Article
Glycine protects from chemotherapy-induced hepatotoxicity
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Published: | April 16, 2008 |
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Introduction: Hepatotoxic side effects of chemotherapy for colorectal liver metastases increase perioperative morbidity and mortality after liver resection. Glycine has been shown to possess hepatoprotective effects in various animal models. Thus, this study was designed to assess its effect on liver after chemotherapy.
Material and methods: Sprague-Dawley rats (200 – 220 g) received a 5 % glycine or a control diet for 5 days. Subsequently, chemotherapy (FOLFIRI - irinotecan, folinic acid, and fluoruracil) was administered at standard doses. Transaminases, histology and in vivo microscopy were used to index hepatic injury, to monitor microperfusion, and activation of Kupffer cells. Analysis of variance (ANOVA) followed by t test were used as appropriate. Results are presented as mean±SEM.
Results: Glycine resulted in significantly lower values of both AST and ALT at different time points within 24 hours after the end of chemotherapeutic regimens to 25-50 % of control values (p<0.05). Microvesicular steatosis was reduced from 18.5±3.4 % in controls to 9.5±1.8 % in glycine group (p<0.05). Furthermore, in vivo microscopy documented a 50 % reduction in phagocytosis of latex beads as well as an 60-80 % reduction in leukocyte adherence in central and midzonal subacinar zones with glycine (p<0.05).
Conclusion: This study shows for the first time that glycine reduces chemotherapy-induced liver damage. The underlying mechanisms most likely include inactivation of Kupffer cells, reduced steatotic changes, and improvement in hepatic microcirculation.