HISTOPATHOLOGICAL STUDY OF THE PROTECTIVE EFFECT OF SPIRULINA PLATENSIS ON FETAL LIVER OF MICE WITH ACUTE FATTY LIVER OF PREGNANCY
Objective: The protective effect of Spirulina platensis on the fetal liver of mice with acute fatty liver of pregnancy was investigated.
Methods: Small female mice were divided into four groups: A control group with a standard diet, a high-fat diet to induce liver steatosis, a high-fat diet plus Spirulina, and a high-fat diet plus Simvastatin given through gavage to protect the liver against steatosis. After 2 months, the female mice became pregnant by polygamy method at the same time they were treated by different diets. On day 17, the fetuses were removed by C-section, and histological studies were carried out on their livers.
Results: The results showed a significant decrease in liver steatosis in the group treated by Spirulina compared with the other groups (p<0.05). The fatty liver of pregnancy could lead to liver failure and death in both mother and fetus, and medications like Simvastatin that is used for the treatment of fatty liver are harmful to the fetus. However, Spirulina shows a positive effect on the treatment of both fetus and mother.
Conclusions: The results of this study show that Spirulina is an effective medical supplement in the treatment of fatty liver of pregnancy.
2. Sherlock S, Dooley J. The liver in pregnancy. In: Sherlock S, Dooley J, editors. Diseases of the Liver and Biliary System. London: Blackwell Science; 2002. p. 472-5.
3. Lee NM, Brady CW. Liver disease in pregnancy. World J Gastroenterol 2009;15:897.
4. Gargari SS. Acute fatty liver in pregnancy with complications of scites and bilateral pleural effusion in pregnant woman. Sci J Kurdistan Uni Medic Sci 2007;12:84-90.
5. Burroughs AK, Seong NG, Dojcinov DM, Scheuer PJ, Sherlock SV. Idiopathic acute fatty liver of pregnancy in 12 patients. QJM Int J Med 1982;51:481-97.
6. Chalifoux MR, Blank HL. Acute fatty liver of pregnancy and disseminated intravascular coagulation: A case report. J Obstet Anaesth Criti Care 2020;10:42.
7. Browning MF, Levy HL, Wilkins-Haug LE, Larson C, Shih VE. Fetal fatty acid oxidation defects and maternal liver disease in pregnancy. Obstet Gynecol 2006;107:115-20.
8. Treem W. Mitochondrial fatty acid oxidation and acute fatty liver of pregnancy. Semin Gastrointest Dis 2002;13:55-66.
9. Ibdah JA. Acute fatty liver of pregnancy: An update on pathogenesis and clinical implications. World J Gastroenterol 2006;12:7397.
10. Natarajan SK, Thangaraj KR, Eapen CE, Ramachandran A, Mukhopadhya A, Mathai M, et al. Liver injury in acute fatty liver of pregnancy: Possible link to placental mitochondrial dysfunction and oxidative stress. Hepatology 2010;51:191-200.
11. Mannaerts GP, Debeer LJ, Thomas J, De Schepper PJ. Mitochondrial and peroxisomal fatty acid oxidation in liver homogenates and isolated hepatocytes from control and clofibrate-treated rats. J Biol Chem 1979;254:4585-95.
12. Al-Ani OA. Drugs in pregnancy. Asian J Pharm Clin Res 2020;13:78-82.
13. Hoseini SM, Khosravi-Darani K, Mozafari MR. Nutritional and medical applications of spirulina microalgae. Mini Rev Med Chem 2013;13:1231-7.
14. Ku CS, Yang Y, Park Y, Lee J. Health benefits of blue-green algae: Prevention of cardiovascular disease and nonalcoholic fatty liver disease. J Med Food 2013;16:103-11.
15. Ramzi GA, Puneeth HR, Madhu CS, Sharada AC. Antagonistic effects of combination of flaxseed oil and spirulina platensis oil on their biological properties. Int J Pharm Pharm Sci 2015;7:122-7.
16. Serban MC, Sahebkar A, Dragan S, Stoichescu-Hogea G, Ursoniu S, Andrica F, et al. A systematic review and meta-analysis of the impact of spirulina supplementation on plasma lipid concentrations. Clin Nutr 2016;35:842-51.
17. Maniyar R, Umashankar GK. Effectiveness of spirulina mouthwash on reduction of dental plaque and gingivitis: A clinical study. Int J Pharm Pharm Sci 2017;9:136-9.
18. Ferreira-Hermosillo A, Torres-Duran PV, Juarez-Oandropeza MA. Hepatoprotective effects of spirulina maxima in patients with non-alcoholic fatty liver disease: A case series. J Med Case Rep 2010;4:103.
19. Deng R, Chow TJ. Hypolipidemic, antioxidant, and antiinflammatory activities of microalgae spirulina. Cardiovasc Ther 2010;28:e33-45.
20. Vedi M, Kalaiselvan S, Rasool M, Sabina EP. Protective effects of blue green algae spirulina Fusiformis against galactosamine-induced hepatotoxicity in mice. Asian J Pharm Clin Res 2013;6:150-4.
21. Coskun ZK, Kerem M, Gurbuz N, Omeroglu S, Pasaoglu H, Demirtas C, et al. The study of biochemical and histopathological effects of spirulina in rats with TNBS-induced colitis. Br Med J 2011;112:235-43.
22. Ismail MF, Ali DA, Fernando A, Abdraboh ME, Gaur RL, Ibrahim WM, et al. Chemoprevention of rat liver toxicity and carcinogenesis by spirulina. Int J Biol Sci 2009;5:377.
23. Khan M, Shobha JC, Mohan IK, Naidu MU, Sundaram C, Singh S, et al. Protective effect of spirulina against doxorubicin-induced cardiotoxicity. Phytother Res 2005;19:1030-7.
24. Karkos PD, Leong SC, Karkos CD, Sivaji N, Assimakopoulos DA. Spirulina in clinical practice: Evidence-based human applications. Evid Based Complement Altern Med 2011;2011:531053.
25. El-Baky HH, El Baz FK, El-Baroty GS. Enhancement of antioxidant production in spirulina Platensis under oxidative stress. Acta Physiol Plant 2009;31:623.
26. Kucera O, Cervinkova Z. Experimental models of non-alcoholic fatty liver disease in rats. World J Gastroenterol 2014;20:8364-76.
27. Fellmann L, Nascimento AR, Tibiriça E, Bousquet P. Murine models for pharmacological studies of the metabolic syndrome. Pharmacol Ther 2013;137:331-40.
28. Zou Y, Li J, Lu C, Wang J, Ge J, Huang Y, et al. High-fat emulsion-induced rat model of nonalcoholic steatohepatitis. Life Sci 2006;79:1100-7.
29. Blé-Castillo JL, Rodr?guez-Hernández A, Miranda-Zamora R, Juárez- Oropeza MA, D?az-Zagoya JC. Arthrospira maxima prevents the acute fatty liver induced by the administration of simvastatin, ethanol and a hypercholesterolemic diet to mice. Life Sci 2002;70:2665-73.
30. Wang JQ, Li J, Zou YH, Cheng WM, Lu C, Zhang L, et al. Preventive effects of total flavonoids of Litsea coreana leve on hepatic steatosis in rats fed with high fat diet. J Ethnopharmacol 2009;121:54-60.
31. Takahashi Y, Fukusato T. Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol 2014;20:15539.
32. Garber CC. Jendrassik-grof analysis for total and direct bilirubin in serum with a centrifugal analyzer. Clin Chem 1981;27:1410-6.
33. Seyido?lu N, Galip N. Effects of Saccharomyces cerevisiae and spirulina Platensis on growth performances and biochemical parameters in rabbits. Kafkas Univ Vet Fak Derg 2014;20:331-6.
34. Estrada JP, Bescós PB, Del Fresno AV. Antioxidant activity of different fractions of spirulina Platensis protean extract. Farmaco 2001;56:497-500.
35. Wu Q, Liu L, Miron A, Klímová B, Wan D, Ku?a K. The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina: An overview. Arch Toxicol 2016;90:1817-40.
36. Nagaoka S, Shimizu K, Kaneko H, Shibayama F, Morikawa K, Kanamaru Y, et al. A novel protein C-phycocyanin plays a crucial role in the hypocholesterolemic action of spirulina Platensis concentrate in rats. J Nutr 2005;135:2425-30.
37. Riss J, Décordé K, Sutra T, Delage M, Baccou JC, Jouy N, et al. Phycobiliprotein C-phycocyanin from spirulina Platensis is powerfully responsible for reducing oxidative stress and NADPH oxidase expression induced by an atherogenic diet in hamsters. J Agric Food Chem 2007;55:7962-7.
38. Finamore A, Palmery M, Bensehaila S, Peluso I. Antioxidant, immunomodulating, and microbial-modulating activities of the sustainable and ecofriendly spirulina. Oxid Med Cell Longev 2017;2017:3247528.
39. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44-84.
40. Desai K, Sivakami S. Spirulina: The wonder food of the 21st Century. Asia Pac Biotech News 2004;8:1298-302.
41. Brown SB, Houghton JD, Vernon DI. New trends in photobiology biosynthesis of phycobilins. Formation of the chromophore of phytochrome, phycocyanin and phycoerythrin. J Photochem Photobiol B 1990;5:3-23.
42. Martin A, Zulueta J, Hassoun P, Blumberg JB, Meydani M. Effect of Vitamin E on hydrogen peroxide production by human vascular endothelial cells after hypoxia/reoxygenation. Free Radic Biol Med 1996;20:99-105.
43. Ghaffarnejad M. Acute fatty liver of pregnancy and preeclampsia in a triplet gestation. Acta Med Iran 2007;45:161-4.
44. Pruis MG, Lendvai A, Bloks VW, Zwier MV, Baller JF, De Bruin A, et al. Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring. Acta Physiol 2014;210:215-27.
45. Zhan YT, An W. Roles of liver innate immune cells in nonalcoholic fatty liver disease. World J Gastroenterol 2010;16:4652.
46. Wieckowska A, Zein NN, Yerian LM, Lopez AR, McCullough AJ, Feldstein AE. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology 2006;44:27-33.
47. Feldstein AE, Canbay A, Guicciardi ME, Higuchi H, Bronk SF, Gores GJ. Diet associated hepatic steatosis sensitizes to fas mediated liver injury in mice. J Hepatol 2003;39:978-83.
48. Canbay A, Friedman S, Gores GJ. Apoptosis: The nexus of liver injury and fibrosis. Hepatology 2004;39:273-8.
49. Canbay A, Taimr P, Torok N, Higuchi H, Friedman S, Gores GJ. Apoptotic body engulfment by a human stellate cell line is profibrogenic. Lab Invest 2003;83:655.
50. Rius B, López-Vicario C, González-Périz A, Morán-Salvador E, García-Alonso V, Clària J, et al. Resolution of inflammation in obesity-induced liver disease. Front Immunol 2012;3:257.
51. McCurdy CE, Bishop JM, Williams SM, Grayson BE, Smith MS, Friedman JE, et al. Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates. J Clin Invest 2009;119:323-35.
52. Frazier TH, DiBaise JK, McClain CJ. Gut microbiota, intestinal permeability, obesity-induced inflammation, and liver injury. J PEN J Parenter Enteral Nutr 2011;35:14S-20.
53. Farrell GC, Teoh NC, McCuskey RS. Hepatic microcirculation in fatty liver disease. Anat Rec 2008;291:684-92.
54. McCuskey RS, Ito Y, Robertson GR, McCuskey MK, Perry M, Farrell GC. Hepatic microvascular dysfunction during evolution of dietary steatohepatitis in mice. Hepatology 2004;40:386-93.
55. Sato N, Eguchi H, Inoue A, Matsumura T, Kawano S, Kamada T. Hepatic microcirculation in Zucker fatty rats. In: Longmuir IS, editor. Oxygen Transport to Tissue VIII. Berlin, Germany: Springer; 1986. p. 477-83.
56. Hasegawa T, Ito Y, Wijeweera J, Liu J, Malle E, Farhood A, et al. Reduced inflammatory response and increased microcirculatory disturbances during hepatic ischemia-reperfusion injury in steatotic livers of ob/ob mice. Am J Physiol Gastrointest Liver Physiol 2007;292:G1385-95.
57. Teoh NC, Ito Y, Field J, Bethea NW, Amr D, McCuskey MK, et al. Diannexin, a novel annexin V homodimer, provides prolonged protection against hepatic ischemia-reperfusion injury in mice. Gastroenterology 2007;133:632-46.
58. McCuskey RS, Nishida J, Eguchi H, McDonnell D, Baker GL, Ekataksin W, et al. Role of endotoxin in the hepatic microvascular inflammatory response to ethanol. J Gastroenterol Hepatol 1995;10:S18-23.
59. Herrera E, Ortega-Senovilla H. Lipid metabolism during pregnancy and its implications for fetal growth. Curr pharm Biotechnol 2014;15:24-31.
60. Herrera E, Amusquivar E, Lopez-Soldado I, Ortega H. Maternal lipid metabolism and placental lipid transfer. Horm Res Paediatr 2006;65:59-64.
61. Haggarty P. Placental regulation of fatty acid delivery and its effect on fetal growth-a review. Placenta 2002;23:S28-38.
62. Leclercq IA. Pathogenesis of steatohepatitis: Insights from the study of animal models. Acta Gastroenterol Belg 2007;70:25-31.
63. Picardi A, D’Avola D, Gentilucci UV, Galati G, Fiori E, Spataro S, et al. Diabetes in chronic liver disease: From old concepts to new evidence. Diabetes Metab Res Rev 2006;22:274-83.
64. Schäffler A, Schölmerich J, Büchler C. Mechanisms of disease: Adipocytokines and visceral adipose tissue-emerging role in nonalcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol 2005;2:273.
65. Medina J, Fernández-Salazar LI, García-Buey L, Moreno-Otero R. Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis. Diabetes Care 2004;27:2057-66.
66. Aksoy L, Sözbilir NB. Effects of Matricaria chamomilla L. on lipid peroxidation, antioxidant enzyme systems, and key liver enzymes in CCl4-treated rats. Toxicol Environ Chem 2012;94:1780-8.
67. Balahoro?lu R, Dülger H, Hanefi Özbek H, Bayram ?, ?ekero?lu MR. Protective effects of antioxidants on the experimental liver and kidney toxicity in mice. Eur J Gen Med 2008;5:157-64.
68. Mahmoodzadeh Y, Mazani M, Rezagholizadeh L, Abbaspour A, Zabihi E, Pourmohammad P. Effect of Tanacetum parthenium extract on total antioxidant capacity of tissues damaged by carbon tetrachloride in rats. J Ardabil Univ Med Sci 2017;16:363-73.
69. Ariamanesh S, Faghihi M, Kadkhodaei M. The effect of reperfusion ischemia on level vitamin e in venous blood and kidney tissue in rat. Cell J (Yakhteh) 2001;3:39-44.
70. Kontush A, Finckh B, Karten B, Kohlschutter A, Beisiegel U. Antioxidant and prooxidant activity of alpha-tocopherol in human plasma and low density lipoprotein. J Lipid Res 1996;37:1436-48.
71. Yoshikawa T, Yasuda M, Ueda S, Naito Y, Tanigawa T, Oyamada H, et al. Vitamin E in gastric mucosal injury induced by ischemia-reperfusion. Am J Clin Nutr 1991;53:210S-4.
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