Nanocapsules With Naringin And Naringenin Affect Hepatic and Renal Energy Metabolism Without Altering Serum Markers of Toxicity in Rats

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Jadriane Fontoura Friedrich
Jessica Tadiello dos Santos
Ariane Ribas Pohl
Vivian Shinobu Kishimoto Nishihira
Morgana Brondani
Jessica Dotto de Lara
Itiane Diehl de Franceschi
Luciane Rosa Feksa
Renata Platcheck Raffin
Rodrigo de Almeida Vaucher
Virginia Cielo Rech

Abstract

Naringin and naringenin are flavonoids found in citrus fruits and have several health benefits, however these compounds are susceptible to degradation, limiting their therapeutic application. To solve this problem, an alternative is to incorporate them into nanocapsules. The aim of this work was to evaluate the toxicity of these nanocapsules against renal and hepatic serum markers and also on the activities of pyruvate kinase, Mg2+-ATPase, and creatine kinase. Nanocapsules containing naringin and naringenin, nanocapsules without the active compounds and the compounds in their free form were administered orally, once a day, for 28 days. After treatment, the serum levels of hepatic and renal markers were not altered, nor the activities of pyruvate kinase tissue, however, the treatment of nanocapsules with flavonoids increased the activities of mitochondrial creatine kinase in the kidney and hepatic Mg2+-ATPase. Thus, renal and hepatic serum markers, which are normally used as indicators of toxicity, did not change after the period of administration of the nanoparticles. However, the activities of important enzymes of the energy metabolism in these organs were affected. Our findings reinforce that nanomaterial testing for toxicity needs to go beyond traditional methods to ensure the safe use of nanoparticles for therapeutic purposes.

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Fontoura Friedrich, J., Tadiello dos Santos, J., Ribas Pohl, A., Shinobu Kishimoto Nishihira, V. ., Brondani, M. ., Dotto de Lara, J. ., Diehl de Franceschi, I., Rosa Feksa, L., Platcheck Raffin, R. ., de Almeida Vaucher, R. ., & Cielo Rech, V. (2020). Nanocapsules With Naringin And Naringenin Affect Hepatic and Renal Energy Metabolism Without Altering Serum Markers of Toxicity in Rats. International Journal for Innovation Education and Research, 8(10), 250-262. https://doi.org/10.31686/ijier.vol8.iss10.2676
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References

AHMED, O. M. et al. Antidiabetic effects of hesperidin and naringin in type 2 diabetic rats. Diabetol Croat, v. 41, n. 2, 2012.

AHMED, O. M. et al. The Preventive Effects and the Mechanisms of Action of Navel Orange Peel Hydroethanolic Extract, Naringin, and Naringenin in N-Acetyl-p-aminophenol-Induced Liver Injury in Wistar Rats. Oxid Med Cell Longev 2019: 1-19.

ALAM, M. A. et al. Effect of Citrus Flavonoids, Naringin and Naringenin, on Metabolic Syndrome and Their Mechanisms of Action12. Adv Nutr 5(4): 404-417, 2014.

AMUDHA, K.; SHAGIRTHA, K. and ELANGOVAN, P. Naringin improves nickel-induced alterations of acetylcholinesterase, adenosine triphosphatases, and oxidative stress in brain of rats. J. Nat. Prod. Biomed. Res 1: 21-28, 2015.

ARUMUGAM, R. et al. Effect of naringin on ammonium chloride-induced hyperammonemic rats: A dose-dependent study. J Acute Med 6(3): 55-60, 2016.

BAAIJ, et al. Magnesium in man: implications for health and disease. Physiol Rev 95(1): 1-46, 2015.

BALDISSERA, M. D. et al. Activity of cholinesterases, pyruvate kinase and

adenosine deaminase in rats experimentally infected by Fasciola hepatica: Influences of these enzymes on inflammatory response and pathological findings. Pathol Res Pract 211 (11): 871-876, 2015.

CHAN, K. M. et al. A direct colorimetric assay for Ca2+-stimulated ATPase activity. Anal Biochem 157(2): 375-380, 1986.

CORDENONSI, L. M. et al. Simultaneous separation and sensitive detection of naringin and naringenin in nanoparticles by chromatographic method indicating stability and photodegradation kinetics. Biomed Chromatogr 30(2): 155-162, 2016.

DE FRANCESCHI, I. D. et al. Effect of Leucine Administration to Female Rats During Pregnancy and Lactation on Oxidative Stress and Enzymes Activities of Phosphoryltransfer Network in Cerebral Cortex and Hippocampus of the Offspring. Neurochem Res 38(3): 632-643, 2013.

DEIGNAN, J. L.; CEDERBAUM, S. D. and GRODY, W. W. Contrasting Features of Urea Cycle Disorders in Human Patients and Knockout Mouse Models. Mol Genet Metab 93(1): 7-14, 2008.

DIAZ GONZALEZ, F. H. AND SCHEFFER, J. L. Perfil sangüíneo: ferramenta de análise clínica, metabólica e nutricional. Simpósio de Patologia Clínica Veterinária, 1, 2003.

FERREIRA, G. L. Role of the phosphocreatine system on energetic homeostasis in skeletal and cardiac muscles. Einstein (Sao Paulo) 12(1): 126-131, 2014.

FERREIRA, C. F. Desenvolvimento, caracterização e avaliação da citotoxicidade de naringina e naringenina nanoencapsuladas. Disciplinarum Scientia 16(2): 285-299, 2015.

FISKE, C. H. and SUBBAROW, Y. The colorimetric determination of phosphorus. J Biol Chem 66(2): 375-400, 1925.

GUYTON, A. C. and HALL, J. E. Tratado de Fisiologia Médica. 11ª ed. Rio de Janeiro, Elsevier Ed, 2006.

HUGHES, B. P. Amethod for the estimation of serumcreatine kinase and its use in comparing creatine kinase and aldolase activity in normal and pathological sera. Clin Chim Acta 7(5), 597-603, 1962.

ISRAELSEN, W. J. and VANDER HEIDEN, M. G. Pyruvate kinase: function, regulation and role in cancer. Semin Cell Dev Biol 43: 43–51, 2015.

KATARIA, A. TRASANDE, L. and TRACHTMAN, H. The effects of environmental chemicals on renal function. Nat Rev Nephrol 11(10): 610, 2015.

KOLLING, J. et al. Resveratrol and resveratrol-hydroxypropyl-β-cyclodextrin complex recovered the changes of creatine kinase and Na+ , K+ -ATPase activities

found in the spleen from streptozotocin-induced diabetic rats. An Acad Bras Cienc. 91(3): 1- 12, 2019.

KRIZ, W. and KAISSLING, B. Structural organization of the mammalian kidney. J Physiol Pathophysiol 3: 587-654, 2008.

LEONG, S. F. et al. Energy‐metabolising enzymes in brain regions of adult and aging rats. J Neurochem 37(6): 1548-1556, 1981.

LI, P. et al. Acute and 13 weeks subchronic toxicological evaluation of naringin in SpragueDawley rats. Food Chem Toxicol 60: 1-9, 2013.

LOWRY, O. H. et al. Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275, 1951.

MOTTA, V. T. Bioquímica clínica para o laboratório: princípios e interpretações. 5. ed. Rio de Janeiro: Medbook, 2009.

MUSSOI, T. D. and RECH ,V. C. Metabolismo energético. In: Rossi & Poltronieri. (Orgs.). Tratado de Nutrição e Dietoterapia, Rio de Janeiro: Guanabara Koogan, 31-50, 2019.

MUSTAFIN, R. I. 2011. Interpolymer combinations of chemically complementary grades of Eudragit copolymers: a new direction in the design of peroral solid dosage forms of drug delivery systems with controlled release. Pharm Chem J 45(5): 285, 2011.

NELSON, D. L. and COX, M. M. 2014. Princípios de bioquímica de Lehninger. Porto Alegre: Artmed. 6. Ed, 2014.

NISHIHIRA, V. S. K. et al. In vitro and in silico protein corona formation evaluation of curcumin and capsaicin loaded-solid lipid nanoparticles. Toxology in Vitro 61: 1-13, 2019.

NOVO, M. S, GERACITANO, L. A. and HENNING, P. The pattern of relationships between nanosciences, health, and biology: a historical survey using Citespace. Hist Cienc Saude Manguinhos 20(4): 1657-1670, 2013.

NOZADZE, E. et al. Molecular mechanism of Mg-ATPase activity. J Membr Biol 248(2): 295-300, 2015.

PAPASANI, V. M. R.; HANUMANTHARAYAPPA, B. and ANNAPURNA, A. Cardioprotective effect of naringin against doxorubicin induced cardiomyopathy in rats. Indo Am j pharm res 4(5): 2593-2598, 2014.

PARI, L. and AMUDHA, K. Hepatoprotective role of naringin on nickelinduced toxicity in male Wistar rats. Eur J Pharmacol 650 (1):364–70, 2011.

PILCHOVA, I. et al. The involvement of Mg2+ in regulation of cellular and mitochondrial functions. Oxid Med Cell Longev, 2017.

POHL, A. R. et al. Effect of nanocapsules with naringin and naringenin on oxidative stress parameters in rats stomach. Disciplinarum Scientia 18(3): 459-471, 2017.

RECH, V. C. et al. Inhibition of creatine kinase activity by cystine in the kidney of young rats. Pediatr Res 60(2): 190, 2006.

RECH, V. C. et al. Cysteamine prevents inhibition of thiol-containing enzymes caused by cystine or cystine dimethylester loading in rat brain cortex. Metab Brain Dis 23(2): 133, 2008.

RECH, V. C. et al. Thiol/disulfide status regulates the activity of thiol-containing kinases related to energy homeostasis in rat kidney. An Acad Bras Cienc 90(1): 99-108, 2017.

ROWE, I. et al. Defective Glucose Metabolism in Polycystic Kidney Disease Identifies A Novel Therapeutic Paradigm. Nat Med 19(4): 488–493, 2013.

SHUCH, B.; LINEHAN, W. M. and SRINIVASAN, R. Aerobic Glycolysis: A Novel Target in Kidney Cancer. Expert Rev Anticancer Ther 13(6): 711–719, 2013.

SILVA, R. F. et al. Relation Between Physical Activity, Oxidative Stress and Magnesium. Nutrição em pauta 15-19, 2013.

SUN, X. et al. Aluminum Chloride Causes the Dysfunction of Testes Through Inhibiting the ATPase Enzyme Activities and Gonadotropin Receptor Expression in Rats. Biol Trace Elem Res 183:296–304, 2018.

WALLIMANN, T. and HEMMER, W. Creatine kinase in non-muscle tissues and cells. Mol Cell Biochem 133-134(1): 193–220, 1994.

YEN, F. L. Naringenin-loaded nanoparticles improve the physicochemical properties and the hepatoprotective effects of naringenin in orally-administered rats with CCl4-induced acute liver failure. Pharm. Res 26(4): 893-902, 2009.

YU, L. 2007. Diretrizes da AMB e Sociedade Brasileira de Nefrologia para insuficiência renal aguda. Sociedade Brasileira de Nefrologia (SBN), 2007.