Modification of pathobiological events by potential hepatopharmacological agents

A. Jeney, I. Kovalszky, F. Timar, Z. Schaff, A. Zalatnai, K. Lapis, J. Olah, A. Divald, B. Szende

Research output: Contribution to journalArticle

Abstract

The elucidation of the pathobiological events in chronic liver diseases - such as cellular injury, cell proliferation, remodelling of extracellular matrix - has considerable importance for establishing the rational bases of hepatopharmacology. To follow this concept, the molecular-pathological features of chemically induced liver damage in rats were characterized and modulated by potential hepatopharmacological compounds. Among the 55 chemical compounds tested, acute liver damage could be most effectively abolished by prostacyclin (PGI2). In addition, prostacyclins were also able to prevent cirrhosis in experimental animals. The modes of action of the prostacyclins were investigated in short-term hepatocyte culture. The hepatotoxin-induced metabolic alterations (reduced gluconeogenesis and protein synthesis, lipid peroxidation, etc.) could be restored by prostacyclin. It was shown that PGI2 could circumvent the augmented catabolic rate of 4,5-phosphatidyl inositol-diphosphate (PIP2) in CCl4-induced hepatocyte injury. In addition, the increased intracellular calcium concentration in the injured cells was also normalized by PGI2. Thus, PIP2 metabolism appears to be a critical process in the mechanism of hepatocyte damage and its protection. Interestingly, PGI2 was effective at an advanced stage of liver injury, whereas thiazolidines were only active when administered before the application of the hepatotoxic agent. The formation of collagen could be reduced by amino-imidazolcarboxamide and silymarin. The increase in glycosaminoglycans could be abolished by the application of 5-hexyl-2-deoxyuridine. The presented data provide further evidence that compounds with various targets are required in hepatopharmacology.

Original languageEnglish
Pages (from-to)93-103
Number of pages11
JournalInflammopharmacology
Volume5
Issue number1
Publication statusPublished - 1997

Fingerprint

Epoprostenol
Prostaglandins I
Hepatocytes
Liver
Wounds and Injuries
Thiazolidines
Silymarin
Gluconeogenesis
Diphosphates
Phosphatidylinositols
Glycosaminoglycans
Lipid Peroxidation
Extracellular Matrix
Liver Diseases
Fibrosis
Chronic Disease
Collagen
Cell Proliferation
Calcium
Proteins

Keywords

  • hepatopharmacological agents
  • prostacyclin

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

Modification of pathobiological events by potential hepatopharmacological agents. / Jeney, A.; Kovalszky, I.; Timar, F.; Schaff, Z.; Zalatnai, A.; Lapis, K.; Olah, J.; Divald, A.; Szende, B.

In: Inflammopharmacology, Vol. 5, No. 1, 1997, p. 93-103.

Research output: Contribution to journalArticle

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