Serotonin receptor 2 blockade can arrest liver regeneration only when administered close to G1/S transition point, and that while serotonin may be a cofactor for DNA synthesis, it does not play a role in initiation of liver regeneration.

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The observed variations of HSS activity in rat liver suggest active participation of this growth factor in hepatocyte replication which follows toxin-induced liver injury as a repair mechanism process.

BackgroundWe examined the intrinsic hepatic innervation after partial hepatectomy (PH) in rats and the presence and pattern of neural sprouting in regenerating liver.MethodsMale Wistar rats (age 9–13 weeks-w, weight 204-356 g), were submitted to two-thirds PH. Rats were sacrificed at postoperative days (d) 1, 3, 5, 7, at 2 and 4 w, and at 3 and 6 months (m) (6–7 animals/group, control group n = 4). Immunohistochemistry for the pan-neural marker protein gene product 9.5 (PGP9.5) and growth-associated protein 43 (GAP-43), a marker of regenerating nerve axons, was performed on tissue sections from the R1 lobe of the regenerating liver. Portal tracts (PTs) with immunoreactive fibers were counted in each section and computer-assisted morphometric analysis (Image Pro Plus) was used to measure nerve fiber density (number of immuno-positive nerve fibers/mm2 (40x)).ResultsImmunoreactivity for PGP9.5 was positive in all groups. The number of PGP9.5 (+) nerve fibers decreased from 0.32 +/− 0.12 (control group) to 0.18 +/− 0.09 (1d post-PH group), and gradually increased reaching pre-PH levels at 6 m (0.3 +/− 0.01). In contrast, immunoreactivity for GAP-43 was observed at 5d post-PH, and GAP-43 (+) PTs percentage increased thereafter with a peak at 3 m post-PH. GAP-43 (+) nerve fiber density increased gradually from 5d (0.05 +/− 0.06) with a peak at 3 m post-PH (0.21 +/− 0.027). At 6 m post-PH, immunoreactivity for GAP-43 was not detectable.ConclusionsFollowing PH in rats: 1) nerve fiber density in portal tracts decreases temporarily, and 2) neural sprouting in the regenerating liver lobes starts at 5d, reaches peak levels at 3 m and disappears at 6 m post-PH, indicating that the increase in hepatic mass after PH provides an adequate stimulus for the sprouting process.

The liver is of central importance in the metabolism of essential and toxic metals such as cadmium (Cd). Cd pretreatment suppressed the regenerative capacity of hepatocytes, which normally occurs 24 hr after partial hepatectomy, due to the inhibition of the activity of the enzyme thymidine kinase. The effect of hepatic stimulator substance (HSS) administration (10, 20, and 40 mg protein/kg body weight) on hepatocyte proliferation was investigated in Cd-pretreated partially hepatectomized rats. HSS administration partly restored the suppressed hepatocyte DNA biosynthesis in Cd-pretreated partially hepatectomized rats. The hepatocyte mitotic activity and the percentage of proliferating cell nuclear antigen-positive nuclei were in accordance with the liver proliferative status. The administration of HSS did not affect in a statistically significant manner the activity of the enzyme thymidine kinase in Cd-pretreated partially hepatectomized rats. It is suggested that the administration of HSS ameliorates the diminished hepatocyte regenerative response to partial hepatectomy in this model of acute liver injury, due to Cd intoxication.