Pentoxifylline does not prevent neither liver damage nor early profibrogenic events in a rat model of non-alcoholic steatohepatitis.
BACKGROUND
Non-alcoholic steatohepatitis (NASH) is a metabolic disorder of the liver, which may evolve to fibrosis or cirrhosis. Pentoxifylline (PTX) has been postulated to act as an antifibrogenic agent able to inhibit hepatic stellate cell proliferation and collagen synthesis in vitro. Short-term studies suggest beneficial effects of PTX in experimental models of NASH.


OBJECTIVE
To study whether PTX can influence liver fibrogenesis in an animal model of NASH.


METHODS
To induce NASH, a choline-deficient diet (CDD) was given to Sprague- Dawley rats for 8 weeks. Rats were allocated to two experimental groups one receiving PTX (9 mg/kg/day) in drinking water. Control rats received a choline-supplemented diet. Biochemical and histological evaluation of fatty liver was performed by conventional techniques. In addition, mRNA levels of Pro-collagen I and transforming growth factor beta-1 were assessed by semi-quantitative RT-PCR and stellate cell activation by alpha-actin immunofluorescence stain.


RESULTS
After 8 weeks CDD induced a marked elevation of serum aminotransferases, a marked decrease in both hepatic and biliary glutathione and a severe fatty liver infiltration with mild histological inflammation and fibrosis. A significant increase in mRNA levels of both Pro-collagen I and TGFbeta-1 was seen after CDD feeding. No differences were seen between rats receiving PTX and rats on CDD diet alone with regard to the biochemical, morphological or molecular alterations induced by the CDD.


CONCLUSIONS
PTX does influence neither liver injury nor early profibrogenic events in the CDD model of NASH.
Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Paula
P
Vial
Arnoldo
A
Riquelme
Margarita
M
Pizarro
Nancy
N
Solís
Juan Andrés
JA
Madariaga
Gloria
G
Aguayo
Ignacio
I
Duarte
Alejandro
A
Soza
Luigi
L
Accatino
Marco
M
Arrese
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D009929:Organ Size; D010431:Pentoxifylline / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011347:Procollagen / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism; D017211:Treatment Failure
D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D011347:Procollagen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D010431:Pentoxifylline