Prostanoid production in endothelial and Kupffer liver cells from monocrotaline intoxicated rats

Abstract

A single dose of monocrotaline, a pyrrolizidine alkaloid, was injected into rats in order to produce 25 (Group I) and 45 (Group II) days later a progressive and so called delayed liver injury. The present study investigated the prostanoid production of Kupffer cells and endothelial cells separated from Monocrotaline and saline (Group III) injected rat livers. Kupffer cells: formation of 6 keto Prostaglandin F₁ _a, the major prostacyclin metabolite, gradually decreased in Groups I vs II (P50.01) and in both Groups I and II vs Controls (P50.01). In addition Prostaglandin F₂ _a showed a significant increase in Groups I and II when compared to Group III, (P50.001), and Thromboxane B2 was present in both Groups of Monocrotaline treated animals, while it was not detectable in the control Group III. Endothelial cells:6ketoProstaglandin F₁ _a decreased in Groups I vs II. This differences was significant when compared, and compared to controls (Group III, P50.001). Prostaglandin E₂ was detected only in Groups I and II. Prostaglandin F₂ _a and Thromboxane B₂ could not be detected in any Group. Ultramicroscopy showed morphological cell damage in nonparenchymal cells in Monocrotaline intoxication in Group II, rats sacrified 45 days after the injection, while it shows normal features in those treated animals sacrified 25 days after the injection, as well as in control group. Conclusion: Asingle Monocrotaline injection produces, 25 and 45 days later, severe and progressive alterations in the prostanoid production in Kupffer and Endothelial cells, while ultramicroscopic alterations was only observed 45 days after the injection of Monocrotaline. A decreased production of vasodilators and the presence of vasoconstrictor prostanoids that can participate in the production of the circulatory derangements enhancing liver injury and portal hypertension were also observed.

Keywords

prostanoids endothelial cells Kupffer cells monocrotaline liver injury

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