Iron deposition and fat accumulation in dimethylnitrosamine-induced liver fibrosis in rat

Abstract

Aim: To investigate if iron deposition and fat accumulation in the liver play a pathogenetic role in dimethylnitrosamine (DMN)-induced liver fibrosis in rat.

Methods: Thirty rats were treated with DMN at does consecutive days of 10 microL/kg daily, i.p., for 3 consecutive day each week for 4 wk. Rats (n=30) were sacrificed on the first day (model group A) and 21(st) d (model group B) after cessation of DMN injection. The control group (n=10) received an equivalent amount of saline. Liver tissues were stained with hematoxylin and eosin (HE) and Masson and Prussian blue assay and observed under electron microscopy. Serum alanine aminotransferase (ALT) and liver tissue hydroxyproline (Hyp) content were tested.

Results: The liver fibrosis did not automatically reverse, which was similar to previous reports, the perilobular deposition of iron accompanied with collagen showed marked characteristics at both the first and 21(st) d after cessation of DMN injection. However, fat accumulation in hepatocytes occurred only at the 21(st) d after cessation of DMN injection.

Conclusion: Iron deposition and fat accumulation may play important roles in pathological changes in DMN-induced rat liver fibrosis. The detailed mechanisms of these characteristics need further research.

Figure 1

Schematic representation of the DMN treatment protocol.

Figure 2

Liver histopathology of DMN-treated rats (HE). A: Control group, no marked pathological changes (× 400); B: Group model A, hemorrhagic necrosis with foci of lymphomonocytic infiltration around fibrosis tissue can be seen (× 400); C: Group model B, fat accumulated in numerous liver cells (× 400); D: Group model B, quantities of fiber deposited and linked with each other (× 400).

Figure 3

Rat liver fibrosis induced by DMN (Masson). A: Group model A, the green fiber distributed between liver cells and accompanied with necrotic hemorrhage; B: Group model B, similar to group model A in fibrosis (× 400).

Figure 4

Ultrastructural changes of the liver in DMN-treated rats. A: model group A, no marked lipid drops deposited in the liver cells and from which we also can see an erythrocyte pass through extracellular matrix and closely stick to the liver cell membrane; B: model group B, numerous lipid drops deposited in liver cell (electron microscopy, × 6000).

Figure 5

Iron deposition in rat liver induced by DMN (Prussian blue). A: model group A, the iron is mainly accompanied by fiber (× 100); B: model group B, similar to the model A in iron deposition, iron nodules are deep blue in color and mainly located extracellularly or in the Kupffer cells (× 400).