PMID- 11584363
OWN - NLM
STAT- MEDLINE
DCOM- 20011018
LR  - 20131121
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 34
IP  - 4 Pt 1
DP  - 2001 Oct
TI  - Adenosine reverses a preestablished CCl4-induced micronodular cirrhosis through 
      enhancing collagenolytic activity and stimulating hepatocyte cell proliferation 
      in rats.
PG  - 677-87
AB  - Cirrhosis is one of the most common causes of mortality worldwide, because 
      hepatic dysfunction constitutes a potentially lethal condition. Having 
      demonstrated the hepatoprotective effect of adenosine against CCl(4)-induced 
      cirrhosis, the present study was aimed at assessing adenosine's effect on an 
      already-established micronodular cirrhosis. Chronic administration of CCl(4) (10 
      weeks) induced a cirrhotic state, characterized by increased liver fibronectin 
      and collagen types I and III content, enhanced expression of alpha-1 (I) collagen 
      mRNA, portal hypertension, and liver dysfunction. After CCl(4) discontinuation (5 
      weeks), increased persitance of alpha-1 (I) collagen mRNA expression and 
      deposition, enhanced proline incorporation into collagen and prolyl hydroxylase 
      activity evidenced active fibrogenesis. Several weeks after CCl(4) withdrawal, 
      deposited collagen showed an enhanced type I/III ratio, which was associated with 
      deficient collagenolytic activity in cirrhotic livers. Liver expression of some 
      metalloproteinases (MMPs) and of tissue inhibitors of MMPs (TIMPs) also indicated 
      decreased collagen breakdown in cirrhotic livers. Parameters indicative of 
      oxidative stress (mainly protein oxidation) were persistently augmented. These 
      events were coincident with diminished regenerative capacity of the cirrhotic 
      liver. Intraperitoneal adenosine administration to CCl(4)-induced cirrhotic rats 
      blocked active fibrogenesis and increased the collagen degradation (most probably 
      by decreasing liver TIMPs levels), normalizing collagen-type ratios. In addition, 
      the nucleoside promoted an effective hepatocyte's proliferation in the cirrhotic 
      liver and accelerated normalization of parameters indicative of liver function 
      and oxidative stress. Thus, adenosine readily reversed an experimental cirrhosis 
      through stimulating liver collagenolytic and proliferative capacities, as well as 
      by accelerating functional recovery.
FAU - Hernandez-Munoz, R
AU  - Hernandez-Munoz R
AD  - Departamento de Biologia Celular, Instituto de Fisiologia Celular, Universidad 
      Nacional Autonoma de Mexico.
FAU - Diaz-Munoz, M
AU  - Diaz-Munoz M
FAU - Suarez-Cuenca, J A
AU  - Suarez-Cuenca JA
FAU - Trejo-Solis, C
AU  - Trejo-Solis C
FAU - Lopez, V
AU  - Lopez V
FAU - Sanchez-Sevilla, L
AU  - Sanchez-Sevilla L
FAU - Yanez, L
AU  - Yanez L
FAU - De Sanchez, V C
AU  - De Sanchez VC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Fibronectins)
RN  - 9007-34-5 (Collagen)
RN  - 9007-49-2 (DNA)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*therapeutic use
MH  - Animals
MH  - Carbon Tetrachloride/*toxicity
MH  - Cell Division/drug effects
MH  - Collagen/analysis/*metabolism
MH  - DNA/biosynthesis
MH  - Fibronectins/analysis
MH  - Hepatocytes/*drug effects/metabolism
MH  - Hypertension, Portal/prevention & control
MH  - Liver/chemistry/metabolism
MH  - Liver Cirrhosis, Experimental/*drug therapy/metabolism
MH  - Liver Regeneration/drug effects
MH  - Male
MH  - Oxidative Stress
MH  - Rats
MH  - Rats, Wistar
EDAT- 2001/10/05 10:00
MHDA- 2001/10/19 10:01
CRDT- 2001/10/05 10:00
PHST- 2001/10/05 10:00 [pubmed]
PHST- 2001/10/19 10:01 [medline]
PHST- 2001/10/05 10:00 [entrez]
AID - S0270-9139(01)50376-6 [pii]
AID - 10.1053/jhep.2001.27949 [doi]
PST - ppublish
SO  - Hepatology. 2001 Oct;34(4 Pt 1):677-87. doi: 10.1053/jhep.2001.27949.