Skip to main content

Advertisement

Log in

Carbon Tetrachloride Increases the Pro-inflammatory Cytokines Levels in Different Brain Areas of Wistar Rats: The Protective Effect of Acai Frozen Pulp

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Acai offers health benefits associated with its high antioxidante capacity, phytochemical composition, nutritional and sensory value. Therefore, the objective of this study was to evaluate the protective effect of acai frozen pulp on carbon tetrachloride (CCl4)-induced damage via modulation of anti- and pro-inflammatory cytokines in rat brain tissue. The rats were treated via oral (gavage) daily with water or acai frozen pulp for 14 days at a dose of 7 μL/g. On the 15th day, the animals in each group received a single intraperitoneal injection of CCl4 in a dose of 3.0 mL/kg or the same volume of mineral oil. After 4 h, the animals were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum were dissected and homogenated to evaluate the levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), interleukin 18 (IL-18), interleukin 6 (IL-6) and interleukin 10 (IL-10). Data were statistically analyzed by analysis of variance followed by the Tukey post hoc test. It was observed that CCl4 increased TNF-α, IL-1β and IL-18 levels in all brain tissues, and that acai frozen pulp was able to prevent this increase. IL-6 and IL-10 brain tissue levels remained unchanged during all treatments. CCl4 experimental model was suitable to investigate brain tissue anti and pro-inflammatory cytokines. Acai frozen pulp prevented an increase in IL-1β, IL-18 and TNF-α, while IL-6 and IL-10 levels remained unchanged. The precise pathway by which inflammation contribute to hepatic encephalopathy, as well as to how this pathway can be modulated, is still under investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Webster LT, Gabuzda GJ (1957) Ammonium uptake by the extremities and brain in hepatic coma. J Clin Investig 50:414–424. doi:10.1172/JCI103621

    Google Scholar 

  2. Häussinger D, Sies H (2013) Hepatic encephalopathy: clinical aspects and pathogenetic concept. Arch Biochem Biophys 536:97–100. doi:10.1016/j.abb.2013.04.013

    Article  PubMed  Google Scholar 

  3. McDermott WV (1958) The role of ammonia intoxication in hepatic coma. Bull NY Acad Med 34:357–365

    Google Scholar 

  4. Shawcross DL, Sharifi Y, Canavan JB, Yeoman AD, Abeles RD, Taylor NJ, Auzinger G, Bernal W, Wendon JA (2011) Infection and systemic inflammation, not ammonia, are associated with grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis. J Hepatol 54:640–649. doi:10.1016/j.jhep.2010.07.045

    Article  CAS  PubMed  Google Scholar 

  5. Acharya SK, Bhatia V, Sreenivas V, Khanal S, Panda SK (2009) Efficacy of l-ornithine l-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study. Gastroenterology 136:2159–2168. doi:10.1053/j.gastro

    Article  CAS  PubMed  Google Scholar 

  6. Cichoż-lach H, Michalak A (2013) Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. World J Gastroenterol 19:26–34. doi:10.3748/wjg.v19.i1.26

    Article  PubMed Central  PubMed  Google Scholar 

  7. Butterworth RF (2000) Hepatic encephalopathy: a neuropsychiatric disorder involving multiple neurotransmitter systems. Curr Opin Neurol 6:721–727

    Article  Google Scholar 

  8. Bémeur C, Butterworth RF (2013) Liver-brain proinflammatory signalling in acute liver failure: role in the pathogenesis of hepatic encephalopathy and brain edema. Metab Brain Dis 28:145–150. doi:10.1007/s11011-012-9361-3

    Article  PubMed  Google Scholar 

  9. Lachmann V, Görg B, Bidmon HJ, Keitel V, Häussinger D (2013) Precipitants of hepatic encephalopathy induce rapid astrocyte swelling in an oxidative stress dependent manner. Arch Biochem Biophys 536:143–151. doi:10.1016/j.abb.2013.05.004

    Article  CAS  PubMed  Google Scholar 

  10. Jimenez W, Clària J, Arroyo V, Rodés J (1992) Carbon tetrachloride induced cirrhosis in rats: an useful tool for investigating the patogenesis in chronic liver disease. J Gastroenterol Hepatol 7:90–97. doi:10.1111/j.1440-1746.1992.tb00940

    Article  CAS  PubMed  Google Scholar 

  11. Basu S (2003) Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients. Toxicology 189:113–127. doi:10.1016/S0300-483X(03)00157-4

    Article  CAS  PubMed  Google Scholar 

  12. Tirkey N, Pilkhawl S, Kuhad A, Chopra K (2005) Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney. BMC Pharmacol 5:1–8. doi:10.1186/1471-2210-5-2

    Google Scholar 

  13. Rocha SW, de França ME, Rodrigues GB, Barbosa KP, Nunes AK, Pastor AF, Oliveira AG, Oliveira WH, Luna RL, Peixoto CA (2014) Diethylcarbamazine reduces chronic inflammation and fibrosis in carbon tetrachloride-(CCl4) induced liver injury in mice. Mediators Inflamm 2014:696383. doi:10.1155/2014/696383

    PubMed Central  PubMed  Google Scholar 

  14. Dai Q, Borenstein AR, Jackson JC, Larson EB (2006) Fruit and vegetable juices and Alzheimer’s disease: the Kame Project. Am J Med 119:751–759. doi:10.1016/j.amjmed.2006.03.045

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Goodwin JS, Brodwick M (1995) Diet, aging, and cancer. Clin Geriatr Med 11:577–589

    CAS  PubMed  Google Scholar 

  16. Heo HJ, Choi SJ, Choi SG, Shin DH, Lee JM, Lee CY (2008) Effects of banana, orange, and apple on oxidative stress-induced neuro-toxicity in PC12 cells. J Food Sci 73:28–32. doi:10.1111/j.1750-3841.2007.00632.x

    Article  Google Scholar 

  17. Kohlmeier L, Simonsen N, Mottus K (1995) Dietary modifiers of carcinogenics. Environ Health Perspect 103:177–184. doi:10.1289/ehp.95103s8177

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Silalahi J (2002) Anticancer and health protective properties of citrus fruit components. Asia Pac J Clin Nutr 11:79–84. doi:10.1046/j.1440-6047.2002.00271.x

    Article  CAS  PubMed  Google Scholar 

  19. Steinmetz KA, Potter JD (1996) Vegetables, fruits, and cancer prevention: a review. J Am Assoc 96:1027–1039. doi:10.1016/S0002-8223(96)00273-8

    CAS  Google Scholar 

  20. Schauss AG, Wu X, Prior RL, Ou B, Patel D, Huang D, Kanabick JP (2006) Phytochemical and nutrient composition of the freeze-dried amazonian palm berry, Euterpe oleraceae mart. (acai). J Agric Food Chem 54:8598–8603. doi:10.1021/jf060976g

    Article  CAS  PubMed  Google Scholar 

  21. Bramanti V, Tomassoni D, Bronzi D, Grasso S, Currò M, Avitabile M, Li Volsi G, Renis M, Ientile R, Amenta F, Avola R (2010) Alpha-lipoic acid modulates GFAP, vimentin, nestin, cyclin D1 and MAP-kinase espression in astroglial cell cultures. Neurochem Res 35:2070–2077. doi:10.1007/s11064-010-0256-6

    Article  CAS  PubMed  Google Scholar 

  22. Gabardo T, Pripolli CM, Andrade RB, Gemelli T, Lima JDO, Oliveira AS, Medeiros NS, Wannmacher C, Dani C, Funchal C (2015) Assessment of changes in energy metabolism parameters provoked by carbon tetrachloride in Wistar rats and the protective effect of white grape juice. Toxicol Rep 2:645–653. doi:10.1016/j.toxrep.2015.03.011

    Article  Google Scholar 

  23. Grasso S, Bramanti V, Tomassoni D, Bronzi D, Malfa G, Traini E, Napoli M, Renis M, Amenta F, Avola R (2014) Effect of lipoic acid and α-glyceryl-phosphoryl-choline on astroglial cell proliferation and differentiation in primary culture. J Neurosci Res 92:86–94. doi:10.1002/jnr.23289

    Article  CAS  PubMed  Google Scholar 

  24. Kramer K, Packer L, Hoppe P (2001) R-alpha-lipoic acid. Nutraceuticals in health and disease prevention. Marcel Dekker Inc, New York, pp 129–164

    Google Scholar 

  25. Nair V, Bang WY, Schreckinger E, Andarwulan N, Cisneros-Zevallos L (2015) The protective role of ternatin anthocyanins and quercetin glycosides from Butterfly Pea (Clitoria ternatea Leguminosae) Blue flower petals against LPS-induced inflammation in macrophage cells. J Agric Food Chem. doi:10.1021/acs.jafc.5b00928

    PubMed  Google Scholar 

  26. Menezes FS, Falcão DQ, de Mendonça Filho RFW, Silveira CS, Renno MN, Rodrigues VP, Moreira DL, Matheus ME, Fernandes PD, Kaplan MAC (2005) Chemical and pharmacological survey on Brazilian medicinal plants using ethnopharmacological information as a tool. Acta Hortic 675:89–95

    Google Scholar 

  27. EMBRAPA (BDPA) 2000. Available in: http://www.bdpa.cnptia.embrapa.br/busca?b=ad&id=346224&biblioteca=vazio&busca=autoria:%22H.%22&qFacets=autoria:%22H.%22&sort=&paginacao=t&paginaAtual=1. Accessed June 2014

  28. Spada PD, de Souza GG, Bortolini GV, Henriques JA, Salvador M (2008) Antioxidant, mutagenic, and antimutagenic activity of frozen fruits. J Med Food 11:144–151. doi:10.1089/jmf.2007.598

    Article  CAS  PubMed  Google Scholar 

  29. Sanabria N, Sangronis E (2007) Characterization of the acai or manaca (Euterpe oleracea Mart.): a fruit of the Amazon. Arch Latinoam Nutr 57:94–98

    Google Scholar 

  30. Spada PDS, Dani C, Bortolini GV, Funchal C, Henriques JAP, Salvador M (2009) Frozen fruit pulp of Euterpe oleraceae Mart. (Acai) prevents hydrogen peroxide-induced damage in the cerebral cortex, cerebellum, and hippocampus of rats. J Med Food 12:1084–1088. doi:10.1089/jmf.2008.0236

    Article  CAS  PubMed  Google Scholar 

  31. Xie C, Kang J, Li Z, Schauss AG, Badger TM, Nagarajan S, Wu T, Wu X (2012) The açaí flavonoid velutin is a potent anti-inflammatory agent: blockade of LPS-mediated TNF-α and IL-6 production through inhibiting NF-κB activation and MAPK pathway. J Nutr Biochem 23:1184–1191. doi:10.1016/j.jnutbio.2011.06.013

    Article  CAS  PubMed  Google Scholar 

  32. Lowry OH, Rosebrouh NJ, Lewis-Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. JBC. 193:265–275

    CAS  Google Scholar 

  33. Sherlock S (1958) Pathogenesis and management of hepatic coma. Am J Med 24:805–813. doi:10.1001/jama.1959.03000270058013

    Article  CAS  PubMed  Google Scholar 

  34. Bobermin LD, Quincozes-Santos A, Guerra MC, Leite MC, Souza DO, Gonçalves CA, Gottfried C (2012) Resveratrol prevents ammonia toxicity in astroglial cells. PLoS ONE 7:e52164. doi:10.1371/journal.pone.0052164

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Jayakumar AR, Bethea JR, Tong XY, Gomez J, Norenberg MD (2011) NF-κB in the mechanism of brain edema in acute liver failure: studies in transgenic mice. Neurobiol Dis 41:498–507. doi:10.1016/j.nbd.2010.10.021

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Rivera-Espinosa L, Floriano-Sánchez E, Pedraza-Chaverrí J, Coballase-Urrutia E, Sampieri AI, Ortega-Cuellar D, Cárdenas-Rodríguez N, Carmona-Aparicio L (2013) Contributions of microdialysis to new alternative therapeutics for hepatic encephalopathy. Int J Mol Sci 14:16184–16206. doi:10.3390/ijms140816184

    Article  PubMed Central  PubMed  Google Scholar 

  37. Sekhar MS, Unnikrishnan MK, Rodrigues GS, Mukhopadhyay C (2013) Synbiotic formulation of probiotic and lactulose combination for hepatic encephalopathy treatment: a realistic hope? Med Hypotheses 81:167–168. doi:10.1016/j.mehy.2013.05.016

    Article  CAS  PubMed  Google Scholar 

  38. Sharma P, Sharma BC (2013) Disaccharides in the treatment of hepatic encephalopathy. Metab Brain Dis 28:313–320. doi:10.1007/s11011-013-9392-4

    Article  CAS  PubMed  Google Scholar 

  39. Staziaki PV, Marques CM, Delattre AM, De Paula Cioni B, Rufino M, Dos Santos FV, Licks F, Marroni NP, Ferraz AC (2013) Fish oil has beneficial effects on behavior impairment and oxidative stress in rats subjected to a hepatic encephalopathy model. CNS Neurol Disord Drug Targets 12:84–93. doi:10.2174/1871527311312010014

    Article  CAS  PubMed  Google Scholar 

  40. Joseph JA, Ayyappan UP, Sasidharan SR, Mutyala S, Goudar KS, Agarwal A (2014) Ameliorative effect of Phytocee™ Cool against carbon tetrachloride-induced oxidative stress. Pharmacogn Res 6:320–325. doi:10.4103/0974-8490.138284

    Article  CAS  Google Scholar 

  41. Shin MO, Moon JO (2010) Effect of dietary supplementation of grape skin and seeds on liver fibrosis induced by dimethylnitrosamine in rats. Nutr Res Pract 4:369–374. doi:10.4162/nrp.2010.4.5.369

    Article  PubMed Central  PubMed  Google Scholar 

  42. Khoshbaten M, Aliasgarzadeh A, Masnadi K, Farhang S, Tarzamani MK, Babaei H, Kiani J, Zaare M, Najafipoor F (2010) Grape seed extract to improve liver function in patients with nonalcoholic fatty liver change. Saudi J Gastroenterol 16:194–197. doi:10.4103/1319-3767.65197

    Article  PubMed Central  PubMed  Google Scholar 

  43. Hazell AS, Butterworth RF (1999) Hepatic encephalopathy: an update of pathophysiologic mechanisms. Proc Soc Exp Biol Med 222:99–112

    Article  CAS  PubMed  Google Scholar 

  44. Coltart I, Tranah TH, Shawcross DL (2013) Inflammation and hepatic encephalopathy. Arch Biochem Biophys 536:189–196. doi:10.1016/j.abb.2013.03.016

    Article  CAS  PubMed  Google Scholar 

  45. Farina C, Aloisi F, Meinl E (2007) Astrocytes are active players in cerebral innate immunity. Trends Immunol 28:138–145. doi:10.1016/j.it.2007.01.005

    Article  CAS  PubMed  Google Scholar 

  46. Green HF, Nolan YM (2012) GSK-3 mediates the release of IL-1beta, TNF-alpha and IL-10 from cortical glia. Neurochem Int 61:666–671. doi:10.1016/j.neuint.2012.07.003

    Article  CAS  PubMed  Google Scholar 

  47. Hu D, Wan L, Chen M, Caudle Y, LeSage G, Li Q, Yin D (2014) Essential role of IL-10/STAT3 in chronic stress-induced immune suppression. Brain Behav Immun 36:118–127. doi:10.1016/j.bbi.2013.10.016

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Tanabe K, Matsushima-Nishiwaki R, Yamaguchi S, Iida H, Dohi S, Kozawa O (2010) Mechanisms of tumor necrosis factor-alpha-induced interleukin-6 synthesis in glioma cells. J Neuroinflamm 7:16. doi:10.1186/1742-2094-7-16

    Article  Google Scholar 

  49. de Rivero Vaccari JP, Dietrich WD, Keane RW (2014) Activation and regulation of cellular inflammasomes: gaps in our knowledge for central nervous system injury. J Cereb Blood Flow Metab 34:369–375. doi:10.1038/jcbfm.2013.227

    Article  PubMed Central  PubMed  Google Scholar 

  50. Bossu P, Ciaramella A, Salani F, Vanni D, Palladino I, Caltagirone C, Scapigliati G (2010) Interleukin-18, from neuroinflammation to Alzheimer’s disease. Curr Pharm Des 16:4213–4224. doi:10.2174/138161210794519147

    Article  CAS  PubMed  Google Scholar 

  51. Tranah TH, Vijay GK, Ryan JM, Shawcross DL (2013) Systemic inflammation and ammonia in hepatic encephalopathy. Metab Brain Dis 28:1–5. doi:10.1007/s11011-012-9370-2

    Article  CAS  PubMed  Google Scholar 

  52. Halim AB, El-Ahmady O, Hassab-Allah S, Abdel-Galil F, Hafez Y, Darwish A (1997) Biochemical effect of antioxidants on lipids and liver function in experimentally-induced liver damage. Ann Clin Biochem 34:656–663. doi:10.1177/000456329703400610

    Article  CAS  PubMed  Google Scholar 

  53. Sikander M, Malik S, Parveen K, Ahmad M, Yadav D, Hafeez ZB, Bansal M (2013) Hepatoprotective effect of Origanum vulgare in Wistar rats against carbon tetrachloride-induced hepatotoxicity. Protoplasma 250:483–493. doi:10.1007/s00709-012-0431-5

    Article  PubMed  Google Scholar 

  54. Yang X, Yang S, Guo Y, Jiao Y, Zhao Y (2013) Compositional characterisation of soluble apple polysaccharides, and their antioxidant and hepatoprotective effects on acute CCl4-caused liver damage in mice. Food Chem 138:1256–1264. doi:10.1016/j.foodchem.2012.10.030

    Article  CAS  PubMed  Google Scholar 

  55. Bellaver B, Souza DG, Souza DO, Quincozes-Santos A (2014) Resveratrol increases antioxidant defenses and decreases proinflammatory cytokines in hippocampal astrocyte cultures from newborn, adult and aged Wistar rats. Toxicol In Vitro 28:479–484. doi:10.1016/j.tiv.2014.01.006

    Article  CAS  PubMed  Google Scholar 

  56. Dani C, Oliboni LS, Umezu FM, Pasquali MAB, Salvador M, Moreira JCF, Henriques JAP (2009) Antioxidant and antigenotoxic activities of purple grape juice—organic and conventional—in adult rats. J Med Food 12:1111–1118. doi:10.1089/jmf.2008.0256

    Article  CAS  PubMed  Google Scholar 

  57. Kan S, Devi SA, Kawashima S (1991) Effect of vitamin E on the accumulation of fluorescent material in cultured cerebral cortical cells of mice. Exp Gerontol 26:365–374. doi:10.1016/0531-5565(91)90048-Q

    Article  CAS  PubMed  Google Scholar 

  58. Singh M, Arseneault M, Sanderson T, Murthy V, Ramassamy C (2008) Challenges for research on polyphenols from foods in Alzheimer’s disease: bioavailability, metabolism, and cellular and molecular mechanisms. J Agric Food Chem 56:4855–4873. doi:10.1021/jf0735073

    Article  CAS  PubMed  Google Scholar 

  59. Iaderoza M, Baldini VLS, Draetta SE, Bovi MLA (1992) Anthocyanins from fruits of açaí (Euterpeoleracea, Mart) and juçara (Euterpeedulis Mart). Trop Sci 32:41–46

    Google Scholar 

  60. Graf D, Seifert S, Bub A, Fröhling B, Dold S, Unger F, Römpp A, Watzl B (2013) Anthocyanin-rich juice does not affect gut-associated immunity in Fischer rats. Mol Nutr Food Res 57:1753–1761. doi:10.1002/mnfr.201300022

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by research grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and Centro Universitário Metodista – IPA.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cláudia Funchal.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Souza Machado, F., Marinho, J.P., Abujamra, A.L. et al. Carbon Tetrachloride Increases the Pro-inflammatory Cytokines Levels in Different Brain Areas of Wistar Rats: The Protective Effect of Acai Frozen Pulp. Neurochem Res 40, 1976–1983 (2015). https://doi.org/10.1007/s11064-015-1693-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-015-1693-z

Keywords

Navigation