Current evidence indicates that
liver fibrosis is dynamic and can be bidirectional, involving phases of progression and regression, and that in addition to increased matrix synthesis, this pathological process involves major changes in the regulation of matrix degradation. There is also evidence that Kupffer cells participate in both fibrogenesis and fibrolysis. Therefore, the aim of the present work was to study the participation of Kupffer cells on the spontaneous resolution of hepatic
fibrosis.
Cirrhosis was produced by 3 months of chronic CCl(4) intoxication in male Wistar rats, and then CCl(4) was discontinued and two groups were formed: One group received
gadolinium chloride (10 mg/kg, IP, daily) and the other received the vehicle (water) only for 2 months. Serum
enzyme activities of
alkaline phosphatase and
alanine aminotransferase and liver lipid peroxidation increased by CCl(4) treatment but returned to normal by discontinuation of CCl(4). GSH, GSH/
GSSG, and GSH+GSSG decreased significantly by CCl(4), but withdrawal of CCl(4) restored normal
glutathione parameters.
Fibrosis increased five-fold and
glycogen decreased significantly by CCl(4) treatment, while discontinuation of CCl(4) reversed completely
glycogen depletion and partially
fibrosis.
Gadolinium chloride showed effects only in the content of
glycogen and
collagen; the former was decreased further and the latter remained elevated despite discontinuation of the toxic agent. Persistent
fibrosis induced by
gadolinium chloride, a selective inhibitor of Kupffer cells, indicates that these cells play a pivotal role in fibrolysis.