Zhang J, Fallon MB. Hepatopulmonary syndrome: update on pathogenesis and clinical features. Nat Rev Gastroenterol Hepatol. 2012;9:539–49.

Article  PubMed  CAS  Google Scholar 

Soulaidopoulos S, Cholongitas E, Giannakoulas G, Vlachou M, Goulis I. Update on current and emergent data on hepatopulmonary syndromeWorld. J Gastroenterol. 2018;24(12):1285–98.

CAS  Google Scholar 

Grilo-Bensusan I, Pascasio-Acevedo J. Hepatopulmonary syndrome: what we know and what we would like to know. World J Gastroenterol. 2016;22(25):5728–41.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Gómez F, Barberà J, Roca J, Burgos F, Gistau C, Rodríguez-Roisin R. Effects of nebulized N(G)-nitro-L-arginine methyl ester in patients with hepatopulmonary syndrome. Hepatol. 2006;43(5):1084–91.

Article  Google Scholar 

Ling Y, Zhang J, Luo B, Song D, Liu L, Tang L, et al. The role of endothelin-1 and the endothelin B receptor in the pathogenesis of hepatopulmonary syndrome in the rat. Hepatol. 2004;39:1593–602.

Article  CAS  Google Scholar 

Raevens S, Fallon M. Potential clinical targets in hepatopulmonary syndrome: lessons from experimental models. Hepatol. 2018;68(5):2016–28.

Article  Google Scholar 

Tieppo J, Cuevas MJ, Vercelino R, Tuñón MJ, Marroni NP, González-Gallego J. Quercetin administration ameliorates pulmonary complications of cirrhosis in rats. J Nutr. 2009;139(7):1339–46.

Article  PubMed  CAS  Google Scholar 

Gu HJ, Zuo S, Liu HY, Gu LL, Yang XW, Liao J, et al. CX3CR1 participates in pulmonary angiogenesis in experimental hepatopulmonary syndrome mice through inhibiting AKT/ERK signaling pathway and regulating NO/NOS release. Eur Rev Med Pharmacol Sci. 2019;23(15):6645–56.

PubMed  Google Scholar 

Yang W, Hu B, Wu W, Batra S, Blackburn M, Alcorn J, et al. Alveolar type II epithelial cell dysfunction in rat experimental Hepatopulmonary syndrome (HPS). PLoS One. 2014;9(11):e113451.

Article  PubMed  PubMed Central  Google Scholar 

Han MK, Barreto TA, Martinez FJ, Comstock AT, Sajjan US. Randomised clinical trial to determine the safety of quercetin supplementation in patients with chronic obstructive pulmonary disease. BMJ Open Respir Res. 2020;7:e000392.

Article  PubMed  PubMed Central  Google Scholar 

Lu J, Wang Z, Li S, Xin Q, Yuan M, Li H, et al. Quercetin inhibits the migration and invasion of HCCLM3 cells by suppressing the expression of p-Akt1, matrix metalloproteinase (MMP) MMP-2, and MMP-9. Med Sci Monit. 2018;24:2583–9.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Li X, Chen Y, Wang L, Shang G, Zhang C, Zhao Z, et al. Quercetin alleviates pulmonary angiogenesis in a rat model of hepatopulmonary syndrome. Braz J Med Biol Res. 2016;49(7):e5326.

Article  PubMed  PubMed Central  Google Scholar 

Li X, Jin Q, Yao Q, Xu B, Li L, Zhang S, et al. The flavonoid quercetin ameliorates liver inflammation and fibrosis by regulating hepatic macrophages activation and polarization in mice. Front Pharmacol. 2018;9(9):72.

Article  PubMed  PubMed Central  Google Scholar 

Araújo NPDS, de Matos NA, Oliveira M, de Souza ABF, Castro TF, Machado-Júnior PA, et al. Quercetin improves pulmonary function and prevents emphysema caused by exposure to cigarette smoke in male mice. Antioxidants (Basel). 2022;11(2):181.

Article  PubMed  Google Scholar 

National Institutes of Health (U.S). Institutional Animal Care and Use cmmittee guidebook. second edition. published by, Office of Laboratory Animal Welfare, National Institutes of Health; 2002.

Declaration of Helsinki 1964. Recommendations guiding physicians in biomedical research involving human subjects. BMJ. 1996;313:1448.

Abushady EA, Elagaty SM, Nassef NA, Abdelhamid GS. The potential hepatoprotective effect of quercetin on cholestatic liver injury in rats. Bull Egypt Soc Physiol Sci. 2019;40(1):84–95.

Tag CG, Sauer-Lehnen S, Weiskirchen S, Borkham-Kamphorst E, Tolba RH, Tacke F, and Weiskirchen F. Bile duct ligation in mice: induction of inflammatory liver injury and fibrosis by obstructive cholestasis. J Vis Exp. 2015;10(96).

Zhao Y, Zhang M, Xiong RP, Chen XY, Li P, Ning YL, et al. Somatostatin reduces the acute lung injury of mice via increasing the affinity of glucocorticoid receptor. Cell Physiol Biochem. 2016;38(4):1354–64.

Article  PubMed  CAS  Google Scholar 

Balyakina EV, Chen D, Lawrence ML, Manning S, Parker RE, Shappell SB, et al. ET-1 receptor gene expression and distribution in L1 and L2 cells from hypertensive sheep pulmonary artery. Am J Physiol Lung Cell Mol Physiol. 2002;283(1):L42–51.

Article  PubMed  CAS  Google Scholar 

Black JG, Black LJ. Microbiology: principles and explorations: John Wiley & Sons; 2018.

Google Scholar 

Widbiller M, Rothmaier C, Saliter D, Wölflick M, Rosendahl A, Buchalla W, et al. Histology of human teeth: standard and specific staining methods revisited. Arch Oral Biol. 2021;127:105136.

Article  PubMed  CAS  Google Scholar 

Lu JW, Yang WY, Lin YM, Jin SL, Yuh CH. Hepatitis B virus X antigen and aflatoxin B1 synergistically cause hepatitis, steatosis and liver hyperplasia in transgenic zebrafish. Acta Histochem. 2013;115(7):728–39.

Article  PubMed  CAS  Google Scholar 

Drury R, Carleton WE. Histological techniques. 5th ed. New York and Toronto: Oxford University Press. London; 1980.

Google Scholar 

Bancroft JD, Gamble M. Theory and Practice. In: Histological Techniques. 5th ed. London: Churchill Livingstone; 2002.

Google Scholar 

Sridharan G, Shankar AA. Toluidine blue: a review of its chemistry and clinical utility. J Oral Maxillofac Pathol. 2012;16(2):251–5.

Article  PubMed  PubMed Central  Google Scholar 

Suvarna K, Layton C, Bancroft J. Theory and practice of histological techniques, vol. 203. 7th ed. Churchill Livingstone, USA; 2013. p. 500.

Weidenheim KM, Hinchey WW, Campbell WG Jr. Hyperinsulinemic hypoglycemia in adults with islet-cell hyperplasia and degranulation of exocrine cells of the pancreas. Am J Clin Pathol. 1983;79:14–24.

Article  PubMed  CAS  Google Scholar 

Marković Filipović J, Miler M, Kojić D, Karan J, Ivelja I, Čukuranović Kokoris J, Matavulj M. Effect of acrylamide treatment on Cyp2e1 expression and redox status in rat hepatocytes. Int J Mol Sci. 2022;23(11):6062.

Silva AI, Gvazava N, Bölükbas D, Stenlo M, Dong J, Pierre L, et al. A semi-quantitative scoring system for green histopathological evaluation of large animal models of acute lung injury. Bio-protocol. 2022;12(16).

Sawilowsky S. Misconceptions leading to choosing the t test over the Wilcoxon Mann-Whitney U test for shift in location parameter. J Mod Appl Stat Methods. 2005;4(2):598–600.

Article  Google Scholar 

Bosco AD, Schedler FB, Colares JR, Schemitt EG, Hartmann RM, Forgiarini Junior LA, Dias AS and Marroni NP. Melatonin effects on pulmonary tissue in the experimental model of Hepatopulmonary syndrome. J Bras Pneumol. 2019;45(3):e20170164. https://doi.org/10.1590/1806-3713/e20170164.

Kowalczyk A, Kleniewska P, Kolodziejczyk M, Skibska B, Goraca A. The role of endothelin-1 and endothelin receptor antagonists in inflammatory response and sepsis. Arch Immunol Ther Exp. 2015;63(1):41–52. https://doi.org/10.1007/s00005-014-0310-1.

Wu MH, Huang CY, Lin JA, Wang SW, Peng CY, Cheng HC, et al. Endothelin-1 promotes vascular endothelial growth factor-dependent angiogenesis in human chondrosarcoma cells. Oncogene. 2014;33(13):1725–35.

Article  PubMed  CAS  Google Scholar 

Zhang HY, Han DW, Su AR, Zhang LT, Zhao ZF, Ji JQ, et al. Intestinal endotoxemia plays a central role in development of hepatopulmonary syndrome in a cirrhotic rat model induced by multiple pathogenic factors. World J Gastroenterol. 2007;13:6385–95.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Luo B, Tang L, Wang Z, Zhang J, Ling Y, Feng W, Sun J, Stockard C, Frost A, Chen Y. Cholangiocyte Endothelin 1 and Transforming Growth Factor β1 Production in Rat Experimental Hepatopulmonary Syndrome. Gastroenterology. 2005;129(2):682–95.

Nayyar D, Man HS, Granton J, Lilly LB, Gupta S. Proposed management algorithm for severe hypoxemia after liver transplantation in the hepatopulmonary syndrome. Am J Transplant. 2015;15:903–13.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Tang L, Luo B, Patel RP, Ling Y, Zhang J, Fallon MB. Modulation of pulmonary endothelial endothelin B receptor expression and signaling: implications for experimental hepatopulmonary syndrome. Am J Physiol Lung Cell Mol Physiol. 2007;292:L1467–72.

Article  PubMed  CAS  Google Scholar 

Zopey R, Susanto I, Barjaktarevic I, Wang T. Transition from hepatopulmonary , syndrome to portopulmonary hypertension: A case series of 3 patients. Case Rep Pulmonol. 2013;561870.

Cosarderelioglu C, Cosar AM, Gurakar M, Dagher NN, Gurakar A. Hepatopulmonary syndrome and liver transplantation: a recent review of the literature. J Clin Transl Hepatol. 2016;4(1):47–53.

Article  PubMed  PubMed Central  Google Scholar 

Shikata F, Sakaue T, Nakashiro K-i, Okazaki M, Kurata M, Okamura T, Okura M, Ryugo M,  Nakamura Y, Yasugi T, Higashiyama S,Izutani H. Pathophysiology of lung injury induced by common bile duct ligation in mice. PLoS One. 2014;9(4):e94550.

Zhang J, Ling Y, Tang L, Luo B, Pollock DM, Fallon MB. Attenuation of experimental hepatopulmonary syndrome in endothelin B receptor-deficient rats. Am J Physiol Gastrointest liver Physiol. 2009b;296(4):G704–8.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Thenappan T, Goel A, Marsboom G, Fang YH, Toth PT, Zhang HJ, et al. A central role for CD68+ macrophages in hepatopulmonary syndrome. Reversal by macrophage depletion. Am J Respir Crit Care Med. 2011;183:1080–91.

Article  PubMed  Google Scholar 

DeMartino ES, Krowka MJ. Pulmonary vascular complications of liver disease. Int Anesthesiol Clin. 2017;55(2):67–80.

Article  PubMed  Google Scholar 

Melo-Silva CA, Gaio E, Trevizoli JE, Souza CS, Goncalves AS, Sousa GC, et al. Respiratory mechanics and lung tissue remodeling in a hepatopulmonary syndrome rat model. Respir Physiol Neurobiol. 2011;179(2–3):326–33.

Article  PubMed  Google Scholar 

Horvatits T, Drolz A, Rutter K, Roedl K, Fauler G, Muller C, et al. Serum bile acids in patients with hepatopulmonary syndrome. Z Gastroenterol. 2017;55(4):361–7.

PubMed  CAS  Google Scholar 

Kumar V, Abbas AK, Aster JC. Robbins basic pathology e-book: Elsevier Health Sciences; 2017.

Google Scholar 

Comellas AP, Briva A, Dada LA, Butti ML, Trejo HE, Yshii C, et al. Endothelin-1 impairs alveolar epithelial function via endothelial ETB receptor. Am J Respir Crit Care Med. 2009;179(2):113–22.

Article  PubMed  CAS