J Korean Surg Soc.  2013 Nov;85(5):219-224.

The effects of flavanoid on the treatment of hepatopulmonary syndrome

• Atalay T
• Cakir M
• Tekin A
• Kucukkartallar T
• Kargin S
• Kartal A
• Kaynak A

Abstract

PURPOSE
Hepatopulmonary syndrome is an arterial oxygenation disorder brought about by advanced liver failure and pulmonary vascular dilatations. The reason why hypoxia develops in hepatopulmonary syndrome depends on the broadening of perialveolar capillary veins. Our study aims to investigate the effects of Flavanoid on hepatopulmonary syndrome through its inhibition of nitric oxide.
METHODS
Three groups, each having 8 rats, were formed within the scope of our study. Group I (the control group) only received laparatomy, group II received choledoch ligation, and group III was administered Flavanoid (90% flavonoid diosmin, 10% flavonoid hesperidin) following choledoch ligation. The rats were administered Flavanoid at week two following choledoch ligation. The rats' livers and lungs were examined histopathologically following a five-week follow-up and the perialveolar vein diameters were measured. Arterial blood gases and biochemical parameters were evaluated.
RESULTS
It was seen that fibrosis and oxidative damage in the liver with obstructive jaundice as well as hypoxia with pulmonary perialveolar vein sizes were significantly lower than the other group with cirrhosis formed through the administration of Flavanoid.
CONCLUSION
We have concluded that Flavanoid administration might be useful in the treatment of hypoxia in hepatopulmonary syndrome and the delay of cirrhosis contraction.

Keyword

Hepatopulmonary syndrome; Flavanoid; Liver; Lung

MeSH Terms

Animals
Anoxia
Capillaries
Contracts
Dilatation
Diosmin
Fibrosis
Follow-Up Studies
Gases
Hepatopulmonary Syndrome*
Jaundice, Obstructive
Ligation
Liver
Liver Failure
Lung
Oxygen
Rats
Veins
Diosmin
Gases
Oxygen

Figure

• 

  Fig. 1 (A) Normal parenchymal liver tissue of the rats in control group. (B) Secondary biliary cirrhosis findings developed following choledoch ligation. (C) Wide biliary canaliculi, bridging necrosis at periportal distance and around vena centralis, fibrosis and mononuclear cell infiltration in liver parenchymal tissue of rats in group III. (D) Normal pulmonary tissue of rats in control group. (E) Increase in enlarged perialveolar vein diameter following choledoch ligation in rats of group II. (F) Pulmonary tissue of rats in group III. Increase in perialveolar vein diameter, perialveolar damage, neutrophile and mononuclear cell infiltration findings (H&E, ×100).

Reference

1. Flukiger M. Vorkommen von Trommelschlagel-formigen Fingerend-phalangen ohne chronische Veranderungen an der Lungen oder an Herzen. Wien Med Wochenschr. 1884; 34:1457.

2. Kennedy TC, Knudson RJ. Exercise-aggravated hypoxemia and orthodeoxia in cirrhosis. Chest. 1977; 72:305–309.

3. Krowka MJ, Cortese DA. Hepatopulmonary syndrome. Current concepts in diagnostic and therapeutic considerations. Chest. 1994; 105:1528–1537.

4. Ho V. Current concepts in the management of hepatopulmonary syndrome. Vasc Health Risk Manag. 2008; 4:1035–1041.

5. Fallon MB. Mechanisms of pulmonary vascular complications of liver disease: hepatopulmonary syndrome. J Clin Gastroenterol. 2005; 39:4 Suppl 2. S138–S142.

6. Chang SW, Ohara N. Pulmonary circulatory dysfunction in rats with biliary cirrhosis: an animal model of the hepatopulmonary syndrome. Am Rev Respir Dis. 1992; 145(4 Pt 1):798–805.

7. Tieppo J, Vercelino R, Dias AS, Silva Vaz MF, Silveira TR, Marroni CA, et al. Evaluation of the protective effects of quercetin in the hepatopulmonary syndrome. Food Chem Toxicol. 2007; 45:1140–1146.

8. Krowka MJ, Cortese DA. Severe hypoxemia associated with liver disease: Mayo Clinic experience and the experimental use of almitrine bismesylate. Mayo Clin Proc. 1987; 62:164–173.

9. Singh C, Sager JS. Pulmonary complications of cirrhosis. Med Clin North Am. 2009; 93:871–883.

10. Rodriguez-Roisin R, Krowka MJ, Herve P, Fallon MB. ERS Task Force Pulmonary-Hepatic Vascular Disorders (PHD) Scientific Committee. Pulmonary-hepatic vascular disorders (PHD). Eur Respir J. 2004; 24:861–880.

11. Lee KN, Yoon SK, Lee JW, Kim KN, Park BH, Kwak JY, et al. Hepatopulmonary syndrome induced by common bile duct ligation in a rabbit model: correlation between pulmonary vascular dilatation on thin-section CT and angiography and serum nitrite concentration or endothelial nitric oxide synthase (eNOS)1 expression. Korean J Radiol. 2004; 5:149–156.

12. Rolla G, Brussino L, Colagrande P, Scappaticci E, Morello M, Bergerone S, et al. Exhaled nitric oxide and impaired oxygenation in cirrhotic patients before and after liver transplantation. Ann Intern Med. 1998; 129:375–378.

13. Fallon MB, Abrams GA, Luo B, Hou Z, Dai J, Ku DD. The role of endothelial nitric oxide synthase in the pathogenesis of a rat model of hepatopulmonary syndrome. Gastroenterology. 1997; 113:606–614.

14. Zhang HY, Han de W, Su AR, Zhang LT, Zhao ZF, Ji JQ, et al. In testinal endotoxemia plays a central role in development of hepatopulmonary syndrome in a cirrhotic rat model induced by multiple pathogenic factors. World J Gastroenterol. 2007; 13:6385–6395.

15. Zhang HY, Han DW, Wang XG, Zhao YC, Zhou X, Zhao HZ. Experimental study on the role of endotoxin in the development of hepatopulmonary syndrome. World J Gastroenterol. 2005; 11:567–572.

16. Sztrymf B, Rabiller A, Nunes H, Savale L, Lebrec D, Le Pape A, et al. Prevention of hepatopulmonary syndrome and hyperdynamic state by pentoxifylline in cirrhotic rats. Eur Respir J. 2004; 23:752–758.

17. Kawada N, Seki S, Inoue M, Kuroki T. Effect of antioxidants, resveratrol, quercetin, and N-acetylcysteine, on the functions of cultured rat hepatic stellate cells and Kupffer cells. Hepatology. 1998; 27:1265–1274.

18. Santus R, Perdrix L, Haigle J, Morliere P, Maziere JC, Maziere C, et al. Daflon as a cellular antioxidant and a membrane-stabilizing agent in human fibroblasts irradiated by ultraviolet A radiation. Photodermatol Photoimmunol Photomed. 1991; 8:200–205.

19. Robak J, Gryglewski RJ. Flavonoids are scavengers of superoxide anions. Biochem Pharmacol. 1988; 37:837–841.