Recombinant platelet-activating factor-acetylhydrolase attenuates paracetamol-induced liver oxidative stress, injury, and regeneration.
The aim of this study was to investigate the effects of platelet-activating factor (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 a toxic dose of paracetamol (3.5 g/kg body weight [BW]) by gastric tube and the rPAF-AH-treated group received the same dose of paracetamol followed by a dose of rPAF-AH (10 mg/kg BW) intraperitoneally. The animals were sacrificed at time points of 56, 66, 72, 84, and 96 hr after paracetamol treatment. Hepatic injury was evaluated by determination of AST, ALT, and ALP activities and degree of necrosis and apoptosis. Liver regeneration was estimated by [3H]thymidine incorporation into hepatic DNA, liver thymidine kinase activity, and hepatocyte mitotic index. Hepatic levels of malondialdehyde (MDA) and serum cholesterol/high-density lipoprotein cholesterol fraction were also measured as parameters of oxidant-antioxidant balance. The positive effects of rPAF-AH were expressed by (1) reduction of oxidative stress, (2) large decrease in hepatic injury, and (3) diminution of regenerating activity. These results indicate that the use of PAF inactivator enhances the liver's recovery from paracetamol intoxication 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, 25 Idaspou Street, Ano Ilisia, GR 157 72, Athens, Greece. agrypiot@med.uoa.gr
Mykoniatis
M
M
Demopoulos
C A
CA
Kostopanagiotou
G
G
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000494:pharmacology*; D000082:Acetaminophen / Q000494:pharmacology / Q000506:poisoning; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology / Q000506:poisoning; D000818:Animals; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D011994:Recombinant Proteins; D000082:Acetaminophen; D008315:Malondialdehyde; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase