Platelet-activating factor involvement in thioacetamide-induced experimental liver fibrosis and cirrhosis.
Platelet-activating factor (PAF) is a potent lipid inflammatory mediator acting on cells through its specific receptor. Plasma PAF-acetylhydrolase (PAF-AH) is the main enzyme that inactivates PAF in blood, participating in its homeostasis. The objective of this study was to investigate the involvement of PAF in the liver fibrotic process using an experimental animal model. Liver fibrosis was induced in adult male Wistar rats by administration of thioacetamide (TAA) in drinking water (300 mg/l) for three months. The animals were sacrificed at time 0 (control group) and after 1, 2, and 3 months. PAF levels in liver and blood and PAF-AH activity in plasma were determined. Liver histopathological examination was also performed. TAA administration resulted in progressively increased liver fibrosis, leading finally to the formation of cirrhotic nodules in the liver. Throughout the experiment PAF levels in liver tissue remained stable. "Total" ("free" plus "bound") PAF levels in blood decreased, reaching statistically significant differences in the first and third months compared with the control group (P < 0.05). "Free" PAF levels in blood were higher at one month (P < 0.05) and decreased gradually thereafter. In all treated groups, "bound" PAF levels in blood decreased whereas plasma PAF-AH activity increased (P < 0.05) compared with the control group. Our data indicated alterations of PAF levels in blood and PAF-AH activity during fibrosis induction, implicating participation of PAF in the liver fibrotic process.
Karantonis
Haralabos C
HC
Department of Forensic Medicine and Toxicology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias str, 11527 Goudi, Athens, Greece.
Gribilas
Georgios
G
Stamoulis
Ioannis
I
Giaginis
Constantinos
C
Spiliopoulou
Chara
C
Kouraklis
Gregorios
G
Demopoulos
Constantinos
C
Theocharis
Stamatios E
SE
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013853:Thioacetamide / Q000633:toxicity
D010972:Platelet Activating Factor; D013853:Thioacetamide; D008315:Malondialdehyde