TAA and BDL caused significant liver dysfunction in rats and led
to obvious liver fibrosis
Elevated serum levels of ALT and AST are indicators of liver injury(17).
ALP levels are related to chronic liver injury(18). The serum levels of
ALT, AST and ALP and the liver weights of normal female rats were
significantly lower than those of male rats. The levels of ALT, AST, and
ALP and the liver weights or liver indexes were significantly increased
by BDL for 1 month and were much higher than those in rats treated with
TAA for 23 weeks. These data suggest that BDL for 1 month induced an
obvious inflammatory reaction in the livers of rats that was more potent
than that of TAA (Figure 1).
Fibrosis is the excessive accumulation of
collagen
and other extracellular matrix components (EMCs) such as fibronectin
(FN) and laminin (LN), due to chronic injury (19-21). Hydroxyproline is
a characteristic component of collagen, and the content of
hydroxyproline is related to the level of tissue fibrosis(22). As shown
in Table 1, hydroxyproline in the livers of female rats was
significantly higher than that in those of male rats. In addition, 1
month after BDL, the increase in hydroxyproline was significantly higher
in female rats than in male rats treated with TAA for 23 weeks but BDL
for 1 month showed lower pathological scoring, suggesting that the
hydroxyproline level in liver was not completely proportional to the
degree of fibrosis. The mediastinal form and connective tissue
hyperplasia in the liver were more obvious in TAA rats than in BDL rats
(Table 1, Figure 2), and α-SMA, the marker of HSC activation, was
upregulated in the livers of BDL and TAA rats (Figure 3).
The
effect of BDL on the levels of ILs in female rats is different from the
effect of TAA in male rats
ILs include many cytokines that play an important role in liver injury
or fibrosis. Many cells can synthesize or secrete ILs. Many cells can
synthesis or secretion of ILs. As Figure 4 shows, the levels of
interleukins, especially IL-4, IL-10, IL-13, IL-18 and L-12p70, in liver
tissue of female rats were higher than those in the liver tissue of male
rats. After BDL or TAA treatment, IL-1α, IL- 4 and IL-10 decreased, but
IL-18 increased; BDL for a month upregulated IL-1β in the livers of
female rats but had no significant effect on IL-6 and IL-12p70, while
TAA decreased IL-1 β, IL-6 and IL-12p70 levels in the livers of male
rats (Figure 4).