Sinusoidal obstruction syndrome induced by monocrotaline in a large animal experiment – a pilot study
Authors:
R. Pálek 1,2; V. Liška 1,2; V. Třeška 1; J. Rosendorf 1; M. Emingr 1
; V. Tégl 2; A. Králíčková 3; K. Bajcurová 4; M. Jiřík 2; Z. Tonar 3
Authors place of work:
Chirurgická klinika, Univerzita Karlova, Lékařská fakulta v Plzni, Fakultní nemocnice Plzeň
1; Biomedicínské centrum, Lékařská fakulta Univerzity Karlovy v Plzni
2; Ústav histologie a embryologie, Lékařská fakulta Univerzity Karlovy v Plzni
3; Klinika zobrazovacích metod, Lékařská fakulta Univerzity Karlovy v Plzni
4
Published in the journal:
Rozhl. Chir., 2018, roč. 97, č. 5, s. 214-221.
Category:
Original articles
Summary
Introduction:
Sinusoidal obstruction syndrome (SOS) is a disease which is caused by toxic injury to hepatic sinusoids. This syndrome is most frequently caused by myeloablative radiochemotherapy in patients before hematopoietic stem cells transplantation and also by oxaliplatin mainly in patients with colorectal liver metastases. The aim of this study was to establish a large animal model of SOS, which would enable further study of this disease and facilitate translation of experimental outcomes into human medicine.
Methods:
A total of 27 domestic pigs (Prestice Black-Pied pig) were involved in this study (12 females). A group with a higher dose of monocrotaline (180 mg/kg) included 5 animals, and the remaining 22 pigs formed another group with a lower dose (36 mg/kg). Monocrotaline was administered via the portal vein and one week after the administration, partial hepatectomy of the left lateral liver lobe was performed. The animals were followed up for 3 weeks after monocrotaline administration. Regular ultrasound examinations were performed as well as examination of biochemical markers of liver and kidney functions and histological examination of liver parenchyma samples.
Results:
The features of toxic liver injury which we observed in case of all animals were comparable with macroscopic and microscopic appearance of SOS. We recorded AST, ALT, bilirubin and ammonia elevation after monocrotaline administration. Echogenicity on ultrasound images of injured liver parenchyma was higher compared to echogenicity of healthy parenchyma. All the five animals from the first group with a higher monocrotaline dose had died before partial hepatectomy (1st–3rd day after monocrotaline administration). Death before partial hepatectomy occurred in 3 cases (6th and 7th day after monocrotaline administration) in the second group of 22 animals with a lower dose of monocrotaline. Death after partial hepatectomy occurred in 8 cases (7th–17th day after moncrotaline administration) in the same group. 11 animals survived the entire experimental period. The cause of death (in both groups) was metabolic failure in 10 animals and exsanguination in 4 animals, both due to severe hepatopathy. Death of 2 animals was not associated with monocrotaline intoxication (strangulation of small intestine, gastrectasis).
Conclusions:
We established a large animal model of SOS induced by monocrotaline administration (36 mg/kg via portal vein). This model can contribute to research of therapeutic modalities for this disease or to evaluation of surgical treatment of patients with SOS.
Key words:
sinusoidal obstruction syndrome − monocrotaline − oxaliplatin − hepatotoxicity − experimental model
Zdroje
1. Helmy A. Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. Aliment Pharmacol Ther 2006;23:11−25.
2. Rubbia-Brandt L, Lauwers GY, Wang H, et al. Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin-associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis. Histopathology 2010;56:430−9.
3. Ito Y. A novel therapeutic strategy for liver sinusoidal obstruction syndrome. J Gastroenterol Hepatol 2009;24:933−4.
4. Rubbia-Brandt L. Sinusoidal obstruction syndrome. Clin Liver Dis 2010;14:651−68.
5. DeLeve LD, Ito Y, Bethea NW, et al. Embolization by sinusoidal lining cells obstructs the microcirculation in rat sinusoidal obstruction syndrome. Am J Physiol Gastrointest Liver Physiol 2003;284:G1045−52.
6. Conote R, Colet JM. A metabonomic evaluation of the monocrotaline-induced sinusoidal obstruction syndrome (SOS) in rats. Toxicol Appl Pharmacol 2014;276:147−56.
7. Nakamura K, Hatano E, Narita M, et al. Sorafenib attenuates monocrotaline-induced sinusoidal obstruction syndrome in rats through suppression of JNK and MMP-9. J Hepatol 2012;57:1037−57:
8. Joseph B, Kumaran V, Berishvili E, et al. Monocrotaline promotes transplanted cell engraftment and advances liver repopulation in rats via liver conditioning. Hepatology 2006;44:1411−20.
9. Wu YM, Joseph B, Berishvili E, et al. Hepatocyte transplantation and drug-induced perturbations in liver cell compartments. Hepatology 2008;47:279−87.
10. Schiffer E, Frossard JL, Rubbia-Brandt L, et al. Hepatic regeneration is decreased in a rat model of sinusoidal obstruction syndrome. J Surg Oncol 2009;99:439−46.
11. Alencar KN, Pereira L, da Silva E, et al. A novel adenosine A2a receptor agonist attenuates the progression of monocrotaline-induced pulmonary hypertension in rats. J Pulmon Resp Med 2013;S4:005.
12. Srinivasan P, Liu MY. Comparative potential therapeutic effect of sesame oil and peanut oil against acute monocrotaline (Crotalaria) poisoning in a rat model. J Vet Intern Med 2012;26:491−9.
13. Zopf DA, das Neves LA, Nikula KJ, et al. C - 122, a novel antagonist of serotonin receptor 5-HT 2B, prevents monocrotaline-induced pulmonary arterial hypertension in rats. Eur J Pharmacol 2011;670:195−203.
14. Chaumais MC, Ranchoux B, Montani D, et al. N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats. Respir Res 2014;15:65.
15. Zeng GQ, Liu R, Liao HX, et al. Single intraperitoneal injection of monocrotaline as a novel large animal model of chronic pulmonary hypertension in Tibet minipigs. PLoS One 2013;8:e78965.
16. DeLeve LD, McCuskey RS, Wang X, et al. Characterization of a reproducible rat model of hepatic veno-occlusive disease. Hepatology 1999;29:1779−29:
17. Carreras E. How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation. Br J Haematol 2015;168:481−91.
18. Masubuchi S, Komeda K, Takai S, et al. Chymase inhibition attenuates monocrotaline-induced sinusoidal obstruction syndrome in hamsters. Curr Med Chem 2013;20:2723−9.
19. Robinson SM, Mann J, Vasilaki A, et al. Pathogenesis of FOLFOX induced sinusoidal obstruction syndrome in a murine chemotherapy model. J Hepatol 2013;59:318−26.
20. Nakamura K, Hatano E, Miyagawa-Hayashino A, et al. Soluble thrombomodulin attenuates sinusoidal obstruction syndrome in rat through suppression of high mobility group box 1. Liver Int 2014;34:1473−87.
21. Okuno M, Hatano E, Nakamura K, et al. Regorafenib suppresses sinusoidal obstruction syndrome in rats. J Surg Res 2015;193:693−703.
Štítky
Anaesthesiology, Resuscitation and Inten Paediatric surgery Paediatric urologist Vascular surgery Chest surgery Maxillofacial surgery Plastic surgery Surgery Intensive Care Medicine Cardiac surgery Cardiology Neurosurgery Clinical oncology Orthopaedics Burns medicine Orthopaedic prosthetics Rehabilitation Nurse Traumatology Trauma surgery Urology Medical studentČlánok vyšiel v časopise
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