Platelet-activating factor inactivator (rPAF-AH) enhances liver's recovery after paracetamol intoxication.
Platelet-activating factor (PAF) is a potent endogenous phospholipid modulator of diverse biological activities, including inflammation. The aim of this study was to investigate the effects of PAF inactivator, recombinant PAF acetylhydrolase (rPAF-AH) on post-paracetamol treatment functional outcome of the liver in the rat. Fifty male Wistar rats were divided into two groups: the control group received by gastric tube a toxic dose of paracetamol (3.5 g/kg body weight) and the rPAF-AH-treated group received the same dose of paracetamol followed by a dose of rPAF-AH (10 mg/kg body weight) intraperitoneally. The animals were sacrificed at 8, 16, 24, 32, and 40 hr after paracetamol treatment. APAP was found to cause acute hepatic injury, evident by alterations of biochemical (serum enzymes: ALT, AST, and ALP) and liver histopathological (degree of inflammation and apoptosis) indexes, which was followed by liver regeneration evident by three independent indexes ([(3)H]thymidine incorporation into hepatic DNA, liver thymidine kinase activity, and hepatocyte mitotic index). Hepatic levels of malondialdehyde (MDA) and serum cholesterol/HDL cholesterol fraction were also measured as parameters of oxidant-antioxidant balance. The positive effects of rPAF-AH were expressed by (1) a reduction of oxidative stress, (2) a large decrease in hepatic injury, and (3) a reduction of regenerating activity. These results suggest that PAF plays an important role in paracetamol-induced liver injury and regeneration. Furthermore, PAF inactivator enhances liver's recovery and attenuates the severity of experimental liver injury, providing important means of improving liver function following paracetamol intoxication.
Grypioti
A D
AD
Department of Experimental Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. agrypiot@med.uoa.gr
Kostopanagiotou
G
G
Mykoniatis
M
M
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000009:adverse effects / Q000627:therapeutic use*; D000082:Acetaminophen / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003124:Colorimetry; D004247:DNA / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D020127:Recovery of Function / Q000187:drug effects*; D013937:Thymidine Kinase / Q000378:metabolism; D000637:Transaminases / Q000097:blood; D014461:Ultracentrifugation
D018712:Analgesics, Non-Narcotic; D011994:Recombinant Proteins; D000082:Acetaminophen; D008315:Malondialdehyde; D004247:DNA; D000637:Transaminases; D013937:Thymidine Kinase; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase