Basic Research in Cardiology

, 114:38 | Cite as

Mitochondrial bioenergetics links inflammation and cardiac contractility in endotoxemia

  • Tamara Antonela Vico
  • Timoteo Marchini
  • Santiago Ginart
  • Mario Alejandro Lorenzetti
  • Juan Santiago Adán Areán
  • Valeria Calabró
  • Mariana Garcés
  • Mariana Cristina Ferrero
  • Tamara Mazo
  • Verónica D’Annunzio
  • Ricardo J. Gelpi
  • Daniel Corach
  • Pablo Evelson
  • Virginia VanascoEmail author
  • Silvia AlvarezEmail author
Original Contribution


There is current awareness about the central role of mitochondrial dysfunction in the development of cardiac dysfunction in systemic inflammatory syndromes, especially in sepsis and endotoxemia. The aim of this work was to elucidate the mechanism that governs the link between the severity of the systemic inflammatory insult and mitochondrial function, analysing the consequences on heart function, particularly in cardiac contractile state. Female Sprague–Dawley rats were subjected to low-grade endotoxemia (i.p. injection LPS 0.5 mg kg−1 body weight) and severe endotoxemia (i.p. injection LPS 8 mg kg−1 body weight) for 6 h. Blood NO, as well as cardiac TNF-α and IL-1β mRNA, were found increased as the severity of the endotoxemia increases. Cardiac relaxation was altered only in severe endotoxemia, although contractile and lusitropic reserves were found impaired in both treatments in response to work-overload. Cardiac ultrastructure showed disorientation of myofibrillar structure in both endotoxemia degrees, but mitochondrial swelling and cristae disruption were only observed in severe endotoxemia. Mitochondrial ATP production, O2 consumption and mitochondrial inner membrane potential decreases were related to blood NO levels and mitochondrial protein nitration, leading to diminished ATP availability and impairment of contractile state. Co-treatment with the NOS inhibitor l-NAME or the administration of the NO scavenger c-PTIO leads to the observation that mitochondrial bioenergetics status depends on the degree of the inflammatory insult mainly determined by blood NO levels. Unravelling the mechanisms involved in the onset of sepsis and endotoxemia improves the interpretation of the pathology, and provides new horizons for novel therapeutic targets.


Mitochondrial bioenergetics Cardiac dysfunction Systemic inflammation Endotoxemia Nitric oxide 



Adenosine triphosphate


Adenosine diphosphate


Bovine serum albumin


2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt








Nω-nitro-l-arginine methyl ester hydrochloride




Mitochondrial membranes


Nicotinamide adenine dinucleotide


Nitric oxide






Polymorphonuclear leukocytes


Respiratory control ratio


Reactive oxygen species


Tumor necrosis factor



The authors are grateful to Daniel Gonzalez Maglio for the helpful assistance with ELISA assays, to Elizabeth Robello for the assistance with EPR assays, and to Pablo La Padula for his helpful analysis of cardiac function.


This work was supported by research Grants from the Secretaría de Ciencia y Técnica, University of Buenos Aires [UBACYT2016 20020150100186BA]; Agencia Nacional de Promoción Científica y Tecnológica (ANPCYT) [PICT 2013-3227]; and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) [PIP 11220120100321].

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

395_2019_745_MOESM1_ESM.pdf (226 kb)
Supplementary material 1 (PDF 54 kb)


  1. 1.
    Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC, Der Poll T, Vincent JL, Angus DC (2016) The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315:801–810. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Cohen J, Vincent J-L, Adhikari NKJ, Machado FR, Angus DC, Calandra T, Jaton K, Giulieri S, Delaloye J, Opal S, Tracey K, van der Poll T, Pelfrene E (2015) Sepsis: a roadmap for future research. Lancet Infect Dis 15:581–614. CrossRefPubMedGoogle Scholar
  3. 3.
    Thimmulappa RK, Scollick C, Traore K, Yates M, Trush MA, Liby KT, Sporn MB, Yamamoto M, Kensler TW, Biswal S (2006) Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem Biophys Res Commun 351:883–889. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Morris MC, Gilliam EA, Li L (2014) Innate immune programing by endotoxin and its pathological consequences. Front Immunol 5:680. CrossRefPubMedGoogle Scholar
  5. 5.
    Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti J-FF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761–1772. CrossRefGoogle Scholar
  6. 6.
    Frisard MI, McMillan RP, Marchand J, Wahlberg KA, Wu Y, Voelker KA, Heilbronn L, Haynie K, Muoio B, Li L, Hulver MW (2010) Toll-like receptor 4 modulates skeletal muscle substrate metabolism. Am J Physiol Endocrinol Metab 298:E988–E998. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Glaros TG, Chang S, Gilliam EA, Maitra U, Deng H, Li L (2013) Causes and consequences of low grade endotoxemia and inflammatory diseases. Front Biosci (Schol Ed) 5:754–765. CrossRefGoogle Scholar
  8. 8.
    de Punder K, Pruimboom L (2015) Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability. Front Immunol 6:223. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Antonucci E, Fiaccadori E, Donadello K, Taccone FS, Franchi F, Scolletta S (2014) Myocardial depression in sepsis: from pathogenesis to clinical manifestations and treatment. J Crit Care 29:500–511. CrossRefPubMedGoogle Scholar
  10. 10.
    Celes MR, Prado CM, Rossi MA (2013) Sepsis: going to the heart of the matter. Pathobiology 80:70–86. CrossRefPubMedGoogle Scholar
  11. 11.
    Fernandes CJ Jr, de Assuncao MS (2012) Myocardial dysfunction in sepsis: a large, unsolved puzzle. Crit Care Res Pr 2012:896430. CrossRefGoogle Scholar
  12. 12.
    Kakihana Y, Ito T, Nakahara M, Yamaguchi K, Yasuda T (2016) Sepsis-induced myocardial dysfunction: pathophysiology and management. J Intensive Care 4:22. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, Davies NA, Cooper CE, Singer M (2002) Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 360:219–223. CrossRefPubMedGoogle Scholar
  14. 14.
    Carre JE, Orban JC, Re L, Felsmann K, Iffert W, Bauer M, Suliman HB, Piantadosi CA, Mayhew TM, Breen P, Stotz M, Singer M (2010) Survival in critical illness is associated with early activation of mitochondrial biogenesis. Am J Respir Crit Care Med 182:745–751. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Fink MP (2001) Cytopathic hypoxia. Mitochondrial dysfunction as mechanism contributing to organ dysfunction in sepsis. Crit Care Clin 17:219–237. CrossRefPubMedGoogle Scholar
  16. 16.
    Flierl M, Rittirsch D, Huber-Lang MS, Sarma JV, Ward PA (2008) Molecular events in the cardiomyopathy of sepsis. Mol Med 14:1. CrossRefGoogle Scholar
  17. 17.
    Radi R, Cassina A, Hodara R, Quijano C, Castro L (2002) Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med 33:1451–1464. CrossRefPubMedGoogle Scholar
  18. 18.
    Vanasco V, Saez T, Magnani ND, Pereyra L, Marchini T, Corach A, Vaccaro MI, Corach D, Evelson P, Alvarez S (2014) Cardiac mitochondrial biogenesis in endotoxemia is not accompanied by mitochondrial function recovery. Free Radic Biol Med 77:1–9. CrossRefPubMedGoogle Scholar
  19. 19.
    Bøtker HE, Hausenloy D, Andreadou I, Antonucci S, Boengler K, Davidson SM, Deshwal S, Devaux Y, Di Lisa F, Di Sante M, Efentakis P, Femminò S, García-Dorado D, Giricz Z, Ibanez B, Iliodromitis E, Kaludercic N, Kleinbongard P, Neuhäuser M, Ovize M, Pagliaro P, Rahbek-Schmidt M, Ruiz-Meana M, Schlüter K-D, Schulz R, Skyschally A, Wilder C, Yellon DM, Ferdinandy P, Heusch G (2018) Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection. Basic Res Cardiol 113:39. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Alvarez S, Vico T, Vanasco V (2016) Cardiac dysfunction, mitochondrial architecture, energy production, and inflammatory pathways: interrelated aspects in endotoxemia and sepsis. Int J Biochem Cell Biol 81:307–314. CrossRefPubMedGoogle Scholar
  21. 21.
    Yao Y, Hu X, Feng X, Zhao Y, Song M, Wang C, Fan H (2019) Dexmedetomidine alleviates lipopolysaccharide-induced acute kidney injury by inhibiting the NLRP3 inflammasome activation via regulating the TLR4/NOX4/NF-κB pathway. J Cell Biochem. CrossRefPubMedGoogle Scholar
  22. 22.
    Natanson C, Eichenholz PW, Danner RL, Eichacker PQ, Hoffman WD, Kuo GC, Banks SM, MacVittie TJ, Parrillo JE (1989) Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J Exp Med 169:823–832. CrossRefPubMedGoogle Scholar
  23. 23.
    Zhang H-X, Liu S-J, Tang X-L, Duan G-L, Ni X, Zhu X-Y, Liu Y-J, Wang C-N (2016) H2S attenuates LPS-induced acute lung injury by reducing oxidative/nitrative stress and inflammation. Cell Physiol Biochem 40:1603–1612. CrossRefPubMedGoogle Scholar
  24. 24.
    Miura K, Yamanaka S, Ebara T, Okumura M, Imanishi M, Kim S, Nakatani T, Iwao H (2000) Effects of nitric oxide scavenger, carboxy-PTIO on endotoxin-induced alterations in systemic hemodynamics in rats. Jpn J Pharmacol 82:261–264CrossRefGoogle Scholar
  25. 25.
    Yoshida M, Akaike T, Wada Y, Sato K, Ikeda K, Ueda S, Maeda H (1994) Therapeutic effects of imidazolineoxyl N-oxide against endotoxin shock through its direct nitric oxide-scavenging activity. Biochem Biophys Res Commun 202:923–930. CrossRefPubMedGoogle Scholar
  26. 26.
    Marchini T, Magnani ND, Paz ML, Vanasco V, Tasat D, Gonzalez Maglio DH, Alvarez S, Evelson PA (2014) Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to residual oil fly ash. Toxicol Appl Pharmacol 274:274–282. CrossRefPubMedGoogle Scholar
  27. 27.
    Walrand S, Valeix S, Rodriguez C, Ligot P, Chassagne J, Vasson M-P (2003) Flow cytometry study of polymorphonuclear neutrophil oxidative burst: a comparison of three fluorescent probes. Clin Chim Acta 331:103–110. CrossRefPubMedGoogle Scholar
  28. 28.
    Miranda KM, Espey MG, Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5:62–71. CrossRefPubMedGoogle Scholar
  29. 29.
    Buchholz B, D’Annunzio VV, Giani JF, Siachoque N, Dominici FP, Turyn D, Perez V, Donato MM, Gelpi RJ (2014) Ischemic postconditioning reduces infarct size through the alpha1-adrenergic receptor pathway. J Cardiovasc Pharmacol 63:504–511. CrossRefPubMedGoogle Scholar
  30. 30.
    Sutherland FJ, Shattock MJ, Baker KE, Hearse DJ (2003) Mouse isolated perfused heart: characteristics and cautions. Clin Exp Pharmacol Physiol 30:867–878. CrossRefPubMedGoogle Scholar
  31. 31.
    Jain M, Lim CC, Nagata K, Davis VM, Milstone DS, Liao R, Mortensen RM (2001) Targeted inactivation of Galpha(i) does not alter cardiac function or beta-adrenergic sensitivity. Am J Physiol Hear Circ Physiol 280:H569–H575. CrossRefGoogle Scholar
  32. 32.
    Marchini T, D’Annunzio V, Paz ML, Cáceres L, Garcés M, Perez V, Tasat D, Vanasco V, Magnani N, Gonzalez Maglio D, Gelpi RJ, Alvarez S, Evelson P (2015) Selective TNF-α targeting with infliximab attenuates impaired oxygen metabolism and contractile function induced by an acute exposure to air particulate matter. Am J Physiol Heart Circ Physiol 309:H1621–H1628. CrossRefPubMedGoogle Scholar
  33. 33.
    Mela L, Seitz S (1979) Isolation of mitochondria with emphasis on heart mitochondria from small amounts of tissue. Methods Enzym 55:39–46CrossRefGoogle Scholar
  34. 34.
    Cadenas E, Boveris A (1980) Enhancement of hydrogen peroxide formation by protophores and ionophores in antimycin-supplemented mitochondria. Biochem J 188:31–37CrossRefGoogle Scholar
  35. 35.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275. CrossRefGoogle Scholar
  36. 36.
    Boveris A, Costa LE, Cadenas E, Poderoso JJ (1999) Regulation of mitochondrial respiration by adenosine diphosphate, oxygen, and nitric oxide. Methods Enzym 301:188–198CrossRefGoogle Scholar
  37. 37.
    Vives-Bauza C, Yang L, Manfredi G (2007) Assay of mitochondrial ATP synthesis in animal cells and tissues. Methods Cell Biol 80:155–171. CrossRefPubMedGoogle Scholar
  38. 38.
    Marchini T, Magnani N, D’Annunzio V, Tasat D, Gelpi RJ, Alvarez S, Evelson P (2013) Impaired cardiac mitochondrial function and contractile reserve following an acute exposure to environmental particulate matter. Biochim Biophys Acta Gen Subj 1830:2545–2552. CrossRefGoogle Scholar
  39. 39.
    Haines TH, Dencher NA (2002) Cardiolipin: a proton trap for oxidative phosphorylation. FEBS Lett 528:35–39. CrossRefPubMedGoogle Scholar
  40. 40.
    Vanasco V, Magnani ND, Cimolai MC, Valdez LB, Evelson P, Boveris A, Alvarez S (2012) Endotoxemia impairs heart mitochondrial function by decreasing electron transfer, ATP synthesis and ATP content without affecting membrane potential. J Bioenerg Biomembr 44:243–252. CrossRefPubMedGoogle Scholar
  41. 41.
    Yonetani T (1967) Cytochrome oxidase: beef heart. In: Methods in enzymology. pp 332–335. Google Scholar
  42. 42.
    Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ (2003) Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem 278:36027–36031. CrossRefGoogle Scholar
  43. 43.
    Bryan NS, Grisham MB (2007) Methods to detect nitric oxide and its metabolites in biological samples. Free Radic Biol Med 43:645–657. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Antunes F, Cadenas E (2001) Cellular titration of apoptosis with steady state concentrations of H2O2: submicromolar levels of H2O2 induce apoptosis through fenton chemistry independent of the cellular thiol state. Free Radic Biol Med 30:1008–1018. CrossRefPubMedGoogle Scholar
  45. 45.
    Vanasco V, Evelson P, Boveris A, Alvarez S (2010) In situ and real time muscle chemiluminescence determines singlet oxygen involvement in oxidative damage during endotoxemia. Chem Biol Interact 184:313–318. CrossRefPubMedGoogle Scholar
  46. 46.
    Connelly L, Palacios-Callender M, Ameixa C, Moncada S, Hobbs AJ (2001) Biphasic regulation of NF-kappa B activity underlies the pro- and anti-inflammatory actions of nitric oxide. J Immunol 166:3873–3881. CrossRefPubMedGoogle Scholar
  47. 47.
    Walley KR, McDonald TE, Higashimoto Y, Hayashi S (1999) Modulation of proinflammatory cytokines by nitric oxide in murine acute lung injury. Am J Respir Crit Care Med 160:698–704. CrossRefPubMedGoogle Scholar
  48. 48.
    Millar CGM, Thiemermann C (2002) Carboxy-PTIO, a scavenger of nitric oxide, selectively inhibits the increase in medullary perfusion and improves renal function in endotoxemia. Shock 18:64–68CrossRefGoogle Scholar
  49. 49.
    van de Sandt AM, Windler R, Gödecke A, Ohlig J, Zander S, Reinartz M, Graf J, van Faassen EE, Rassaf T, Schrader J, Kelm M, Merx MW (2013) Endothelial NOS (NOS3) impairs myocardial function in developing sepsis. Basic Res Cardiol 108:330. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Ortiz F, García JA, Acuña-Castroviejo D, Doerrier C, López A, Venegas C, Volt H, Luna-Sánchez M, López LC, Escames G (2014) The beneficial effects of melatonin against heart mitochondrial impairment during sepsis: inhibition of iNOS and preservation of nNOS. J Pineal Res 56:71–81. CrossRefPubMedGoogle Scholar
  51. 51.
    Jarkovska D, Markova M, Horak J, Nalos L, Benes J, Al-Obeidallah M, Tuma Z, Sviglerova J, Kuncova J, Matejovic M, Stengl M (2018) Cellular mechanisms of myocardial depression in porcine septic shock. Front Physiol 9:726. CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Kirkeboen KA, Strand OA (1999) The role of nitric oxide in sepsis—an overview. Acta Anaesthesiol Scand 43:275–288CrossRefGoogle Scholar
  53. 53.
    Aird WC (2003) The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 101:3765–3777. CrossRefGoogle Scholar
  54. 54.
    Predonzani A, Cali B, Agnellini AH, Molon B, Calì B, Agnellini AH, Molon B, Cali B, Agnellini AH, Molon B (2015) Spotlights on immunological effects of reactive nitrogen species: when inflammation says nitric oxide. World J Exp Med 5:64–76. CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Cortese-Krott MM, Rodriguez-Mateos A, Sansone R, Kuhnle GGC, Thasian-Sivarajah S, Krenz T, Horn P, Krisp C, Wolters D, Heiß C, Kröncke K-D, Hogg N, Feelisch M, Kelm M (2012) Human red blood cells at work: identification and visualization of erythrocytic eNOS activity in health and disease. Blood 120:4229–4237. CrossRefPubMedGoogle Scholar
  56. 56.
    Kleinbongard P, Schulz R, Rassaf T, Lauer T, Dejam A, Jax T, Kumara I, Gharini P, Kabanova S, Ozüyaman B, Schnürch H-G, Gödecke A, Weber A-A, Robenek M, Robenek H, Bloch W, Rösen P, Kelm M (2006) Red blood cells express a functional endothelial nitric oxide synthase. Blood 107:2943–2951. CrossRefPubMedGoogle Scholar
  57. 57.
    Merx MW, Gorressen S, van de Sandt AM, Cortese-Krott MM, Ohlig J, Stern M, Rassaf T, Gödecke A, Gladwin MT, Kelm M (2014) Depletion of circulating blood NOS3 increases severity of myocardial infarction and left ventricular dysfunction. Basic Res Cardiol 109:398. CrossRefPubMedGoogle Scholar
  58. 58.
    Liao R, Podesser BK, Lim CC (2012) The continuing evolution of the Langendorff and ejecting murine heart: new advances in cardiac phenotyping. Am J Physiol Heart Circ Physiol 303:H156–H167. CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Bell RM, Mocanu MM, Yellon DM (2011) Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion. J Mol Cell Cardiol 50:940–950. CrossRefPubMedGoogle Scholar
  60. 60.
    Paula TD, Silva BR, Grando MD, Souza HCD, Bendhack LM (2018) Activation of TP receptors induces high release of PGI2 in coronary arteries of renal hypertensive rats. J Mol Cell Cardiol 122:125–133. CrossRefPubMedGoogle Scholar
  61. 61.
    Kane GC, Karon BL, Mahoney DW, Redfield MM, Roger VL, Burnett JC, Jacobsen SJ, Rodeheffer RJ (2011) Progression of left ventricular diastolic dysfunction and risk of heart failure. JAMA 306:856–863. CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Avlas O, Fallach R, Shainberg A, Porat E, Hochhauser E (2011) Toll-like receptor 4 stimulation initiates an inflammatory response that decreases cardiomyocyte contractility. Antioxid Redox Signal 15:1895–1909. CrossRefPubMedGoogle Scholar
  63. 63.
    Hill BGG, Dranka BPP, Zou L, Chatham JCC, Darley-Usmar VMM (2009) Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal. Biochem J 424:99–107. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Cimolai MC, Vanasco V, Marchini T, Magnani ND, Evelson P, Alvarez S (2014) Alpha-lipoic acid protects kidney from oxidative stress and mitochondrial dysfunction associated to inflammatory conditions. Food Funct 5:3143–3150. CrossRefPubMedGoogle Scholar
  65. 65.
    Boveris A, Carreras MC, Poderoso JJ (2010) The regulation of cell energetics and mitochondrial signaling by nitric oxide. In: Louise JI (ed) Nitric oxide biology and pathobiology, 2nd edn. pp 441–482. CrossRefGoogle Scholar
  66. 66.
    Valdez LB, Bombicino SS, Iglesias DE, Rukavina Mikusic I, Boveris A (2018) Mitochondrial peroxynitrite generation is mainly driven by superoxide steady-state concentration rather than by nitric oxide steady-state concentration. Int J Mol Biol Open Access 3:56–61. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Tamara Antonela Vico
    • 1
    • 2
  • Timoteo Marchini
    • 1
    • 3
  • Santiago Ginart
    • 4
  • Mario Alejandro Lorenzetti
    • 5
  • Juan Santiago Adán Areán
    • 2
  • Valeria Calabró
    • 1
  • Mariana Garcés
    • 1
    • 3
  • Mariana Cristina Ferrero
    • 6
  • Tamara Mazo
    • 1
    • 7
  • Verónica D’Annunzio
    • 1
    • 7
  • Ricardo J. Gelpi
    • 1
    • 7
  • Daniel Corach
    • 4
  • Pablo Evelson
    • 1
    • 3
  • Virginia Vanasco
    • 1
    • 2
    Email author
  • Silvia Alvarez
    • 1
    • 2
    Email author
  1. 1.Instituto de Bioquímica y Medicina Molecular (IBIMOL), Facultad de Farmacia y BioquímicaUniversidad de Buenos Aires-CONICETBuenos AiresArgentina
  2. 2.Departamento de Química Analítica y Fisicoquímica, Facultad de Farmacia y Bioquímica, Cátedra de FisicoquímicaUniversidad de Buenos AiresBuenos AiresArgentina
  3. 3.Departamento de Química Analítica y Fisicoquímica, Facultad de Farmacia y Bioquímica, Cátedra de Química General e InorgánicaUniversidad de Buenos AiresBuenos AiresArgentina
  4. 4.Servicio de Huellas Digitales Genéticas, Facultad de Farmacia y BioquímicaUniversidad de Buenos AiresBuenos AiresArgentina
  5. 5.División Patología, Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP), CONICET-GCBAHospital de Niños Ricardo GutiérrezBuenos AiresArgentina
  6. 6.Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y BioquímicaUniversidad de Buenos Aires-CONICETBuenos AiresArgentina
  7. 7.Departamento de Patología, Instituto de Fisiopatología Cardiovascular, Facultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

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