Morphological changes in rat liver during acute respiratory distress syndrome at different periods of experiment

Summary. Acute respiratory distress-syndrome (ARDS) is the leading cause of death of patients with COVID-19. Liver injury is a common complication during ARDS which can occur as a result of hypoxic changes caused by respiratory disorders, systemic inflammatory response syndrome, cytokine storm and disseminated intravascular coagulation syndrome (DIC) and is a manifestation of multiple organ failure which develops with this syndrome. The aim of the study – to assess the structural changes in rat liver at different stages of the experimental ARDS. Materials and Methods. For this study 48 mature white male rats were used. ARDS was modelled through intranasal administration of lipopolysaccharide (LPS) at a dose of 5 mg/kg. Tissues were harvested after 6h, 24h, 3 days, 7 days and 14 days. Histological studies were carried out according to generally accepted methods. Results. The tissues of control group did not contain any abnormalities. 6 hours after LPS there were dilated blood-filled vessels and inflammatory cell infiltration. 24 hours after LPS the perivascular leukocyte infiltration and the portal veins dilatation remained. There were dark hepatocytes with mitotic figures. On the 3rd day there were visible signs of thrombosis in the veins and sinusoids. The liver structure was damaged. It contained dark and light hepatocyte types. There were hepatocytes with the pyknotic nuclei. On the 7th day venous thrombi began dissolving. There were many pyknotic hepatocytic nuclei visible. On the 14th day the lobular liver structure remained damaged. There were separate groups of dark and light hepatocytes visible. Hepatocytes with the pyknotic nuclei remained. There were still signs of vascular haemostasis. Conclusions. It has been established that the ARDS modelled by us causes the pathological changes of liver structural components that correspond to the liver damage during COVID-19, hypoxic liver injury and DIC caused by the clinical ARDS

acute respiratory distress syndrome, liver injury, liver failure

https://doi.org/10.11603/bmbr.2706-6290.2022.4.13317

[1] Nardo AD, Schneeweiss-Gleixner M, Bakail M, Dixon ED, Lax SF, Trauner M. Pathophysiological mechanisms of liver injury in COVID-19. Liver International, 2021;41(1): 20-32. DOI: 10.1111/liv.14730.

[2] Shyamala, V, Harini, R, Manikandan D, Riyaz SM. Acute  Respiratory  Distress  Syndrome  (ARDS).  An Epidemiological Update on COVID-19, 2022;1.

[3] Huppert  LA,  Matthay  MA,  Ware  LB.  Pathogenesis of  acute  respiratory  distress  syndrome.  In:  Seminars  in respiratory  and  critical  care  medicine.  Thieme  Medical Publishers, 2019; 31-9. DOI: 10.1055/s-0039-1683996.

[4] Herrero R, Sánchez G, Asensio I, López E, Ferruelo A, Vaquero J, et al. Liver–lung interactions in acute respiratory distress  syndrome.  Intensive  Care  Med  Exp.  2020;8(1): 1-13. DOI: 10.1186/s40635-020-00337-9.

[5] Yang  P,  Formanek  P,  Scaglione  S,  Afshar  M. Risk  factors  and  outcomes  of  acute  respiratory  distress syndrome in critically ill patients with cirrhosis. Hepatol Res. 2019;49(3): 335-43. DOI: 10.1111/hepr.1324.

[6] Kozhemyakin  YuM,  Hromov  OS,  Filonenko  MA, Sajfetdinova GA. Scientific and practical recommendations for  keeping  laboratory  animals  and  working  with  them. [Науково-практичні  рекомендації  з  утримання  лабора-торних тварин та роботи з ними] Kyiv: Interservis; 2017. Ukrainian.

[7] Horalskyi  LP,  Khomych  VT,  &  Kononskyi  OI. Fundamentals    of    histological    technique    and morphofunctionalmethods  of  research  in  normal  and pathology.  [Основи  гістологічної  техніки  і  морфофункціональні методи досліджень у нормі та при патології]. Zhytomyr: Polissia; 2015. Ukrainian.

[8] Polinkevich S.G. Features of the liver ultrastructure at the young immature rats w ith chronic toxic hepatitis [Осо-бливості ультраструктури печінки молодих статевонезрілих щурів при хронічному токсичному гепатиті]. Bulletin of Morphology, 2014;20(2): 375-379. Ukrainian.

[9] Gando,  S.,  Fujishima,  S.,  Saitoh,  D.,  Shiraishi, A., Yamakawa,  K.,  Kushimoto,  S.,  &  Umemura,  Y.  The significance  of  disseminated  intravascular  coagulation  on multiple organ dysfunction during the early stage of acute respiratory  distress  syndrome.  Thrombosis  research, 2020;191: 15-21. DOI: 10.1016/j.thromres.2020.03.023.

[10] Livingstone SA, Wildi KS, Dalton HJ, Usman A, Ki KK, Passmore MR, Fraser JF. Coagulation dysfunction in acute respiratory  distress  syndrome  and  its  potential  impact  in inflammatory subphenotypes. Frontiers in Medicine. 2021;8: 723217. DOI: 10.3389/fmed.2021.723217.

[11] Chang,  J.  C. Acute  respiratory  distress  syndrome as  an  organ  phenotype  of  vascular  microthrombotic disease:  based  on  hemostatic  theory  and  endothelial molecular    pathogenesis.    Clinical    and    Applied Thrombosis/Hemostasis,  2019;25:  1076029619887437. DOI: 10.1177/1076029619887437.

[12] Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban  A,  et  al.  Epidemiology,  patterns  of  care,  and mortality  for  patients  with  acute  respiratory  distress syndrome  in  intensive  care  units  in  50  countries.  Jama, 2016;315(8): 788-800. DOI: 10.1001/jama.2016.0291.

[13] Dawood  RM,  Salum  GM, Abd  El-Meguid  M.  The impact  of  COVID-19  on  liver  injury:  COVID-19  and  liver injury. The American Journal of the Medical Sciences, 2021. DOI: 10.1016/j.amjms.2021.11.001.

[14] Harnisch LO, Baumann S, Mihaylov D, Kiehntopf M., Bauer, M., Moerer, O., Quintel, M. Biomarkers of cholestasis and liver injury in the early phase of acute respiratory distress syndrome and their pathophysiological value. Diagnostics, 2021;11(12): 2356. DOI: 10.3390/diagnostics11122356.

[15] Liu Q, Wang R, Qu G, Wang Y, Liu P, Zhu Y, Liu L. General  anatomy  report  of  novel  coronavirus  pneumonia patients. Journal of Forensic Medicine 2020;36: 21-3. DOI: 10.12116/j.issn.1004-5619.2020.01.005.

[16] Nardo AD, Schneeweiss-Gleixner M, Bakail M, Dixon ED, Lax SF, Trauner M. Pathophysiological mechanisms of liver injury in COVID-19. Liver International, 2021;41(1): 20-32. DOI: 10.1111/liv.14730.

[17] Zhang Y, Zheng L, Liu L, Zhao M, Xiao J, Zhao Q. Liver impairment in COVID-19 patients: a retrospective analysis of 115 cases from a single centre in Wuhan city, China. Liver Int. 2020;40(9): 2095-103. DOI: 10.1111/liv.14455.

[18] Licata A, Minissale MG, Distefano M, Montalto G. Liver injury, SARS-COV-2 infection and COVID-19: What physicians should really know? GastroHep, 2021;3(3): 121-30. DOI: 10.1002/ygh2.455.

[19] Herta T, Berg T. COVID-19 and the liver–Lessons learned. Liver International, 2021;41: 1-8. DOI: 10.1111/liv.14854.

[20] Sonzogni A, Previtali G, Seghezzi M, Grazia Alessio M, Gianatti  A,  Licini  L,  Nebuloni  M.  Liver  histopathology  in severe COVID 19 respiratory failure is suggestive of vascular alterations. Liver Int. 2020;40: 2110-6. DOI: 10.1111/liv.14601.