Pirfenidone effectively reverses experimental liver fibrosis.
OBJECTIVE
Our group has been involved in searching for different strategies to ameliorate hepatic cirrhosis. The aim of this study was to evaluate the effect of Pirfenidone in the reversion or prevention of cirrhosis experimentally induced in rats by chronic administration of CCl(4) and bile-duct ligation (BDL).


METHODS
Male cirrhotic Wistar rats (8 weeks of intoxication and then hepatotoxin was discontinued) received either oral saline or Pirfenidone at 500 mg/kg per day.


RESULTS
High levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase decreased significantly (P<0.001) in animals treated with Pirfenidone (n=11) with regard to saline-administrated animals (n=9). Prothrombin activity and bilirubins were also reduced. Computerized fibrosis index demonstrated a 70% decrease (P<0.001) along with less hydroxyproline content, reduction in activated HSC and higher active cell regeneration. A rearrangement of the parenchyma was also noted and gene expression of collagens I, III and IV, transforming growth factor beta-1, Smad-7, TIMP-1 and PAI-1 decreased considerably in treated animals. Cirrhotic rats in which CCl(4) was not discontinued displayed 40% liver fibrosis reduction. In a different cirrhosis model, 4-week BDL rats treated with the drug showed a significant 50% reduction in hepatic fibrosis (P<0.01).


CONCLUSIONS
This new drug might be useful in healing human disease.
García
Leonel
L
Institute for Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Apdo. Postal 2-123, Guadalajara, Jal. 44281, Mexico.
Hernández
Ivan
I
Sandoval
Ana
A
Salazar
Adriana
A
Garcia
Jesus
J
Vera
Jose
J
Grijalva
G
G
Muriel
Pablo
P
Margolin
Solomon
S
Armendariz-Borunda
Juan
J
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001652:Bile Ducts; D001663:Bilirubin / Q000097:blood; D002251:Carbon Tetrachloride; D006909:Hydroxyproline / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D008115:Liver Regeneration; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D011516:Prothrombin / Q000032:analysis; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D011728:Pyridones; D011516:Prothrombin; D002251:Carbon Tetrachloride; C093844:pirfenidone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D020778:Matrix Metalloproteinase 2; D001663:Bilirubin; D006909:Hydroxyproline