Froh M, Zhong Z, Walbrun P, Lehnert M, Netter S, Wiest R, Conzelmann L, Gäbele E, Hellerbrand C, Schölmerich J, Thurman RG. Dietary glycine blunts liver injury after bile duct ligation in rats. World J Gastroenterol 2008; 14(39): 5996-6003 [PMID: 18932277 DOI: 10.3748/wjg.14.5996]
Corresponding Author of This Article
Matthias Froh, Department of Internal Medicine I, University of Regensburg, Regensburg 93042, Germany. froh.science@mac.com
Article-Type of This Article
Basic Research
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World J Gastroenterol. Oct 21, 2008; 14(39): 5996-6003 Published online Oct 21, 2008. doi: 10.3748/wjg.14.5996
Dietary glycine blunts liver injury after bile duct ligation in rats
Matthias Froh, Zhi Zhong, Peter Walbrun, Mark Lehnert, Susanne Netter, Reiner Wiest, Lars Conzelmann, Erwin Gäbele, Claus Hellerbrand, Jürgen Schölmerich, Ronald G Thurman
Matthias Froh, Peter Walbrun, Susanne Netter, Reiner Wiest, Erwin Gäbele, Claus Hellerbrand, Jürgen Schölmerich, Department of Internal Medicine I, University of Regensburg, Regensburg 93042, Germany
Matthias Froh, Zhi Zhong, Mark Lehnert, Lars Conzelmann, Erwin Gäbele, Ronald G Thurman, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
Zhi Zhong, Department of Pharmaceutical Sciences, University of South Carolina, Charleston, South Carolina 29425, United States
Mark Lehnert, Department of Surgery, University of Frankfurt, Frankfurt am Main 60325, Germany
Lars Conzelmann, Department of Cardiothoracic and Vascular Surgery, University of Mainz, Mainz 55099, Germany
Author contributions: Froh M, Zhong Z, Schölmerich J and Thurman RG designed research; Froh M, Zhong Z, Walbrun P, Lehnert M and Netter S performed research; Froh M, Zhong Z, Conzelmann L and Gäbele E analyzed data; and Froh M, Hellerbrand C and Schölmerich J wrote the paper.
Supported by Grants from the National Institute of Alcohol Abuse and Alcoholism (NIAAA) and by a grant from the Deutsche Forschungsgemeinschaft, No. FR 1644/4-1
Correspondence to: Matthias Froh, Department of Internal Medicine I, University of Regensburg, Regensburg 93042, Germany. froh.science@mac.com
Telephone: +49-941-9447012 Fax: +49-941-9447011
Received: January 5, 2008 Revised: July 13, 2008 Accepted: July 20, 2008 Published online: October 21, 2008
Abstract
AIM: To investigate the effects of (dietary) glycine against oxidant-induced injury caused by bile duct ligation (BDL).
METHODS: Either a diet containing 5% glycine or a standard diet was fed to male Sprague-Dawley (SD) rats. Three days later, BDL or sham-operation was performed. Rats were sacrificed 1 to 3 d after BDL. The influence of deoxycholic acid (DCA) in the presence or absence of glycine on liver cells was determined by measurement of calcium and chloride influx in cultivated Kupffer cells and lactate dehydrogenase (LDH) activity was determined in the supernatant of cultivated hepatocytes.
RESULTS: Serum alanine transaminase levels increased to about 600 U/L 1 d after BDL. However, enzyme release was blunted by about two third in rats receiving glycine. Release of the alkaline phosphatase and aspartate aminotransferase was also blocked significantly in the group fed glycine. Focal necrosis was observed 2 d after BDL. Glycine partially blocked the histopathological changes. Incubation of Kupffer cells with DCA led to increased intracellular calcium that could be blocked by incubation with glycine. However, systemic blockage of Kupffer cells with gadolinium chloride had no effects on transaminase release. Incubation of isolated hepatocytes with DCA led to a significant release of LDH after 4 h. This release was largely blocked when incubation with glycine was performed.
CONCLUSION: These data indicate that glycine significantly decreased liver injury, most likely by a direct effect on hepatocytes. Kupffer cells do not appear to play an important role in the pathological changes caused by cholestasis.
