Molecular Neurobiology

, Volume 47, Issue 3, pp 1066–1080 | Cite as

Neuroprotective Effects of Resveratrol Against Aβ Administration in Rats are Improved by Lipid-Core Nanocapsules

  • Rudimar L. FrozzaEmail author
  • Andressa Bernardi
  • Juliana B. Hoppe
  • André B. Meneghetti
  • Aline Matté
  • Ana M. O. Battastini
  • Adriana R. Pohlmann
  • Sílvia S. Guterres
  • Christianne Salbego


Alzheimer’s disease (AD), a neurodegenerative disorder exhibiting a gradual decline in cognitive function, is characterized by the presence of neuritic plaques composed of neurofibrillary tangles and amyloid-β (Aβ) peptide. Available drugs for AD therapy have small effect sizes and do not alter disease progression. Several studies have been shown that resveratrol is associated with anti-amyloidogenic properties, but therapeutic application of its beneficial effects is limited. Here we compared the neuroprotective effects of free resveratrol treatment with those of resveratrol-loaded lipid-core nanocapsule treatment against intracerebroventricular injection of Aβ1-42 in rats. Animals received a single intracerebroventricular injection of Aβ1-42 (2 nmol), and 1 day after Aβ infusion, they were administered either free resveratrol (RSV) or resveratrol-loaded lipid-core nanocapsules (5 mg/kg, each 12 h, intraperitoneally), for 14 days. Aβ1-42-infused animals showed a significant impairment on learning memory ability, which was paralleled by a significant decrease in hippocampal synaptophysin levels. Furthermore, animals exhibited activated astrocytes and microglial cells, as well as disturbance in c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-3β (GSK-3β) activation, beyond destabilization of β-catenin levels. Our results clearly show that by using lipid-core nanocapsules, resveratrol was able to rescue the deleterious effects of Aβ1-42 while treatment with RSV presented only partial beneficial effects. These findings might be explained by the robust increase of resveratrol concentration in the brain tissue achieved by lipid-core nanocapsules. Our data not only confirm the potential of resveratrol in treating AD but also offer an effective way to improve the efficiency of resveratrol through the use of nanodrug delivery systems.


Alzheimer’s disease Amyloid-β peptide Drug delivery Hippocampus Neuroprotection Resveratrol 



This study was supported by the following Brazilian agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). The authors thank PRONEX CNPq-FAPERGS (#10/0048-4). RL Frozza and JB Hoppe were recipients of Brazilian CNPq fellowships. A Bernardi was the recipient of a CAPES Post-doctoral fellowship.


  1. 1.
    Mattson MP (2004) Pathways towards and away from Alzheimer’s disease. Nature 430:631–639PubMedCrossRefGoogle Scholar
  2. 2.
    Klein WL, Stine WB Jr, Teplow DB (2004) Small assemblies of unmodified amyloid beta-protein are the proximate neurotoxin in Alzheimer’s disease. Neurobiol Aging 25:569–580PubMedCrossRefGoogle Scholar
  3. 3.
    Walsh DM, Selkoe DJ (2004) Deciphering the molecular basis of memory failure in Alzheimer’s disease. Neuron 44:181–193PubMedCrossRefGoogle Scholar
  4. 4.
    Pardridge WM (2005) The blood–brain barrier: bottleneck in brain drug development. NeuroRx 2:3–14PubMedCrossRefGoogle Scholar
  5. 5.
    Modi G, Pillay V, Choonara YE, Ndesendo VMK, du Toit LC, Naidoo D (2009) Nanotechnological applications for the treatment of neurodegenerative disorders. Progress Neurobiol 88:272–285CrossRefGoogle Scholar
  6. 6.
    Hans ML, Lowman AM (2002) Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 6:319–327CrossRefGoogle Scholar
  7. 7.
    Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE (2001) Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70:1–20PubMedCrossRefGoogle Scholar
  8. 8.
    Zensi A, Begley D, Pontikis C, Legros C, Mihoreanu L, Wagner S, Büchel C, von Briesen H, Kreuter J (2009) Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurons. J Control Release 137:78–86PubMedCrossRefGoogle Scholar
  9. 9.
    Brasnjevic I, Steinbusch HWM, Schmitz C, Martinez-Martinez P (2009) Delivery of peptide and protein drugs over the blood–brain barrier. Progress Neurobiol 87:212–251CrossRefGoogle Scholar
  10. 10.
    Wilson B, Samanta MK, Santhi K, Kumar KPS, Ramasamy M, Suresh B (2010) Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine. Nanomedicine 6:144–152PubMedCrossRefGoogle Scholar
  11. 11.
    Guterres SS, Weiss V, de Luca Freitas L, Pohlmann AR (2000) Influence of benzyl benzoate as oil core on the physicochemical properties of spray-dried powders from polymeric nanocapsules containing indomethacin. Drug Deliv 7:195–199PubMedCrossRefGoogle Scholar
  12. 12.
    Pohlmann AR, Soares LU, Cruz L, Da Silveira NP, Guterres SS (2004) Diffusion and mathematical modeling of release profiles from nanocarriers. Curr Drug Deliv 1:103–110PubMedCrossRefGoogle Scholar
  13. 13.
    Beck RCR, Pohlmann AR, Hoffmeister C, Gallas MR, Collnot E, Schaefer UF, Guterres SS, Lehr CM (2007) Dexamethasone-loaded nanoparticle-coated microparticles: correlation between in vitro drug release and drug transport across Caco-2 cell monolayers. Eur J Pharm Biopharm 67:8–30CrossRefGoogle Scholar
  14. 14.
    Pohlmann AR, Mezzalira G, Venturini C, Cruz L, Bernardi A, Jäger E, Battastini AMO, Silveira NP, Guterres SS (2008) Determining the simultaneous presence of drug nanocrystals in drug-loaded polymeric nanocapsule aqueous suspensions: a relation between light scattering and drug content. Int J Pharmac 359:288–293CrossRefGoogle Scholar
  15. 15.
    Bernardi A, Braganhol E, Jäger E, Figueiró F, Edelweiss MI, Pohlmann AR, Guterres SS, Battastini AMO (2009) Indomethacin-loaded nanocapsules treatment reduces in vivo glioblastoma growth in a rat glioma model. Cancer Lett 281:53–63PubMedCrossRefGoogle Scholar
  16. 16.
    Frozza RL, Bernardi A, Paese K, Hoppe JB, da Silva T, Battastini AMO, Pohlmann AR, Guterres SS, Salbego C (2010) Characterization of trans-resveratrol-loaded lipid-core nanocapsules and tissue distribution studies in rats. J Biomed Nanotechnol 6:694–703PubMedCrossRefGoogle Scholar
  17. 17.
    Bernardi A, Frozza RL, Meneghetti A, Hoppe JB, Battastini AM, Pohlmann AR, Guterres SS, Salbego CG (2012) Indomethacin-loaded lipid-core nanocapsules reduce the damage triggered by Aβ1-42 in Alzheimer’s disease models. Int J Nanomedicine 7:4927–4942PubMedCrossRefGoogle Scholar
  18. 18.
    Orgogozo JM, Dartigues JF, Lafont S, Letenneur L, Commenges D, Salomon R, Renaud S, Breteler MB (1997) Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol 153:185–192PubMedGoogle Scholar
  19. 19.
    Lindsay J, Laurin D, Verreault R, Hébert R, Helliwell B, Hill GB, McDowell I (2002) Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol 156:445–453PubMedCrossRefGoogle Scholar
  20. 20.
    Vingtdeux V, Dreses-Werringloer U, Zhao H, Davies P, Marambaud P (2008) Therapeutic potential of resveratrol in Alzheimer's disease. BMC Neurosci 9(Suppl 2):S6, ReviewPubMedCrossRefGoogle Scholar
  21. 21.
    Anekonda TS (2006) Resveratrol-A boon for treating Alzheimer's disease? Brain Res Rev 52:316–326PubMedCrossRefGoogle Scholar
  22. 22.
    Harikumar KB, Aggarwal BB (2008) Resveratrol A multi-targeted agent for age-associated chronic diseases. Cell Cycle 8:1020–1035CrossRefGoogle Scholar
  23. 23.
    Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5:493–506PubMedCrossRefGoogle Scholar
  24. 24.
    Marambaud P, Zhao H, Davies P (2005) Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides. J Biol Chem 280:37377–37382PubMedCrossRefGoogle Scholar
  25. 25.
    Karuppagounder SS, Pinto JT, Xu H, Chen HL, Beal MF, Gibson GE (2009) Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease. Neurochem Int 54:111–118PubMedCrossRefGoogle Scholar
  26. 26.
    Vingtdeux V, Giliberto L, Zhao H, Chandakkar P, Wu Q, Simon JE, Janle EM, Lobo J, Ferruzzi MG, Davies P, Marambaud P (2010) AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-beta peptide metabolism. J Biol Chem 285:9100–9113PubMedCrossRefGoogle Scholar
  27. 27.
    Kundu JK, Surh Y-J (2008) Cancer chemopreventive and therapeutic potential of resveratrol: mechanistic perspectives. Cancer Lett 296:243–261CrossRefGoogle Scholar
  28. 28.
    Knutson MD, Leeuwenburgh C (2008) Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases. Nutr Rev 66:591–596PubMedCrossRefGoogle Scholar
  29. 29.
    Albani D, Polito L, Forloni G (2010) Sirtuins as novel targets for Alzheimer's disease and other neurodegenerative disorders: experimental and genetic evidence. J Alzheimers Dis 19:11–26PubMedGoogle Scholar
  30. 30.
    Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342PubMedCrossRefGoogle Scholar
  31. 31.
    Wenzel E, Somoza V (2005) Metabolism and bioavailability of trans-resveratrol. Mol Nutr Food Res 49:472–481PubMedCrossRefGoogle Scholar
  32. 32.
    Amri A, Chaumeil JC, Sfar S, Charrueau C (2012) Administration of resveratrol: what formulation solutions to bioavailability limitations? J Control Release 158:182–193PubMedCrossRefGoogle Scholar
  33. 33.
    Jäger E, Venturini CG, Poletto FS, Colomé LM, Pohlmann JPU, Bernardi A, Battastini AMO, Guterres SS, Pohlmann AR (2009) Sustained release from lipid-core nanocapsules by varying the core viscosity and the particle surface area. J Biomed Nanotechnol 5:130–140PubMedCrossRefGoogle Scholar
  34. 34.
    Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates, 5th edn. Elsevier Academic, San DiegoGoogle Scholar
  35. 35.
    Huges RN (2004) The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory. Neurosci Biobehav Rev 28:497–505CrossRefGoogle Scholar
  36. 36.
    Bevins RA, Besheer J (2006) Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study ‘recognition memory’. Nat Protocols 1:1306–1311CrossRefGoogle Scholar
  37. 37.
    Ennaceur A, Delacour J (1988) A new one-trial test for neurobiological studies of memory in rats. 1. Behavioral data. Behav Brain Res 31:47–59PubMedCrossRefGoogle Scholar
  38. 38.
    Peterson GL (1979) Review of the Folin-phenol protein quantification method of Lowry, Rosebrough, Farr and Randall. Anal Biochem 100:201–220PubMedCrossRefGoogle Scholar
  39. 39.
    Zamin LL, Dillenburg-Pilla P, Argenta-Comiran R, Horn AP, Simão F, Nassif M, Gerhardt D, Frozza RL, Salbego C (2006) Protective effect of resveratrol against oxygen–glucose deprivation in organotypic hippocampal slice cultures: involvement of PI3-K pathway. Neurobiol Dis 24:170–182PubMedCrossRefGoogle Scholar
  40. 40.
    Garrido JL, Godoy J, Alvarez A, Bronfman M, Inestrosa NC (2002) Protein kinase C inhibits amyloid β-peptide neurotoxicity by acting on members of the Wnt pathway. FASEB J 14:1982–1984Google Scholar
  41. 41.
    De Ferrari GV, Chacón MA, Barría MI, Garrido JL, Godoy JA, Olivares G, Reyes AE, Alvarez A, Bronfman M, Inestrosa NC (2003) Activation of Wnt signaling rescues neurodegeneration and behavioral impairments induced by β-amyloid fibrils. Mol Psychiatry 8:195–208PubMedCrossRefGoogle Scholar
  42. 42.
    Li B, Zhong L, Yang X, Andersson T, Huang M, Tang S-J (2011) WNT5A signaling contributes to Aβ-induced neuroinflammation and neurotoxicity. PlosOne 6:1–10Google Scholar
  43. 43.
    Woodruff-Pak DS (2008) Animal models of Alzheimer’s disease: therapeutic implications. J Alzheimers Dis 15:507–521PubMedGoogle Scholar
  44. 44.
    Ferreira ST, Vieira MN, De Felice FG (2007) Soluble protein oligomers as emerging toxins in Alzheimer’s and others amyloid diseases. IUBMB Life 59:332–345PubMedCrossRefGoogle Scholar
  45. 45.
    Knobloch M, Mansuy IM (2008) Dendritic spine loss and synaptic alterations in Alzheimer’s disease. Mol Neurobiol 37:73–82PubMedCrossRefGoogle Scholar
  46. 46.
    Broadbent NJ, Gaskin S, Squire LR, Clark RE (2010) Object recognition memory and the rodent hippocampus. Learn Mem 17:5–11PubMedCrossRefGoogle Scholar
  47. 47.
    Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 27:1372–1384PubMedCrossRefGoogle Scholar
  48. 48.
    Medeiros R, Prediger RDS, Passos GF, Pandolfo P, Duarte FS, Franco JL, Dafre AL, Di Giunta G, Figueiredo CP, Takahashi RN, Campos MM, Calixto JB (2007) Connecting TNF-α signaling pathways to iNOS expression in a mouse model of Alzheimer’s disease: relevance for the behavioral and synaptic deficits induced by amyloid β protein. J Neurosci 27:5394–5404PubMedCrossRefGoogle Scholar
  49. 49.
    Canas PM, Porciúncula LO, Cunha GMA, Silva CG, Machado NJ, Oliveira JMA, Oliveira CR, Cunha RA (2009) Adenosine A2A receptor blockade prevents synaptotoxicity and memory dysfunction caused by β-amyloid peptides via p38 mitogen-activated protein kinase pathway. J Neurosci 29:14741–14751PubMedCrossRefGoogle Scholar
  50. 50.
    Passos GF, Figueiredo CP, Prediger RDS, Pandolfo P, Duarte FS, Medeiros R, Calixto JB (2009) Role of the macrophage inflammatory protein-1α/CC chemokine receptor 5 signaling pathway in the neuroinflammatory response and cognitive deficits induced by β-amyloid peptide. Am J Pathol 175:1586–1597PubMedCrossRefGoogle Scholar
  51. 51.
    Bernardi A, Zilberstein AC, Jäger E, Campos MM, Morrone FB, Calixto JB, Pohlmann AR, Guterres SS, Battastini AMO (2009) Effects of indomethacin-loaded nanocapsules in experimental model of inflammation in rats. Br J Pharmacol 158:1104–1111PubMedCrossRefGoogle Scholar
  52. 52.
    Bernardi A, Frozza RL, Horn AP, Campos MM, Calixto JB, Salbego C, Pohlmann AR, Guterres SS, Battastini AMO (2010) Protective effects of indomethacin-loaded nanocapsules against oxygen–glucose deprivation in organotypic hippocampal slice cultures: involvement of neuroinflammation. Neurochem Int 57:629–636PubMedCrossRefGoogle Scholar
  53. 53.
    Calamini B, Ratia K, Malkowski MG, Cuendet M, Pezzuto JM, Santarsiero BD, Mesecar AD (2010) Pleiotropic mechanisms facilitated by resveratrol and its metabolites. Biochem J 429(2):273–282PubMedCrossRefGoogle Scholar
  54. 54.
    Hoshino J, Park EJ, Kondratyuk TP, Marler L, Pezzuto JM, van Breemen RB, Mo S, Li Y, Cushman M (2010) Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites. J Med Chem 53(13):5033–5043PubMedCrossRefGoogle Scholar
  55. 55.
    Miksits M, Wlcek K, Svoboda M, Kunert O, Haslinger E, Thalhammer T, Szekeres T, Jäger W (2009) Antitumor activity of resveratrol and its sulfated metabolites against human breast cancer cells. Planta Med 75(11):1227–1230PubMedCrossRefGoogle Scholar
  56. 56.
    Walle T (2011) Biovailability of resveratrol. Ann NY Acad Sci 1215:9–15PubMedCrossRefGoogle Scholar
  57. 57.
    Kreuter J, Alyautdin RN, Kharkevich DA, Ivanov AA (1995) Passage of peptides through the blood–brain barrier with colloidal polymer particles (nanoparticles). Brain Res 674:171–174PubMedCrossRefGoogle Scholar
  58. 58.
    Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharkevich DA, Kreuter J (1997) Delivery of loperamide across the blood–brain barrier with polysorbate 80-coated poly(butylcyanoacrylate) nanoparticles. Pharm Res 14:325–328PubMedCrossRefGoogle Scholar
  59. 59.
    Gulyaev AE, Gelperina SE, Skidan IN, Antropov AS, Kivman GY, Kreuter J (1999) Significant transport of doxorubicin into the brain with polysorbate 80-coated nanoparticles. Pharm Res 16:1564–1569Google Scholar
  60. 60.
    Lue L-F, Kuo Y-M, Beach T, Walker DG (2010) Microglia activation and anti-inflammatory regulation in Alzheimer’s disease. Mol Neurobiol 41:115–128PubMedCrossRefGoogle Scholar
  61. 61.
    Hensley K (2010) Neuroinflammation in Alzheimer’s disease: mechanisms, pathologic consequences, and potential for therapeutic manipulation. J Alzheimers Dis 21:1–14PubMedGoogle Scholar
  62. 62.
    Garwood CJ, Pooler AM, Atherton J, Hanger DP, Noble W (2011) Astrocytes are important mediators of Aβ-induced neurotoxicity and tau phosphorylation in primary culture. Cell Death Dis 2:1–9CrossRefGoogle Scholar
  63. 63.
    Capiralla H, Vingtdeux V, Zhao H, Sankowski R, Al-Abed Y, Davies P, Marambaud P (2011) Resveratrol mitigates lipopolysaccharide- and Aβ-mediated microglial inflammation by inhibiting the TLR4/NF-κB/STAT signaling cascade. J Neurochem 120:461–472PubMedCrossRefGoogle Scholar
  64. 64.
    Mehan S, Meena H, Sharma D, Sankhla R (2011) JNK: a stress-activated protein kinase therapeutic strategies and involvement in Alzheimer’s and various neurodegenerative abnormalities. J Mol Neurosci 43:376–390PubMedCrossRefGoogle Scholar
  65. 65.
    Waetzig V, Herdegen T (2004) Neurodegenerative and physiological actions of c-Jun N-terminal kinases in the mammalian brain. Neurosci Lett 361:64–67PubMedCrossRefGoogle Scholar
  66. 66.
    Ploia C, Antoniou X, Sclip A, Grande V, Cardinetti D, Colombo A, Canu N, Benussi L, Ghidoni R, Forloni G, Borsello T (2011) JNK plays a key role in tau hyperphosphorylation in Alzheimer’s disease models. J Alzheimers Dis 26:315–329PubMedGoogle Scholar
  67. 67.
    Balaraman Y, Limaye AR, Levey AI, Srinivasan S (2006) Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance. Cell Mol Life Sci 63:1226–1235PubMedCrossRefGoogle Scholar
  68. 68.
    Hall AC, Lucas FR, Salinas PC (2000) Axonal remodeling and synaptic differentiation in the cerebellum is regulated by Wnt-7a signaling. Cell 100:525–535PubMedCrossRefGoogle Scholar
  69. 69.
    Cadigan KM, Nusse R (1997) Wnt signaling: a common theme in animal development. Genes Dev 11:3286–3305PubMedCrossRefGoogle Scholar
  70. 70.
    Lee SM, Tole S, Grove E, McMahon AP (2000) A local Wnt-3a signal is required for development of the mammalian hippocampus. Development 127:457–467PubMedGoogle Scholar
  71. 71.
    Galceran J, Miyashita-Lin EM, Devaney E, Rubenstein JL, Grosschedl R (2000) Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1. Development 127:469–482PubMedGoogle Scholar
  72. 72.
    Liu C, Li Y, Semenov M, Han C, Baeg C, Tan Y, Zhang Z, Lin X, He X (2002) Control of β-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108:837–847PubMedCrossRefGoogle Scholar
  73. 73.
    Inestrosa NC, Varela-Nallar L, Grabowski CP, Colombres M (2007) Synaptotoxicity in Alzheimer’s disease: the Wnt signaling pathway as a molecular target. IUBMB Life 59:316–321PubMedCrossRefGoogle Scholar
  74. 74.
    Toledo EM, Inestrosa NC (2009) Activation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1DeltaE9 mouse model of Alzheimer’s disease. Mol Psychiatry 15:272–285PubMedCrossRefGoogle Scholar
  75. 75.
    Ge J-F, Qiao J-P, Qi C-C, Wang C-W, Zhou J-N (2012) The binding of resveratrol to monomer and fibril amyloid beta. Neurochem Int 61:1192–1201PubMedCrossRefGoogle Scholar
  76. 76.
    Ladiwala ARA, Lin JC, Bale SS, Marcelino-Cruz AM, Bhattacharya M, Dordick JS, Tessier PM (2010) Resveratrol selectively remodels soluble oligomers and fibrils of amyloid Aβ into off-pathway conformers. J Biol Chem 285:24228–24237PubMedCrossRefGoogle Scholar
  77. 77.
    Selkoe DJ (2011) Resolving controversies on the path to Alzheimer’s therapeutics. Nat Med 17(9):1060–1065PubMedCrossRefGoogle Scholar
  78. 78.
    Mucke L, Selkoe DJ (2012) Neurotoxicity of amyloid β-protein: synaptic and network dysfunction. Cold Spring Harb Perspect Med 2(7):a006338PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Rudimar L. Frozza
    • 1
    Email author
  • Andressa Bernardi
    • 2
  • Juliana B. Hoppe
    • 1
  • André B. Meneghetti
    • 1
  • Aline Matté
    • 1
  • Ana M. O. Battastini
    • 1
  • Adriana R. Pohlmann
    • 3
  • Sílvia S. Guterres
    • 2
  • Christianne Salbego
    • 1
  1. 1.Programa de Pós-Graduação em Bioquímica, Departamento de BioquímicaUniversidade Federal do Rio Grande do Sul—UFRGSPorto AlegreBrazil
  2. 2.Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de FarmáciaUniversidade Federal do Rio Grande do Sul—UFRGSPorto AlegreBrazil
  3. 3.Programa de Pós-Graduação em Química, Instituto de QuímicaUniversidade Federal do Rio Grande do Sul—UFRGSPorto AlegreBrazil

Personalised recommendations