la amibiasis hepática

“…49 Aunque la liberación de estos agentes juega un papel básicamente protector para la homeostasis del tejido, 50 puede contribuir al establecimiento de ciertos agentes infecciosos.…”

“…Posterior a la depleción de la capa de moco los trofozoitos se adhieren a las células epiteliales y, previa lisis de las mismas, proceden a invadir el tejido. 50 La producción de citocinas proinflamatorias del tipo de la IL-8 ha sido estudiada in vitro, utilizando la línea celular T84 de adenocarcinoma de colon. En este modelo se demostró que la interacción del parásito con componentes de secreción, proteínas solubles y el contacto célula-célula, induce la producción de altos niveles del mRNA de la IL-8.…”