Up-regulation of Nrf2 and HO-1 following successive subcutaneous treatments with lansoprazole.

<p>A) No significant changes in the levels of mRNA for Nrf2, Keap1 and HO-1. B) Up-regulation of IR levels for Nrf2 and HO-1, with no change of Keap1 IR. *P<0.05, ***P<0.001 compared with control. Representative photographs showing an increase of Nrf2 and HO-1 IR. C) Nuclear translocation of Nrf2 in hepatocytes as demonstrated by double fluorescence immunohistochemistry and western blotting of cytosol fraction (C; Calpain-positive) and nuclear fraction (N; Histone H1-positive). Blue indicates DAPI-positive nuclei, red indicates Nrf2 IR, and pink indicates the nuclear localization of Nrf2. Bar = 20 µm.</p

Up-regulation of mRNA for Nrf2-dependent antioxidant and phase II enzymes following single oral treatment with lansoprazole.

<p>A) Up-regulation of HO-1 mRNA in the liver at 3 h. B) Up-regulation of NAD (P) H dehydrogenase, quinone 1 (Nqo1) mRNA in the liver at 3 h. C) Up-regulation of glutathione S-transferase A2 (Gsta2) mRNA in the liver at 3 h. D) Up-regulation of UDP glucuronosyltransferase 1 family polypeptide A6 (Ugt1a6) mRNA in the liver at 3 h. *P<0.05, ** P<0.01, ***P<0.001 compared with control.</p

Figure 9

<p>A summary schematic of the lansoprazole-induced AhR/Cyp1a1/Nrf2 pathway in the liver. XRE, xenobiotic response elements; ARE, antioxidant response element.</p

Histology of the liver stained with hematoxylin-eosin.

<p>A) Control (group A). B) TAA-treated liver (group C). C) TAA-treated liver pretreated by lansoprazole (group D), Bar = 250 µm. D) Lesion index (%). * P<0.05.</p

Up-regulation of HO-1 IR in hepatocytes following single oral treatment with lansoprazole.

<p>A) Up-regulation of HO-1 IR in the liver at 6 h. ** P<0.01 compared with control. Representative photographs showing an increase of HO-1 IR. B) Immunohistochemistry for HO-1 in the liver at 6 h. Signals for HO-1 IR were detected in macrophages in the control. <i>De novo</i> signals for HO-1 IR were observed in hepatocytes in response to treatment with lansoprazole. Upper panel bar = 100 µm. Lower panel bar = 20 µm.</p

Up-regulation and nuclear translocation of Nrf2 in the liver following single oral treatment with lansoprazole.

<p>A) Up-regulation of Nrf2 mRNA in the liver at 3 h. ** P<0.01, ***P<0.001 compared with control. B) Up-regulation of Nrf2 immunoreactivity (IR) in the liver at 6 h. *P<0.05, ** P<0.01 compared with control. Representative photographs showing an increase of Nrf2 IR. C) No significant changes in Keap1 mRNA levels in the liver at 3 h. D) No significant changes in Keap1 IR levels in the liver at 6h. Representative photographs showing no change of Keap1 IR. E) Nuclear translocation of Nrf2 in the liver demonstrated by western blotting of cytosol fraction (C; Calpain-positive) and nuclear fraction (N; Histone H1-positive) at 3h and 6h. F) Nuclear translocation of Nrf2 in hepatocytes as demonstrated by double fluorescence immunohistochemistry. Blue indicates DAPI-positive nuclei, red indicates Nrf2 IR, and pink indicates the nuclear localization of Nrf2. Bar = 20 µm.</p

Lansoprazole inducing networks.

<p>Lansoprazole inducing networks.</p

Serum levels and the % inhibition of AST and ALT in TAA-induced acute hepatic damage.

<p>A) Serum AST levels. * P<0.001 compared with group A (control). B) Serum ALT levels * P<0.0001 compared with group A (control). # P<0.01 compared with group C (acute hepatic damage). C) The % inhibition of TAA-induced increase of serum AST levels between group D (acute hepatic damage with lansoprazole) and group F (acute hepatic damage with lansoprazole and SnMP). D) The % inhibition of TAA-induced increase of serum ALT levels between group D (acute hepatic damage with lansoprazole) and group F (acute hepatic damage with lansoprazole and SnMP).</p

Validation of gene expression changes in the liver at 3 h following oral administration of lansoprazole (100 mg/kg).

<p>A) Up-regulation of AhR mRNA. ***P<0.0001. B) No significant change (P = 0.068) of Pparα mRNA levels. C) Up-regulation of Cyp1a1 mRNA. ***P<0.0001.</p