Department of General and Transplantation Surgery, Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany.
Amino Acids. 2011 Apr;40(4):1139-50. doi: 10.1007/s00726-010-0737-6. Epub 2010 Sep 18.
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.
结直肠癌肝转移新辅助化疗的肝毒性副作用增加围手术期发病率和死亡率。甘氨酸在各种动物模型中可保护肝脏免受损伤。因此，本研究旨在评估其对化疗后肝脏的作用。Sprague-Dawley 大鼠（200-220 g）喂食含有 5%甘氨酸的合成饮食 5 天。随后，以标准剂量给予化疗（FOLFIRI：伊立替康、亚叶酸和氟尿嘧啶，或 FOLFOX：奥沙利铂、亚叶酸和氟尿嘧啶）。使用转氨酶、组织学、免疫组织化学和体内显微镜检查来评估肝损伤，监测肝内微灌注和库普弗细胞的激活。甘氨酸可显著降低化疗后转氨酶至对照值的 25-50%（p < 0.05）。微泡性脂肪变性分别从对照值的 18.5 ± 3.4%和 57.1 ± 8.6%显著减少至 FOLFIRI 和 FOLFOX 后的 9.5 ± 1.8%和 37.7 ± 4.4%。此外，乳胶珠的吞噬作用减少了约 50%，而白细胞在中央和中区亚区带的粘附减少到 60-80%甘氨酸后（p < 0.05）。甘氨酸可显著降低化疗后诱导型一氧化氮合酶的表达，同时增加肝微循环（p < 0.05）。本研究首次表明甘氨酸可减轻化疗引起的肝损伤。其潜在机制可能包括库普弗细胞和改善的肝内微灌注。
