UCL Hepatology, Department of HPB and Liver Transplantation Surgery, University College London Medical School, Royal Free Campus, London, UK.
J Surg Oncol. 2012 Jul 1;106(1):72-8. doi: 10.1002/jso.23046. Epub 2012 Jan 27.
Sinusoidal obstruction syndrome (SOS) occurs in 50-70% of patients after oxaliplatin treatment for hepatic colorectal metastasis. SOS is associated with portal hypertension and is caused by oxidative damage to endothelial cells and matrix metalloproteinase (MMP) induction. We studied the effect of a flavonoid (monoHER) on SOS prevention.
A monocrotaline (MTC) SOS model was used in rats, with pre-treatment of monoHER. We studied hepatocellular damage and MMP expression. The potential inhibition of oxaliplatin cytotoxicity by monoHER was tested in vitro in colorectal cancer cell lines.
MonoHER ameliorated the increase in portal pressure after MCT (72 hr: 7.3 ± 2.7 mmHg vs. 11.4 ± 3.0 mmHg, P = 0.016 MCT + monoHER vs. MCT, P < 0.01). MonoHER prevented hepatocellular damage (ALT: 48 hr 42.2 ± 3.1 IU/L vs. 253.4 ± 171.7 IU/L, P = 0.034; 72 hr: 46.2 ± 4.3 IU/L vs. 311.9 ± 163.6 IU/L, MCT + monoHER vs. MCT, P < 0.01). The liver damage score was lower in the monoHER group (72 hr: 4.8 ± 3.6 vs. 10.3 ± 0.5, MCT-monoHER vs. MCT, P < 0.01) associated with less inflammatory cell infiltration. Livers of MCT treated rats had higher expression of MMP-9 when compared to monoHER pairs at 24 hr (P = 0.016) and 72 hr (P < 0.001). MonoHER had no effect on in vitro proliferation of colorectal cancer cells when used either alone or in combination with oxaliplatin.
MonoHER prevented MCT induced portal hypertension and hepatic injury in rats.
奥沙利铂治疗肝转移性结直肠癌后，50-70%的患者会发生窦状隙阻塞综合征（SOS）。SOS 与门脉高压有关，是由内皮细胞氧化损伤和基质金属蛋白酶（MMP）诱导引起的。我们研究了黄酮类化合物（monoHER）对 SOS 预防的作用。
采用野百合碱（MTC）SOS 大鼠模型，进行 monoHER 预处理。我们研究了肝细胞损伤和 MMP 表达。在体外结直肠癌细胞系中检测了 monoHER 对奥沙利铂细胞毒性的潜在抑制作用。
MonoHER 改善了 MCT 后门静脉压力的升高（72 小时：7.3±2.7mmHg 比 11.4±3.0mmHg，P=0.016 MCT+monoHER 比 MCT，P<0.01）。MonoHER 防止了肝细胞损伤（ALT：48 小时 42.2±3.1IU/L 比 253.4±171.7IU/L，P=0.034；72 小时 46.2±4.3IU/L 比 311.9±163.6IU/L，MCT+monoHER 比 MCT，P<0.01）。MonoHER 组的肝损伤评分较低（72 小时：4.8±3.6 比 10.3±0.5，MCT+monoHER 比 MCT，P<0.01），炎症细胞浸润也较少。与 monoHER 配对相比，MTC 治疗大鼠肝脏在 24 小时（P=0.016）和 72 小时（P<0.001）时 MMP-9 的表达更高。MonoHER 单独或与奥沙利铂联合使用时，对结直肠癌细胞的体外增殖均无影响。
MonoHER 预防了 MTC 诱导的大鼠门脉高压和肝损伤。
