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SHR Neuro Krebs Kardio Lipid

Mikalauskas, S; Mikalauskiene, L; Bruns, H; Nickkholgh, A; Hoffmann, K; Longerich, T; Strupas, K; Büchler, MW; Schemmer, P.
Dietary glycine protects from chemotherapy-induced hepatotoxicity.
Amino Acids. 2011; 40(4):1139-1150
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Autor/innen der Med Uni Graz:
Schemmer Peter
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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.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - adverse effects
Camptothecin - administration & dosage
Camptothecin - adverse effects
Camptothecin - analogs & derivatives
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - mortality
Colorectal Neoplasms - pathology
Dietary Supplements -
Drug-Induced Liver Injury - metabolism
Drug-Induced Liver Injury - pathology
Drug-Induced Liver Injury - prevention & control
Drug-Related Side Effects and Adverse Reactions - prevention & control
Fatty Liver - etiology
Fatty Liver - metabolism
Fatty Liver - pathology
Fatty Liver - prevention & control
Female -
Fluorouracil - administration & dosage
Fluorouracil - adverse effects
Glycine - administration & dosage
Immunohistochemistry -
Kupffer Cells - pathology
Leucovorin - administration & dosage
Leucovorin - adverse effects
Liver - drug effects
Liver - metabolism
Liver - pathology
Microcirculation -
Neoadjuvant Therapy - adverse effects
Nitric Oxide Synthase Type II - analysis
Organoplatinum Compounds - administration & dosage
Organoplatinum Compounds - adverse effects
Phagocytosis -
Rats -
Rats, Sprague-Dawley -
Transaminases - analysis

Find related publications in this database (Keywords)
Glycine
Chemotherapy
Kupffer cell-dependent liver injury
Steatosis
In vivo microscopy
Leukocyte-endothelium interaction
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