The beneficial effect of aspirin and enoxaparin on fibrosis progression and regenerative activity in a rat model of cirrhosis.
The aim of this study was to examine the effect of the antithrombotic drugs aspirin and enoxaparin on fibrosis progression and regenerative activity in a rat model of liver cirrhosis and to determine if these two drugs are beneficial in animals with advanced fibrosis or with established cirrhosis undergoing partial hepatectomy. Thioacetamide-induced cirrhotic rats received saline (N=10), aspirin (N=7), or enoxaparin (N=11) for a 5-week treatment period. Hepatic fibrosis was assessed according to METAVIR score. Liver regeneration was monitored using PCNA immunostaining. Compared to untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the aspirin (43%; chi(2)=54, P<0.001) and enoxaparin (36%; chi(2)=43, P<0.001) treated groups. Postoperatively, total serum bilirubin levels were lower in the aspirin (1.4+/-0.18 mg/dl; P<0.01) and enoxaparin (1.8+/-0.35 mg/dl; P<0.05)-treated groups compared to untreated cirrhotic controls (3.2+/-0.6 mg/dl). Hepatic regenerative activity was significantly improved in the aspirin group (57.3%+/-6.8%, versus 34.2%+/-7.2% in untreated cirrhotic controls; P<0.01) but unchanged in the enoxaparin group. We conclude that aspirin and enoxaparin hold promise as a useful therapy for patients with extensive fibrosis.
Assy
Nimer
N
Liver Clinic, Sieff Government Hospital, P.O.B. 1008, Safed 13100, Israel. assy.n@ziv.health.gov.il
Hussein
Osamah
O
Khalil
Abdallah
A
Luder
Anthony
A
Szvalb
Sergio
S
Paizi
Melia
M
Spira
Gadi
G
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D018450:Disease Progression; D017984:Enoxaparin / Q000494:pharmacology* / Q000627:therapeutic use; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005355:Fibrosis; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008115:Liver Regeneration / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013853:Thioacetamide
D017984:Enoxaparin; D005343:Fibrinolytic Agents; D018809:Proliferating Cell Nuclear Antigen; D013853:Thioacetamide; D001219:Aspartate Aminotransferases; D001241:Aspirin; D001663:Bilirubin