Platelet activating factor (PAF) antagonism with ginkgolide B protects the liver against acute injury. importance of controlling the receptor of PAF.
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.
Grypioti
Agni D
AD
Department of Experimental Pharmacology, Medical School, National and Kapodistrian University of Athens, 25, Idaspou Street, Ano Ilisia, Athens 157 72, Greece. agrypiot@med.uoa.gr
Kostopanagiotou
Georgia
G
Demopoulos
Constantinos A
CA
Roussos
Anastasios
A
Mykoniatis
Michael
M
D000082:Acetaminophen / Q000506:poisoning*; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D046934:Ginkgolides / Q000627:therapeutic use*; D007783:Lactones / Q000627:therapeutic use*; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors
D018712:Analgesics, Non-Narcotic; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D007783:Lactones; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D000082:Acetaminophen; C045856:ginkgolide B