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Article

Extravasated platelet aggregation in the livers of rats with drug‑induced hepatic sinusoidal obstruction syndrome

  • Authors:
    • Miki Hirata
    • Hidehiro Tajima
    • Tomoharu Miyashita
    • Takashi Miyata
    • Shinichi Nakanuma
    • Isamu Makino
    • Hironori Hayashi
    • Katsunobu Oyama
    • Hiroyuki Takamura
    • Itasu Ninomiya
    • Sachio Fushida
    • Hiroki Nakata
    • Shoichi Iseki
    • Shinichi Harada
    • Tomohiko Wakayama
    • Tetsuo Ohta
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920‑8641, Japan, Department of Histology and Embryology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920‑8641, Japan, Center of Biochemical Research, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920‑8641, Japan, Department of Histology, Faculty of Life Sciences, Kumamoto University, Kanazawa, Ishikawa 920‑8641, Japan
  • Pages: 3147-3152
    |
    Published online on: March 28, 2017
       https://doi.org/10.3892/mmr.2017.6407
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Abstract

Oxaliplatin-based chemotherapy plays an important role in the treatment of colorectal liver metastases. Oxaliplatin, however, causes sinusoidal obstruction syndrome (SOS), which is characterized by portal hypertension, splenomegaly, thrombocytopenia, and liver dysfunction. SOS is diagnosed histopathologically by disruption of the sinusoidal endothelium, collagen deposition, fibrosis especially around zone 3, dilatation of the sinusoidal space and congestion. This study assessed the characteristics of a rat model of SOS. SOS was induced in rats by administration of monocrotaline (MCT). Blood chemistries and macroscopic and microscopic findings were compared in rats administered MCT and vehicle (control group). Levels of expression in the liver of CD41, P‑selectin, rat endothelial cell antigen‑1, CD34, and cleaved caspase‑3 were analyzed immunohistochemically. Moreover, livers of these rats were analyzed by electron microscopy. Macroscopically, MCT‑treated rats showed accumulation of bloody ascites and blue liver and were diagnosed with SOS histologically. Serum concentrations of aspartate aminotransferase (P=0.003), alanine aminotransferase (P=0.008), total‑bilirubin (P=0.012), direct‑bilirubin (P=0.007), indirect‑bilirubin (P=0.003), lactate dehydrogenase (P<0.001) and hyaluronic acid (P=0.016) were significantly higher, and platelet counts significantly lower (P=0.004), in MCT‑treated than in control rats. The livers of MCT‑treated rats were immunohistochemically positive for CD41 and P‑selectin, suggesting platelet aggregates; for rat endothelial cell antigen‑1 and CD34, suggesting sinusoidal endothelial disorder; and for cleaved caspase‑3, suggesting hepatocyte apoptosis. Electron microscopic findings revealed platelet aggregation in the space of Disse in the MCT group. Extravasated platelet aggregation in Disse's space may be involved in the development of SOS.
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Copy and paste a formatted citation
Spandidos Publications style
Hirata M, Tajima H, Miyashita T, Miyata T, Nakanuma S, Makino I, Hayashi H, Oyama K, Takamura H, Ninomiya I, Ninomiya I, et al: Extravasated platelet aggregation in the livers of rats with drug‑induced hepatic sinusoidal obstruction syndrome. Mol Med Rep 15: 3147-3152, 2017.
APA
Hirata, M., Tajima, H., Miyashita, T., Miyata, T., Nakanuma, S., Makino, I. ... Ohta, T. (2017). Extravasated platelet aggregation in the livers of rats with drug‑induced hepatic sinusoidal obstruction syndrome. Molecular Medicine Reports, 15, 3147-3152. https://doi.org/10.3892/mmr.2017.6407
MLA
Hirata, M., Tajima, H., Miyashita, T., Miyata, T., Nakanuma, S., Makino, I., Hayashi, H., Oyama, K., Takamura, H., Ninomiya, I., Fushida, S., Nakata, H., Iseki, S., Harada, S., Wakayama, T., Ohta, T."Extravasated platelet aggregation in the livers of rats with drug‑induced hepatic sinusoidal obstruction syndrome". Molecular Medicine Reports 15.5 (2017): 3147-3152.
Chicago
Hirata, M., Tajima, H., Miyashita, T., Miyata, T., Nakanuma, S., Makino, I., Hayashi, H., Oyama, K., Takamura, H., Ninomiya, I., Fushida, S., Nakata, H., Iseki, S., Harada, S., Wakayama, T., Ohta, T."Extravasated platelet aggregation in the livers of rats with drug‑induced hepatic sinusoidal obstruction syndrome". Molecular Medicine Reports 15, no. 5 (2017): 3147-3152. https://doi.org/10.3892/mmr.2017.6407
Copy and paste a formatted citation
x
Spandidos Publications style
Hirata M, Tajima H, Miyashita T, Miyata T, Nakanuma S, Makino I, Hayashi H, Oyama K, Takamura H, Ninomiya I, Ninomiya I, et al: Extravasated platelet aggregation in the livers of rats with drug‑induced hepatic sinusoidal obstruction syndrome. Mol Med Rep 15: 3147-3152, 2017.
APA
Hirata, M., Tajima, H., Miyashita, T., Miyata, T., Nakanuma, S., Makino, I. ... Ohta, T. (2017). Extravasated platelet aggregation in the livers of rats with drug‑induced hepatic sinusoidal obstruction syndrome. Molecular Medicine Reports, 15, 3147-3152. https://doi.org/10.3892/mmr.2017.6407
MLA
Hirata, M., Tajima, H., Miyashita, T., Miyata, T., Nakanuma, S., Makino, I., Hayashi, H., Oyama, K., Takamura, H., Ninomiya, I., Fushida, S., Nakata, H., Iseki, S., Harada, S., Wakayama, T., Ohta, T."Extravasated platelet aggregation in the livers of rats with drug‑induced hepatic sinusoidal obstruction syndrome". Molecular Medicine Reports 15.5 (2017): 3147-3152.
Chicago
Hirata, M., Tajima, H., Miyashita, T., Miyata, T., Nakanuma, S., Makino, I., Hayashi, H., Oyama, K., Takamura, H., Ninomiya, I., Fushida, S., Nakata, H., Iseki, S., Harada, S., Wakayama, T., Ohta, T."Extravasated platelet aggregation in the livers of rats with drug‑induced hepatic sinusoidal obstruction syndrome". Molecular Medicine Reports 15, no. 5 (2017): 3147-3152. https://doi.org/10.3892/mmr.2017.6407
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