The flavonoid monoHER prevents monocrotaline-induced hepatic sinusoidal injury in rats

Background: 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. Methods: 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. Results: 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. Conclusions: MonoHER prevented MCT induced portal hypertension and hepatic injury in rats. © 2012 Wiley Periodicals, Inc.