Τίτλος:
Platelet activating factor (PAF) antagonism with ginkgolide B protects the liver against acute injury. Importance of controlling the receptor of PAF
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Platelet activating factor (PAF) is an ubiquitous phospholipid that acts as a mediator of numerous pathophysiological conditions, including hepatotoxicity. The present study has been conducted to evaluate the eventual role of the platelet activating factor in post-acetaminophen intoxication of liver, using ginkgolide B, BN52021, a selective PAF receptor antagonist. One group of rats was treated with a toxic dose of acetaminophen (APAP) (3.5 g/kg b.w.) (control group) and a second one with the same dose of APAP followed by a dose of ginkgolide B, BN52021 (10 mg/kg b.w.) (BN52021-treated group). The animals were killed at 8, 16, 24, 32 and 40 h after treatment. APAP was found to cause an acute hepatic injury, evident by alterations of biochemical (serum enzymes: ALT, AST and ALP) and liver histopathological (degree of inflammation and apoptosis) indices, which was followed by liver regeneration evident by three independent indices ([3H] thymidine incorporation into hepatic DNA, liver thymidine kinase activity and hepatocyte mitotic index). Hepatic levels of malondialdehyde and serum cholesterol/HDL cholesterol fraction were also measured as parameters of oxidant-antioxidant balance. The protected effects of ginkgolide B were qualified during post treatment time by: (1) reduction of oxidative stress, (2) high decrease of hepatic injury, and (3) decrease of regenerating activity. These results indicate that PAF may play an important role in APAP-induced liver injury and regeneration, and that the use of ginkgolide B attenuates liver damage providing important means of improving liver function following acetaminophen intoxication. © 2007 Springer Science+Business Media, LLC.
Συγγραφείς:
Grypioti, A.D.
Kostopanagiotou, G.
Demopoulos, C.A.
Roussos, A.
Mykoniatis, M.
Περιοδικό:
Digestive Diseases and Sciences
Λέξεις-κλειδιά:
alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; ginkgolide B; high density lipoprotein; malonaldehyde; paracetamol; thrombocyte activating factor receptor; thymidine; thymidine kinase, animal experiment; animal model; animal tissue; apoptosis; article; controlled study; drug mechanism; enzyme activity; histopathology; liver cell; liver injury; liver protection; liver regeneration; male; mitosis; nonhuman; oxidative stress; priority journal; protein blood level; rat, Acetaminophen; Analgesics, Non-Narcotic; Animals; Disease Models, Animal; Fibrinolytic Agents; Ginkgolides; Lactones; Liver Diseases; Liver Regeneration; Male; Platelet Membrane Glycoproteins; Rats; Rats, Wistar; Receptors, G-Protein-Coupled
DOI:
10.1007/s10620-007-9982-2
