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Volume 1, Issue 1
  • ISSN: 2666-2906
  • E-ISSN: 2666-2914

Abstract

Background

Bile acids (BAs) are the major lipid components of bile. They are synthesized from cholesterol in the liver and stored in the gallbladder. BAs have gained attention as drug candidates to control obesity and/or diabetic condition due to their role in lipid and glucose metabolism.

Objective

This study aimed to evaluate the antisteatotic and antioxidant potential of deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), two BAs with opposite physico-chemical features.

Methods

Different concentrations of DCA and UDCA in the micromolar range were tested on cultured hepatoma cells after loading with an excess of fatty acids to mimic non-alcoholic fatty liver disease (NAFLD) . Experimental analyses included cell viability, lipid accumulation and lipid peroxidation in steatotic hepatocytes before and after exposure to either DCA or UDCA.

Results

Both UDCA and DCA improved lipid dysmetabolism and oxidative stress conditions in the steatotic hepatocytes. However, while UDCA was more effective as lipid lowering agent, DCA showed a greater antioxidant effect.

Conclusion

UDCA seems to have better protective and beneficial potential than DCA, as it is able to both alleviate lipid accumulation in the steatotic liver cells, but also to play antioxidant effect.

© 2022 Bentham Science Publishers
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2022-04-01
2025-02-17

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References

  1. Di CiaulaA. GarrutiG. Lunardi BaccettoR. Molina-MolinaE. BonfrateL. WangD. Q. Portincasa, p. bile acid physiology.Ann. Hepato201716Suppl. 1: s3-105s4-s1410.5604/01.3001.0010.5493
     [Google Scholar]
  2. Di CiaulaA. WangD. Q. Molina-MolinaE. Lunardi BaccettoR. CalamitaG. PalmieriV. O. Portincasa, p. bile acids and cancer: direct and environmental-dependent effects.Ann. hepatol.201716Suppl. 1: s3-105s87-s105
     [Google Scholar]
  3. GarrutiG. Di CiaulaA. WangH. H. WangD. Q. Portincasa, p. cross-talk between bile acids and gastro-intestinal and thermogenic hormones: clues from bariatric surgery.Annals of hepato.201716Suppl. 1: s3-105s68-s82
     [Google Scholar]
  4. AhmadT.R. HaeuslerR.A. Bile acids in glucose metabolism and insulin signalling - mechanisms and research needs.Nat. Rev. Endocrinol.2019151270171210.1038/s41574‑019‑0266‑731616073
     [Google Scholar]
  5. PerezM.J. BrizO. Bile-acid-induced cell injury and protection.World J. Gastroenterol.200915141677168910.3748/wjg.15.167719360911
     [Google Scholar]
  6. CaoH. XuM. DongW. DengB. WangS. ZhangY. WangS. LuoS. WangW. QiY. GaoJ. CaoX. YanF. WangB. Secondary bile acid-induced dysbiosis promotes intestinal carcinogenesis.Int. J. Cancer2017140112545255610.1002/ijc.3064328187526
     [Google Scholar]
  7. OthmanM.O. DunkelbergJ. RoyP.K. Urosdeoxycholic acid in primary sclerosing cholangitis: a meta-analysis and systematic review.Arab J. Gastroenterol.201213310311010.1016/j.ajg.2012.06.01123122450
     [Google Scholar]
  8. AscherB. FellmannJ. MonheitG. ATX-101 (deoxycholic acid injection) for reduction of submental fat.Expert Rev. Clin. Pharmacol.2016991131114310.1080/17512433.2016.121591127457304
     [Google Scholar]
  9. PortincasaP. WangD.Q.H. Gallstones. In: Yamada's Atlas of Gastroenterology, 5th ed.; Podolsky, K. D.; Camilleri, M.; Fitz, J. G.; Kalloo, A. N.; Shanahan, F.; Wang, T. C. Wiley-Blackwell: Hoboken, New Jersey (USA),2016pp. 335-353
     [Google Scholar]
  10. PouponR. Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: an overview of their mechanisms of action.Clin. Res. Hepatol. Gastroenterol.201236Suppl. 1S3S1210.1016/S2210‑7401(12)70015‑323141891
     [Google Scholar]
  11. MahmoudA.A. ElshazlyS.M. Ursodeoxycholic acid ameliorates fructose-induced metabolic syndrome in rats.PLoS One201499e10699310.1371/journal.pone.010699325202970
     [Google Scholar]
  12. OhA.R. BaeJ.S. LeeJ. ShinE. OhB.C. ParkS.C. ChaJ.Y. Ursodeoxycholic acid decreases age-related adiposity and inflammation in mice.BMB Rep.201649210511010.5483/BMBRep.2016.49.2.17326350747
     [Google Scholar]
  13. QuinteroP. PizarroM. SolísN. ArabJ.P. PadillaO. RiquelmeA. ArreseM. Bile acid supplementation improves established liver steatosis in obese mice independently of glucagon-like peptide-1 secretion.J. Physiol. Biochem.201470366767410.1007/s13105‑014‑0336‑124816727
     [Google Scholar]
  14. MuellerM. ThorellA. ClaudelT. JhaP. KoefelerH. LacknerC. HoeselB. FaulerG. StojakovicT. EinarssonC. MarschallH.U. TraunerM. Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity.J. Hepatol.20156261398140410.1016/j.jhep.2014.12.03425617503
     [Google Scholar]
  15. BaldiniF. BartolozziA. ArditoM. VociA. PortincasaP. VassalliM. VerganiL. Biomechanics of cultured hepatic cells during different steatogenic hits.J. Mech. Behav. Biomed. Mater.20199729630510.1016/j.jmbbm.2019.05.03631151002
     [Google Scholar]
  16. EckelR.H. AlbertiK.G. GrundyS.M. ZimmetP.Z. The metabolic syndrome.Lancet2010375971018118310.1016/S0140‑6736(09)61794‑320109902
     [Google Scholar]
  17. VecchioneG. GrasselliE. CioffiF. BaldiniF. OliveiraP.J. SardãoV.A. CorteseK. LanniA. VociA. PortincasaP. VerganiL. The nutraceutic silybin counteracts excess lipid accumulation and ongoing oxidative stress in an in vitro model of non-alcoholic fatty liver disease progression.Front. Nutr.201744210.3389/fnut.2017.0004228971098
     [Google Scholar]
  18. Molina-MolinaE. Lunardi BaccettoR. WangD.Q. de BariO. KrawczykM. PortincasaP. Exercising the hepatobiliary-gut axis. The impact of physical activity performance.Eur. J. Clin. Invest.2018488e1295810.1111/eci.1295829797516
     [Google Scholar]
  19. DufourJ.F. CaussyC. LoombaR. Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges.Gut202069101877188410.1136/gutjnl‑2019‑31910432381514
     [Google Scholar]
  20. GrasselliE. BaldiniF. VecchioneG. OliveiraP.J. SardãoV.A. VociA. PortincasaP. VerganiL. Excess fructose and fatty acids trigger a model of non alcoholic fatty liver disease progression in vitro: Protective effect of the flavonoid silybin.Int. J. Mol. Med.201944270571210.3892/ijmm.2019.423431173180
     [Google Scholar]
  21. ClaytonD.F. WeissM. DarnellJ.E. Jr Liver-specific RNA metabolism in hepatoma cells: variations in transcription rates and mRNA levels.Mol. Cell. Biol.19855102633264110.1128/MCB.5.10.26333841793
     [Google Scholar]
  22. Joshi-BarveS. BarveS.S. AmancherlaK. GobejishviliL. HillD. CaveM. HoteP. McClainC.J. Palmitic acid induces production of proinflammatory cytokine interleukin-8 from hepatocytes.Hepatology200746382383010.1002/hep.2175217680645
     [Google Scholar]
  23. GrasselliE. CanesiL. PortincasaP. VociA. VerganiL. DemoriI. Models of non-alcoholic fatty liver disease and potential translational value: the effects of 3,5-L-diiodothyronine.Ann. Hepatol.201716570771910.5604/01.3001.0010.271328809727
     [Google Scholar]
  24. BradfordM.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal. Biochem.19767224825410.1016/0003‑2697(76)90527‑3942051
     [Google Scholar]
  25. VerganiL. VecchioneG. BaldiniF. GrasselliE. VociA. PortincasaP. FerrariP.F. AliakbarianB. CasazzaA.A. PeregoP. Polyphenolic extract attenuates fatty acid-induced steatosis and oxidative stress in hepatic and endothelial cells.Eur. J. Nutr.20185751793180510.1007/s00394‑017‑1464‑528526925
     [Google Scholar]
  26. GrasselliE. VociA. CanesiL. De MatteisR. GogliaF. CioffiF. FugassaE. GalloG. VerganiL. Direct effects of iodothyronines on excess fat storage in rat hepatocytes.J. Hepatol.20115461230123610.1016/j.jhep.2010.09.02721145833
     [Google Scholar]
  27. IguchiH. KojoS. IkedaM. Lipid peroxidation and disintegration of the cell membrane structure in cultures of rat lung fibroblasts treated with asbestos.J. Appl. Toxicol.199313426927510.1002/jat.25501304098376727
     [Google Scholar]
  28. BomzonA. LjubuncicP. Ursodeoxycholic acid and in vitro vasoactivity of hydrophobic bile acids.Dig. Dis. Sci.20014692017202410.1023/A:101066390482011575458
     [Google Scholar]
  29. LjubuncicP. FuhrmanB. OiknineJ. AviramM. BomzonA. Effect of deoxycholic acid and ursodeoxycholic acid on lipid peroxidation in cultured macrophages.Gut199639347547810.1136/gut.39.3.4758949657
     [Google Scholar]
  30. ImE. MartinezJ.D. Ursodeoxycholic acid (UDCA) can inhibit deoxycholic acid (DCA)-induced apoptosis via modulation of EGFR/Raf-1/ERK signaling in human colon cancer cells.J. Nutr.2004134248348610.1093/jn/134.2.48314747693
     [Google Scholar]
  31. MoustafaT. FickertP. MagnesC. GuellyC. ThueringerA. FrankS. KratkyD. SattlerW. ReicherH. SinnerF. GumholdJ. SilbertD. FaulerG. HöflerG. LassA. ZechnerR. TraunerM. Alterations in lipid metabolism mediate inflammation, fibrosis, and proliferation in a mouse model of chronic cholestatic liver injury.Gastroenterology20121421140151.e1210.1053/j.gastro.2011.09.05122001865
     [Google Scholar]
  32. Di CiaulaA. WangD.Q. PortincasaP. An update on the pathogenesis of cholesterol gallstone disease.Curr. Opin. Gastroenterol.2018342718010.1097/MOG.000000000000042329283909
     [Google Scholar]
  33. PouponR.E. LindorK.D. Cauch-DudekK. DicksonE.R. PouponR. HeathcoteE.J. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis.Gastroenterology1997113388489010.1016/S0016‑5085(97)70183‑59287980
     [Google Scholar]
  34. BacqY. SentilhesL. ReyesH.B. GlantzA. KondrackieneJ. BinderT. NicastriP.L. LocatelliA. FloreaniA. HernandezI. Di MartinoV. Efficacy of ursodeoxycholic acid in treating intrahepatic cholestasis of pregnancy: a meta-analysis.Gastroenterology201214361492150110.1053/j.gastro.2012.08.00422892336
     [Google Scholar]
  35. GoossensJ.F. BaillyC. Ursodeoxycholic acid and cancer: From chemoprevention to chemotherapy.Pharmacol. Ther.201920310739610.1016/j.pharmthera.2019.10739631356908
     [Google Scholar]
  36. GheibiS. Gouvarchin GhalehH.E. MotlaghB.M. AzarbayjaniA.F. ZareiL. Therapeutic effects of curcumin and ursodexycholic acid on non-alcoholic fatty liver disease.Biomed. Pharmacother.201911510893810.1016/j.biopha.2019.10893831071511
     [Google Scholar]
  37. LindorK.D. KowdleyK.V. HeathcoteE.J. HarrisonM.E. JorgensenR. AnguloP. LympJ.F. BurgartL. ColinP. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial.Hepatology200439377077810.1002/hep.2009214999696
     [Google Scholar]
  38. ChiangJ.Y.L. FerrellJ.M. Bile Acid metabolism in liver pathobiology.Gene Expr.2018182718710.3727/105221618X1515601838551529325602
     [Google Scholar]
  39. Martinez-DiezM.C. SerranoM.A. MonteM.J. MarinJ.J. Comparison of the effects of bile acids on cell viability and DNA synthesis by rat hepatocytes in primary culture.Biochim. Biophys. Acta20001500215316010.1016/S0925‑4439(99)00099‑X10657584
     [Google Scholar]
  40. ZouB. YeoY.H. NguyenV.H. CheungR. IngelssonE. NguyenM.H. Prevalence, characteristics and mortality outcomes of obese, nonobese and lean NAFLD in the United States, 1999-2016.J. Intern. Med.2020288113915110.1111/joim.1306932319718
     [Google Scholar]
  41. AngelinB. HershonK.S. BrunzellJ.D. Bile acid metabolism in hereditary forms of hypertriglyceridemia: evidence for an increased synthesis rate in monogenic familial hypertriglyceridemia.Proc. Natl. Acad. Sci. USA198784155434543810.1073/pnas.84.15.54343474660
     [Google Scholar]
  42. PetrosilloG. PortincasaP. GrattaglianoI. CasanovaG. MateraM. RuggieroF.M. FerriD. ParadiesG. Mitochondrial dysfunction in rat with nonalcoholic fatty liver Involvement of complex I, reactive oxygen species and cardiolipin.Biochim. Biophys. Acta20071767101260126710.1016/j.bbabio.2007.07.01117900521
     [Google Scholar]
  43. ThomasC. PellicciariR. PruzanskiM. AuwerxJ. SchoonjansK. Targeting bile-acid signalling for metabolic diseases.Nat. Rev. Drug Discov.20087867869310.1038/nrd261918670431
     [Google Scholar]
  44. ZhuY. LiuH. ZhangM. GuoG.L. Fatty liver diseases, bile acids, and FXR.Acta Pharm. Sin. B20166540941210.1016/j.apsb.2016.07.00827709009
     [Google Scholar]
  45. LiY. JadhavK. ZhangY. Bile acid receptors in non-alcoholic fatty liver disease.Biochem. Pharmacol.201386111517152410.1016/j.bcp.2013.08.01523988487
     [Google Scholar]
  46. SousaT. CastroR.E. PintoS.N. CoutinhoA. LucasS.D. MoreiraR. RodriguesC.M. PrietoM. FernandesF. Deoxycholic acid modulates cell death signaling through changes in mitochondrial membrane properties.J. Lipid Res.201556112158217110.1194/jlr.M06265326351365
     [Google Scholar]
  47. ChenY.S. LiuH.M. LeeT.Y. Ursodeoxycholic acid regulates hepatic energy homeostasis and white adipose tissue macrophages polarization in leptin-deficiency obese mice.Cells201983E25310.3390/cells803025330884843
     [Google Scholar]
  48. TraussniggS. SchattenbergJ.M. DemirM. WiegandJ. GeierA. TeuberG. HofmannW.P. KremerA.E. SpredaF. KluweJ. PetersenJ. BoettlerT. RainerF. HalilbasicE. GreinwaldR. PrölsM. MannsM.P. FickertP. TraunerM. Austrian/German NAFLD-norUDCA study groupNorursodeoxycholic acid versus placebo in the treatment of non-alcoholic fatty liver disease: a double-blind, randomised, placebo-controlled, phase 2 dose-finding trial.Lancet Gastroenterol. Hepatol.201941078179310.1016/S2468‑1253(19)30184‑031345778
     [Google Scholar]
  49. CalkinA.C. TontonozP. Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR.Nat. Rev. Mol. Cell Biol.201213421322410.1038/nrm331222414897
     [Google Scholar]
  50. de Aguiar VallimT.Q. TarlingE.J. EdwardsP.A. Pleiotropic roles of bile acids in metabolism.Cell Metab.201317565766910.1016/j.cmet.2013.03.01323602448
     [Google Scholar]
  51. SafadiR. KonikoffF. M. MahamidM. Zelber-SagiS. HalpernM. GilatT. OrenR. The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association201412122085-2091.e1
     [Google Scholar]
  52. PockrosP.J. FuchsM. FreilichB. SchiffE. KohliA. LawitzE.J. HellsternP.A. Owens-GrilloJ. Van BieneC. ShringarpureR. MacConellL. ShapiroD. CohenD.E. CONTROL: A randomized phase 2 study of obeticholic acid and atorvastatin on lipoproteins in nonalcoholic steatohepatitis patients.Liver Int.201939112082209310.1111/liv.1420931402538
     [Google Scholar]
/content/journals/ijghd/10.2174/2666290601666210421132727
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Deoxycholic and Ursodeoxycholic Acid Differentially Impact Cellular Steatosis and Lipid Peroxidation in Cultured Hepatoma Cells
Int J Gastroenterol Hepatol Dis 1, e210421192957 (2022); https://doi.org/10.2174/2666290601666210421132727
/content/journals/ijghd/10.2174/2666290601666210421132727
/content/journals/ijghd/10.2174/2666290601666210421132727
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  • Article Type:     Research Article
Keyword(s): antioxidant effect; Bile acids; hepatic steatosis; lipid dysmetabolism; non-alcoholic fatty liver disease; oxidative stress

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