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Amino Acids

, Volume 40, Issue 4, pp 1139–1150 | Cite as

Dietary glycine protects from chemotherapy-induced hepatotoxicity

  • Saulius Mikalauskas
  • Laura Mikalauskiene
  • Helge Bruns
  • Arash Nickkholgh
  • Katrin Hoffmann
  • Thomas Longerich
  • Kestutis Strupas
  • Markus W. Büchler
  • Peter SchemmerEmail author
Original Article

Abstract

Hepatotoxic side effects of neoadjuvant chemotherapy for colorectal liver metastases increase perioperative morbidity and mortality. Glycine protects liver from injury in various animal models. Thus, this study was designed to assess its effect on liver after chemotherapy. Sprague–Dawley rats (200–220 g) were fed a synthetic diet containing 5% glycine for 5 days. Subsequently, chemotherapy (FOLFIRI: irinotecan, folinic acid and fluorouracil, or FOLFOX: oxaliplatin, folinic acid and fluorouracil) was administered at standard doses. Transaminases, histology, immunohistochemistry and in vivo microscopy were used to index liver injury, to monitor intrahepatic microperfusion and activation of Kupffer cells. Glycine significantly decreased transaminases after chemotherapy to 25–50% of control values (p < 0.05). Microvesicular steatosis was significantly reduced from 18.5 ± 3.4 and 57.1 ± 8.6% in controls to 9.5 ± 1.8 and 37.7 ± 4.4% after FOLFIRI and FOLFOX, respectively. Furthermore, phagocytosis of latex beads was reduced by about 50%, while leukocyte adherence in central and midzonal subacinar zones decreased to 60–80% after glycine (p < 0.05). Glycine significantly reduced expression of inducible nitric oxide synthase after chemotherapy, while hepatic microcirculation was increased (p < 0.05). This study shows for the first time that glycine reduces chemotherapy-induced liver injury. The underlying mechanisms most likely include Kupffer cells and an improved intrahepatic microperfusion.

Keywords

Glycine Chemotherapy Kupffer cell-dependent liver injury Steatosis In vivo microscopy Leukocyte–endothelium interaction 

Notes

Acknowledgments

The authors are grateful to Elvira Mohr for her kind help with sectioning liver tissue and histochemical staining, and to Martynas Manikas for excellent assistance with statistical evaluation. The authors would like to thank Markus Zorn for performing laboratory analyses of transaminases and Christa Flechtenmacher for supervision of immunohistochemistry.

Conflict of interest

No conflicts of interest exist

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Saulius Mikalauskas
    • 1
    • 3
  • Laura Mikalauskiene
    • 1
  • Helge Bruns
    • 1
  • Arash Nickkholgh
    • 1
  • Katrin Hoffmann
    • 1
  • Thomas Longerich
    • 2
  • Kestutis Strupas
    • 3
  • Markus W. Büchler
    • 1
  • Peter Schemmer
    • 1
    Email author
  1. 1.Department of General and Transplantation SurgeryRuprecht-Karls-University of HeidelbergHeidelbergGermany
  2. 2.Department of PathologyRuprecht-Karls-University of HeidelbergHeidelbergGermany
  3. 3.Center of Abdominal Surgery, Clinic of Gastroenterology, Nephrology, Urology and Abdominal SurgeryVilnius University Hospital Santariskiu KlinikosVilniusLithuania

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