Platelet-Activating Factor Involvement in Thioacetamide-Induced Experimental Liver Fibrosis and Cirrhosis

Abstract

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.

Thioacetamide Intoxication Triggers Transcriptional Up-Regulation but Enzyme Inactivation of UDP-Glucuronosyltransferases

“…In accordance with previous reports (Karantonis et al, 2010;Shaker et al, 2010), the study presented here confirmed that TAA treatment resulted in a significant retardation of natural body growth, liver hypertrophy, elevated serum biomarkers of liver function, and the progressive liver fibrosis. As expected, SLE and DDB treatments exhibited powerful hepatoprotective effects, supported by the significant recovery of most indexes determined.…”

Activation of platelet-activating factor receptor exacerbates renal inflammation and promotes fibrosis

“…There is evidence of PAF involvement in fibrosis in different organs, like liver and lung. 39,40 In our study, the attenuated renal dysfunction observed in PAFR KO mice correlated with lower levels of fibrosis. This is in accordance with results from Doi et al, 41 using the acid folic model of renal injury.…”

Platelet-activating factor modulates fat storage in the liver induced by a high-refined carbohydrate-containing diet

“…This increase would be related with a higher deposition of collagen in the liver because PAF signaling appears to be important to trigger fibrogenesis [47,51,52]. Moreover, the use of a PAF antagonist decreases fibrosis in other tissues such as lung and subretinal tissues [53,54].…”