OBJECTIVE: To explore putative cytoprotective functions of biliverdin during hepatic ischemia/reperfusion (I/R) injury in rat models. MATERIAL AND METHODS: Male Sprague Dawley (SD) rat livers were harvested and stored for 24 hours at 4 degrees C in University of Wisconsin (UW) solution (n=18), and then perfused with blood for 2 hours on an isolated rat liver perfusion apparatus equipped for temperature (37 degrees C), pressure (13 cm H2O), and pH (7.3) maintenance. Biliverdin was added to the blood at concentrations of 10 and 50 micromol in two groups of six animals. Portal vein blood flow, bile production, and GOT/GPT levels were assessed serially. At the conclusion of the experiment, liver samples were collected for histologic evaluation using Suzuki criteria. RESULTS: BV exerted protective effects against liver I/R injury. Adjunctive biliverdin improved portal venous blood flow (mL/min/g) from the beginning of reperfusion (1.33+/-0.17 versus 0.98+/-0.15; P<.001) and increased bile production (mL/g) as compared with the control group (3.40 versus 1.88; P<.003). I/R-induced hepatocellular damage as measured by GOT/GPT release (IU/L) was diminished in the biliverdin group (91 versus 171 and 46 versus 144, respectively; P<.0001). Improved liver function by biliverdin was accompanied by preservation of the histologic structure as assessed by Suzuki criteria (3.7+/-1.4 versus 6.8+/-0.8 in untreated controls; P<.005). CONCLUSIONS: Biliverdin attenuates the ischemia/early reperfusion injury of rat liver grafts as assessed by hemodynamics, function, enzyme analysis, and histology. This study provides the rationale for novel therapeutic approaches using biliverdin to maximize the organ donor pool through the safer use of liver transplants despite prolonged periods of cold ischemia.
OBJECTIVE: To explore putative cytoprotective functions of biliverdin during hepatic ischemia/reperfusion (I/R) injury in rat models. MATERIAL AND METHODS: Male Sprague Dawley (SD) rat livers were harvested and stored for 24 hours at 4 degrees C in University of Wisconsin (UW) solution (n=18), and then perfused with blood for 2 hours on an isolated rat liver perfusion apparatus equipped for temperature (37 degrees C), pressure (13 cm H2O), and pH (7.3) maintenance. Biliverdin was added to the blood at concentrations of 10 and 50 micromol in two groups of six animals. Portal vein blood flow, bile production, and GOT/GPT levels were assessed serially. At the conclusion of the experiment, liver samples were collected for histologic evaluation using Suzuki criteria. RESULTS: BV exerted protective effects against liver I/R injury. Adjunctive biliverdin improved portal venous blood flow (mL/min/g) from the beginning of reperfusion (1.33+/-0.17 versus 0.98+/-0.15; P<.001) and increased bile production (mL/g) as compared with the control group (3.40 versus 1.88; P<.003). I/R-induced hepatocellular damage as measured by GOT/GPT release (IU/L) was diminished in the biliverdin group (91 versus 171 and 46 versus 144, respectively; P<.0001). Improved liver function by biliverdin was accompanied by preservation of the histologic structure as assessed by Suzuki criteria (3.7+/-1.4 versus 6.8+/-0.8 in untreated controls; P<.005). CONCLUSIONS:Biliverdin attenuates the ischemia/early reperfusion injury of rat liver grafts as assessed by hemodynamics, function, enzyme analysis, and histology. This study provides the rationale for novel therapeutic approaches using biliverdin to maximize the organ donor pool through the safer use of liver transplants despite prolonged periods of cold ischemia.
Authors: Barbara Wegiel; David Gallo; Eva Csizmadia; Thierry Roger; Elzbieta Kaczmarek; Clair Harris; Brian S Zuckerbraun; Leo E Otterbein Journal: Proc Natl Acad Sci U S A Date: 2011-10-31 Impact factor: 11.205
Authors: Niteen Tapuria; Sameer P Junnarkar; Neelanjana Dutt; Mahmoud Abu-Amara; Barry Fuller; Alexander M Seifalian; Brian R Davidson Journal: HPB (Oxford) Date: 2009-03 Impact factor: 3.647
Authors: Giovanni Li Volti; David Sacerdoti; Claudia Di Giacomo; Maria-Luisa Barcellona; Antonio Scacco; Paolo Murabito; Antonio Biondi; Francesco Basile; Diego Gazzolo; Raul Abella; Alessandro Frigiola; Fabio Galvano Journal: World J Gastroenterol Date: 2008-10-28 Impact factor: 5.742
Authors: Barbara Wegiel; Catherine J Baty; David Gallo; Eva Csizmadia; Jeffrey R Scott; Ardavan Akhavan; Beek Y Chin; Elzbieta Kaczmarek; Jawed Alam; Fritz H Bach; Brian S Zuckerbraun; Leo E Otterbein Journal: J Biol Chem Date: 2009-06-09 Impact factor: 5.157