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Vol. 64 No. 13: Issue 13

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Preventive effect of Juniperus procera extract on liver injury induced by lithocholic acid

https://doi.org/10.14715/cmb/2018.64.13.12
Adel Qlayel Alkhedaide
Department of Medical Laboratories, Faculty of Applied Medical Sciences, Taif University, Turabah, Saudi Arabia

Corresponding Author(s) : Adel Qlayel Alkhedaide

adelglhk@hotmail.com

Cellular and Molecular Biology, Vol. 64 No. 13: Issue 13

Abstract

Bile acids are strong cytotoxic endogenous compounds implicated in several diseases in various organs, such as the liver, gallbladder and small and large intestines. Lithocholic acid is one such acid, produced by flora, and causes liver injury, cholestasis, and colon cancer. The present study aimed to examine the preventive effects of Juniperus procera extract on lithocholic acid"‘induced liver injury in experimental mice. Forty adult male mice were divided equally into four groups. The negative control group gained free access to food and water. The second group was orally treated with 150 mg/kg of Juniperus procera extract alone, the third group was treated with 1% lithocholic acid alone and the fourth group was co-treated with 150 mg/kg of Juniperus procera extract and 1% lithocholic acid. Blood and hepatic tissues were collected and assayed for biochemical, molecular and histopathological changes. Lithocholic acid toxicity shows a significant increase in the serum levels of the liver function parameters, which were prevented via the Juniperus procera co-administration. Furthermore, lithocholic acid significantly downregulates the mRNA expression of ABCG8, OATP2, SULT2A, CAR, FXR, CYP2B10, MRP2 and UGT1A, and Juniperus procera prevented this effect. Histopathological investigations of the hepatic tissues showed that lithocholic acid exhibited severe hepatotoxicity, with areas of irregularly distributed necrosis with inflammatory infiltration. Juniperus procera co-treated group showed a slight change in the hepatic tissue, diminished necrotic areas, and inflammatory infiltration. In conclusion, this study clarified the preventive effect of Juniperus procera extract administration on hepatotoxicity induced by lithocholic acid exposure in experimental mice.

Keywords

Lithocholic acid Juniperus procera Liver injury Bile acids Preventive effect.
Alkhedaide, A. Q. (2018). Preventive effect of Juniperus procera extract on liver injury induced by lithocholic acid. Cellular and Molecular Biology, 64(13), 63–68. https://doi.org/10.14715/cmb/2018.64.13.12
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References
  1. Fuchs M. Bile acid regulation of hepatic physiology: III. Regulation of bile acid synthesis: past progress and future challenges. American journal of physiology Gastrointestinal and liver physiology. 2003;284(4):G551-7. Epub 2003/03/13. doi: 10.1152/ajpgi.00468.2002. PubMed PMID: 12631556.
  2. Hofmann AF. Bile Acids: The Good, the Bad, and the Ugly. News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society. 1999;14:24-9. Epub 2001/06/08. PubMed PMID: 11390813.
  3. Hofmann AF, Hagey LR. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cellular and molecular life sciences : CMLS. 2008;65(16):2461-83. Epub 2008/05/20. doi: 10.1007/s00018-008-7568-6. PubMed PMID: 18488143.
  4. Stamp D. Antibiotic therapy may induce cancers in the colon and breasts through a mechanism involving bile acids and colonic bacteria. Medical hypotheses. 2004;63(3):555-6. Epub 2004/08/04. doi: 10.1016/j.mehy.2004.05.005. PubMed PMID: 15288388.
  5. Nancey S, Coffin B, Descos L, Flourie B. [Colonic microflora and cancer]. Gastroenterologie clinique et biologique. 2001;25(2 Pt 2):C79-84. Epub 2002/01/15. PubMed PMID: 11787385.
  6. Hofmann AF. The continuing importance of bile acids in liver and intestinal disease. Archives of internal medicine. 1999;159(22):2647-58. Epub 1999/12/22. PubMed PMID: 10597755.
  7. Hofmann AF. Detoxification of lithocholic acid, a toxic bile acid: relevance to drug hepatotoxicity. Drug Metab Rev. 2004;36(3-4):703-22. doi: 10.1081/DMR-200033475. PubMed PMID: 15554243.
  8. van Berge Henegouwen GP, Brandt KH, Eyssen H, Parmentier G. Sulphated and unsulphated bile acids in serum, bile, and urine of patients with cholestasis. Gut. 1976;17(11):861-9. PubMed PMID: PMC1411206.
  9. Holsti P. Cirrhosis of the Liver induced in Rabbits by Gastric Instillation of 3-Monohydroxycholanic Acid. Nature. 1960;186(4720):250-.
  10. Carey MC, Small DM. The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man. The Journal of clinical investigation. 1978;61(4):998-1026. Epub 1978/04/01. doi: 10.1172/jci109025. PubMed PMID: 659586; PubMed Central PMCID: PMCPMC372618.
  11. Zaki FG, Carey JB, Jr., Hoffbauer FW, Nwokolo C. Biliary reaction and choledocholithiasis induced in the rat by lithocholic acid. The Journal of laboratory and clinical medicine. 1967;69(5):737-48. Epub 1967/05/01. PubMed PMID: 6024553.
  12. Hofmann AF, Mysels KJ. Bile acid solubility and precipitation in vitro and in vivo: the role of conjugation, pH, and Ca2+ ions. Journal of lipid research. 1992;33(5):617-26. Epub 1992/05/01. PubMed PMID: 1619357.
  13. Adachi R, Honma Y, Masuno H, Kawana K, Shimomura I, Yamada S, et al. Selective activation of vitamin D receptor by lithocholic acid acetate, a bile acid derivative. Journal of lipid research. 2005;46(1):46-57. doi: 10.1194/jlr.M400294-JLR200.
  14. Bernstein H, Bernstein C, Payne CM, Dvorakova K, Garewal H. Bile acids as carcinogens in human gastrointestinal cancers. Mutation research. 2005;589(1):47-65. Epub 2005/01/18. doi: 10.1016/j.mrrev.2004.08.001. PubMed PMID: 15652226.
  15. Reddy BS. Diet and excretion of bile acids. Cancer research. 1981;41(9 Pt 2):3766-8. Epub 1981/09/01. PubMed PMID: 6266664.
  16. Cherbonnel-Lasserre C, Gauny S, Kronenberg A. Suppression of apoptosis by Bcl-2 or Bcl-xL promotes susceptibility to mutagenesis. Oncogene. 1996;13(7):1489-97. Epub 1996/10/03. PubMed PMID: 8875987.
  17. Dvorak K, Watts GS, Ramsey L, Holubec H, Payne CM, Bernstein C, et al. Expression of bile acid transporting proteins in Barrett's esophagus and esophageal adenocarcinoma. The American journal of gastroenterology. 2009;104(2):302-9. Epub 2009/01/29. doi: 10.1038/ajg.2008.85. PubMed PMID: 19174784; PubMed Central PMCID: PMCPMC4450811.
  18. Bernstein H, Bernstein C, Payne CM, Dvorak K. Bile acids as endogenous etiologic agents in gastrointestinal cancer. World journal of gastroenterology. 2009;15(27):3329-40. Epub 2009/07/18. PubMed PMID: 19610133; PubMed Central PMCID: PMCPMC2712893.
  19. Burits M, Asres K, Bucar F. The antioxidant activity of the essential oils of Artemisia afra, Artemisia abyssinica and Juniperus procera. Phytotherapy research : PTR. 2001;15(2):103-8. Epub 2001/03/27. PubMed PMID: 11268106.
  20. Loizzo MR, Tundis R, Conforti F, Saab AM, Statti GA, Menichini F. Comparative chemical composition, antioxidant and hypoglycaemic activities of Juniperus oxycedrus ssp. oxycedrus L. berry and wood oils from Lebanon. Food Chemistry. 2007;105(2):572-8.
  21. Ozturk M, Tumen I, Ugur A, Aydogmus-Ozturk F, Topcu G. Evaluation of fruit extracts of six Turkish Juniperus species for their antioxidant, anticholinesterase and antimicrobial activities. Journal of the science of food and agriculture. 2011;91(5):867-76. Epub 2011/03/09. doi: 10.1002/jsfa.4258. PubMed PMID: 21384354.
  22. El Beyrouthy M, Arnold N, Delelis-Dusollier A, Dupont F. Plants used as remedies antirheumatic and antineuralgic in the traditional medicine of Lebanon. Journal of ethnopharmacology. 2008;120(3):315-34. Epub 2008/09/24. doi: 10.1016/j.jep.2008.08.024. PubMed PMID: 18809483.
  23. Al-Attar AM, Alrobai AA, Almalki DA. Effect of Olea oleaster and Juniperus procera leaves extracts on thioacetamide induced hepatic cirrhosis in male albino mice. Saudi Journal of Biological Sciences. 2016;23(3):363-71. doi: 10.1016/j.sjbs.2015.08.011. PubMed PMID: PMC4818330.
  24. Alqasoumi SI, Abdel-Kader MS. Terpenoids from Juniperus procera with hepatoprotective activity. Pakistan journal of pharmaceutical sciences. 2012;25(2):315-22. Epub 2012/03/31. PubMed PMID: 22459455.
  25. Akeng'a TA, Chhabra SC. Analysis of the essential oil of Juniperus procera Endl. growing in Kenya. African journal of medicine and medical sciences. 1997;26(1-2):79-81. Epub 1997/03/01. PubMed PMID: 10895238.
  26. Woolbright BL, Jaeschke H. Therapeutic targets for cholestatic liver injury. Expert opinion on therapeutic targets. 2016;20(4):463-75. Epub 2015/10/20. doi: 10.1517/14728222.2016.1103735. PubMed PMID: 26479335; PubMed Central PMCID: PMCPMC4890577.
  27. Festi D, Morselli Labate AM, Roda A, Bazzoli F, Frabboni R, Rucci P, et al. Diagnostic effectiveness of serum bile acids in liver diseases as evaluated by multivariate statistical methods. Hepatology (Baltimore, Md). 1983;3(5):707-13. Epub 1983/09/01. PubMed PMID: 6618438.
  28. Chai J, Feng X, Zhang L, Chen S, Cheng Y, He X, et al. Hepatic Expression of Detoxification Enzymes Is Decreased in Human Obstructive Cholestasis Due to Gallstone Biliary Obstruction. PLoS ONE. 2015;10(3):e0120055. doi: 10.1371/journal.pone.0120055. PubMed PMID: PMC4370735.
  29. Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiological reviews. 2003;83(2):633-71. Epub 2003/03/29. doi: 10.1152/physrev.00027.2002. PubMed PMID: 12663868.
  30. Donner MG, Schumacher S, Warskulat U, Heinemann J, Häussinger D. Obstructive cholestasis induces TNF-α- and IL-1β-mediated periportal downregulation of Bsep and zonal regulation of Ntcp, Oatp1a4, and Oatp1b2. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2007;293(6):G1134-G46. doi: 10.1152/ajpgi.00079.2007.
  31. Ilyas G, Zhao E, Liu K, Lin Y, Tesfa L, Tanaka KE, et al. Macrophage autophagy limits acute toxic liver injury in mice through down regulation of interleukin-1β. Journal of hepatology. 2016;64(1):118-27. doi: 10.1016/j.jhep.2015.08.019. PubMed PMID: PMC4691423.
  32. Su H, Ma C, Liu J, Li N, Gao M, Huang A, et al. Downregulation of nuclear receptor FXR is associated with multiple malignant clinicopathological characteristics in human hepatocellular carcinoma. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2012;303(11):G1245-G53. doi: 10.1152/ajpgi.00439.2011. PubMed PMID: PMC3532459.
  33. Tryndyak V, de Conti A, Kobets T, Kutanzi K, Koturbash I, Han T, et al. Interstrain differences in the severity of liver injury induced by a choline- and folate-deficient diet in mice are associated with dysregulation of genes involved in lipid metabolism. The FASEB Journal. 2012;26(11):4592-602. doi: 10.1096/fj.12-209569. PubMed PMID: PMC3475259.
  34. Elferink MG, Olinga P, Draaisma AL, Merema MT, Faber KN, Slooff MJ, et al. LPS-induced downregulation of MRP2 and BSEP in human liver is due to a posttranscriptional process. American journal of physiology Gastrointestinal and liver physiology. 2004;287(5):G1008-16. Epub 2004/06/19. doi: 10.1152/ajpgi.00071.2004. PubMed PMID: 15205115.
  35. Kim J-H, Nam WS, Kim SJ, Kwon OK, Seung EJ, Jo JJ, et al. Mechanism Investigation of Rifampicin-Induced Liver Injury Using Comparative Toxicoproteomics in Mice. International Journal of Molecular Sciences. 2017;18(7):1417. doi: 10.3390/ijms18071417. PubMed PMID: PMC5535909.
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