1. Volume 120, Issue 5, Pages 1227-1240 (April 2001)
Carbon monoxide from heme catabolism protects against hepatobiliary dysfunction in endotoxin-treated rat liver 
Takanori Kyokane, Shinji Norimizu, Hisashi Taniai, Tokio Yamaguchi, Shinji Takeoka, Eishun Tsuchida, Makoto Naito, Yuji Nimura, Yuzuru Ishimura, Makoto Suematsu 
Gastroenterology 
Volume 120, Issue 5, Pages (April 2001)
DOI: /gast
Copyright © 2001 American Gastroenterological Association Terms and Conditions

2. Fig. 1
Overproduction of NO and CO through iNOS and HO-1 in livers undergoing LPS exposure. (A) Western blotting analyses showing effects of LPS on expression of iNOS and HO-1. m, molecular markers; LDD(+), Kupffer cell–depleting procedure by LDD. (B) Measurements of NO2− and CO in the venous perfusate and bilirubin (BR)-IXα in bile collected from LPS-treated livers. ▨, Data collected from livers perfused with 5 mmol/L AG, an inhibitor of iNOS. Note that the AG treatment completely attenuated LPS-induced overproduction of NO and inversely increased generation of CO and BR-IXα (†P < 0.05). #P < 0.05 compared with the 6-hour LPS-treated group. Data indicate mean ± SD of measurements from 5–7 livers.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

3. Fig. 2
Effects of HbO2, metHb, and HbV-O2 on the vascular resistance and tissue cGMP contents in the (left) LPS-untreated and (right) -treated livers. Shaded area indicates a 15-minute interval for perfusion with the Hb derivatives. The cGMP contents were measured in snap-frozen tissue samples collected at 15 minutes (arrows in the upper panels), the end of perfusion with the reagents. *P < 0.05 compared with the baseline in the LPS-untreated control. †P < 0.05 compared with the data from livers untreated with Hb derivatives in the same panel. #P < 0.05 compared with the data in the Hb-perfused LPS livers. Data indicate mean ± SD of measurements from 5–7 livers.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

4. Fig. 3
Effects of HbO2, metHb, and HbV-O2 on the baseline bile output and biliary flux of bilirubin (BR)-IXα in the (left) LPS-untreated and (right) -treated livers. Shaded area indicates a 15-minute interval for perfusion with the Hb derivatives. Insets in the lower panels illustrate net increases in the biliary BR-IXα flux during the 15-minute period for perfusion of the Hb derivatives (ΔBF(15)BR-IXα). *P < 0.05 compared with the baseline in the LPS-untreated control. †P < 0.05 compared with the data from livers untreated with Hb derivatives in the same panel. #P < 0.05 compared with the data in the Hb-perfused LPS livers. Data indicate mean ± SD of measurements from 5–7 livers.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

5. Fig. 4
Effects of depletion of Kupffer cells on biliary flux of bilirubin (BR)-IXα in the LPS-pretreated liver. LDD(−)/(+) indicate the livers treated without and with LDD, the Kupffer cell–depleting reagent, respectively. Upper panels indicate representative microfluorographs showing phagocytosis of Nile red–coated latex particles in the 6-hour LPS-treated rats. Bar = 30 μm. The BR-IXα values were measured at 30 minutes after the onset of perfusion with the Hb derivatives, indicating mean ± SD of 6 and 4 experiments in the LDD(−) and LDD(+) groups, respectively. Note that the Kupffer cell depletion significantly attenuated the HbV-O2–induced elevation of BR-IXα (*P < 0.05), but not that induced by HbO2 or by metHb.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

6. Fig. 5
Effects of suppression of vasorelaxing gases by AG and ZnPP on the (A) vascular resistance and (B) bile output in the LPS-pretreated livers. Shaded area indicates a 10-minute period for perfusion of 300 nmol/L ZnPP and/or 4 μmol/L CO, or that of SNAP. Inset in the upper panel illustrates differences in tissue contents of cGMP among data points indicated by a–d (*P < 0.05 compared with a; †P < 0.05 compared with b). *P < 0.05 compared with the baseline value at 0 minutes. †P < 0.05 compared with the data measured at 30 minutes. #P < 0.05 compared with the data in the group treated with ZnPP. Data indicate mean ± SD of measurements from 5–7 livers.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

7. Fig. 6
Representative pictures showing patterns of sodium fluorescein labeling in perfused livers undergoing 6-hour LPS treatment. (A) The LPS-untreated control liver. (B) The liver exposed to 6-hour LPS treatment. (C and D) The LPS-treated liver perfused with 1.5 g/dL of HbO2 and metHb, respectively. Note that the HbO2 treatment induces a marked reduction of the fluorescence labeling in periportal regions. P, periportal regions; C, central venules. Bar = 100 μm.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

8. Fig. 7
Vasorelaxing effects of cytochrome P450 inhibitors, CTZ and metyrapone (MP), on the AG-elicited vasoconstriction in the LPS liver. (Left) Dose-dependent vasorelaxation by supplementation of CO. Note that 8 μmol/L CO induced a maximum vasorelaxation. (Right) Vasorelaxing effects of MP and CTZ. As seen, CO supplementation at 4 μmol/L does not induce additive relaxing effects in the presence of 10 μmol/L CTZ. *P < 0.05 and #P < 0.05 compared with the nontreating baseline (none). Data indicate mean ± SD of measurements from 5 livers.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

9. Fig. 8
Effects of administration of HbO2 and metHb on basal bile output and biliary bilirubin (BR)-IXα flux in LPS-treated rats in vivo. Alterations in bile output were expressed as percentage changes in the output measured at 20 minutes vs. that measured before the administration of HbO2 or metHb (%ΔBile output). ΔBR-IXα flux denotes net increases in BR-IXα excreted into bile during the initial 20 minutes after the administration of HbO2 or metHb was started. Data collected from the (A) LPS-untreated control rats and (B) those undergoing the 6-hour LPS exposure, respectively. *P < 0.05 compared with the value of the vehicle-treated LPS rats. †P < 0.05 compared with the values in the HbO2-treated LPS rats. Data indicate mean ± SD of measurements from 5–7 experiments.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions