Fig 1.
(A) Hydroxyproline content of Foxn1 nu/nu mice (left) and BALB/c mice (right) liver samples following TAA fibrosis induction. (B) alpha-SMA image analysis representing percentage of positive pixels of total area from immunofluorescent stained liver slides images. Weeks of recovery are indicated as +nw. Results are expressed as mean ± SE. (*P<0.05, **P<0.01, ***P<0.001)
Fig 2.
Histological features of liver fibrosis.
Masson’s trichrome stained livers from Foxn1 nu/nu mice (top) receiving (A) normal drinking water, (B) TAA drinking water [0.02%] for 4 weeks, (C) 8 weeks, (D) 12 weeks, (E) 16 weeks, (F) 2 and (G) 3 weeks of recovery after the 16 week treatment and from BALB/c mice (bottom) IP injected with (H) saline, (I) TAA [200 μg/g bw] for 12 weeks and (J) 2 weeks of recovery following the 12 week TAA treatment. Pictures were obtained at a 100X magnification. Arrows indicate fibrotic septae.
Fig 3.
Activation of hepatic stellate cells.
Histological alpha-SMA (green) immunofluorescent-stained livers from Foxn1 nu/nu mice (top) receiving (A) normal drinking water, (B) TAA drinking water [0.02%] for 4 weeks, (C) 8 weeks, (D) 12 weeks, (E) 16 weeks, (F) 16 weeks followed by 2 weeks or (G) 3 weeks of recovery and from BALB/c mice (bottom) IP injected with (H) saline or (I) TAA [200μg/g bw] for 12 weeks and (J) 2 weeks of recovery following TAA treatment. Nuclei were stained with Hoechst 33258 (blue). Microphotographs were obtained at a 100X magnification.
Fig 4.
COL1 mRNA expression and ERK1/2 phosphorylation.
(A) PreCol1a1 mRNA relative expression qPCR of Foxn1 nu/nu (left) and BALB/c mice (right) liver samples following induction of fibrosis and (B) ERK1/2 phosphorylation by Western blot of Foxn1 nu/nu (left) and BALB/c mice (right) liver samples following TAA fibrosis induction with associated representative pictures. Number of weeks of recovery is indicated as +nw. Results are expressed as mean ± SE. (*P<0.05, **P<0.01)
Fig 5.
Protective effect of liver fibrosis in Foxn1 nu/nu mice against different cytotoxic agents.
Dosage of serum AST and ALT levels from fibrotic Foxn1 nu/nu mice after TAA administration through drinking water [0.02%] for 16 weeks while non-fibrotic mice received normal drinking water (H2O). Cytotoxic agents were injected IP: CCl4 [0.5 mL/kg bw] (sacrificed 24 hours following injection), Fas Jo2 antibody [0.5μg/g bw] (sacrificed 6 hours following injection) and APAP [750 mg/kg bw] (sacrifice 6 hours after injection). Results are expressed as mean ± SE. (*P<0.05, **P<0.01, ***P<0.001)
Fig 6.
Histological features of hepatoprotective effect of liver fibrosis to cytotoxic agents.
HPS-stained liver slices of Foxn1 nu/nu mice injected with the following cytotoxic agents: CCl4 [0.5 mL/kg bw] in (A) non-fibrotic and (B) fibrotic mice (16 weeks of TAA in drinking water [0.02%] (sacrificed 24 hours following TAA treatment); Fas Jo2 antibody [0.5 μg/g bw] in (C) non-fibrotic and (D) fibrotic mice (sacrificed 6 hours following TAA treatment); and APAP [750 mg/kg bw] in (E) non-fibrotic and (F) fibrotic mice (sacrificed 6 hours following TAA treatment). Representative microphotographs were obtained at a 100X magnification. Arrows indicate parenchymal red blood cell infiltration and/or necrosis.