UEG Week 2016 Poster Presentations

Abstract

Contact E-mail Address: nakuraokura0922@yahoo.co.jp.IntroductionSinusoidal obstruction syndrome (SOS) is a drug-induced liver injury caused by anticancer treatments, such as oxaliplatin-based chemotherapy. Injury of sinusoidal endothelial cells (SECs) and subsequent extravasated platelet aggregation (EPA) initiate development of SOS. Beraprost sodium (BPS) has a protective effect on SECs and antiplatelet effect. The aim of this study was to examine the protective effect of BPS against SECs injury resulting from monocrotaline (MCT)-induced SOS in mice.Aims & MethodsSOS was induced in Crl:CD1 (ICR) mice by intraperitoneal administration of MCT (270 mg/kg). To evaluate the effect of BPS on SOS, the mice were divided into two groups. In the BPS group, BPS (200 μl/kg) was injected by intraperitoneal administration at 1 hour before, 3 hours after, and 9 hours after MCT administration. The control group received intraperitoneal injections of the same volume of saline at the same time points. All mice were sacrificed at 48 hours after MCT administration and the protective effect on SECs was assessed by determining blood cell count, serum biochemical findings and immunohistochemical stains of sinusoidal endothelial cell antibody (SEC-1) and CD62P (P-selectin). Western blot analysis and real-time polymerase chain reaction (RT-PCR) were also used to examine plasminogen activator inhibitor-1 (PAI-1) and endothelial nitric oxide synthase (eNOS) expression.ResultsPlatelet count was maintained in the BPS group compared to that in the MCT group (48.2 vs. 4.8 ´104/μl, P < 0.001). Serum transaminase levels and hyaluronic acid (HA) in the BPS group were significantly reduced compared to the levels in the MCT group (AST 129 vs. 1013 IU/L, P < 0.05; ALT 90 vs. 923 IU/L, P < 0.01; HA 670 vs. 2243 ng/mL, P < 0.01). In the MCT group, liver histology showed endothelial damage of the central venule, congestion and obstruction of the sinusoids, and necrosis of hepatocytes in zone 3. In the BPS group, these findings were suppressed. Immunohistochemistry showed a protective effect of SECs on SEC-1 and a decrease in platelet infiltration in the space of Disse on CD62P in the BPS group compared to that in the MCT group. Expression of PAI-1 was significantly lower and expression of eNOS was significantly higher in the BPS group.ConclusionBPS preserved SECs and suppressed the progression of MCT-induced SOS in mice, suggesting that BPS is useful for the prevention of SOS.Disclosure of InterestAll authors have declared no conflicts of interest.