Potencial antioxidante do extrato de folhas de Carica papaya Linn (Caricaceae) em camundongos com estresse oxidativo induzido por ciclofosfamida
DOI:
https://doi.org/10.15448/1980-6108.2020.1.34702Palavras-chave:
antimutagenicidade, defesa antioxidante, etnobotânica, metabólitos secundários, eritropoieseResumo
OBJETIVOS: O objetivo deste estudo foi investigar os efeitos do extrato bruto de folhas de Carica papaya sobre o estresse oxidativo em camundongos induzidos pela ciclofosfamida, bem como a caracterização do perfil fitoquímico deste extrato.
MÉTODOS: Os camundongos Swiss machos receberam 15 dias de tratamento com o extrato (500 mg kg-1, via gavagem) e injeção intraperitoneal de ciclofosfamida (75 mg kg-1) ou salina (0,9%) no 15º dia. Após 24 h do último tratamento, os animais foram anestesiados para retirada do sangue, sacrificados e retirada dos órgãos para análises (fígado, rim e coração). Nos testes bioquímicos foram determinados: parâmetros hematológicos em sangue, aminotransferases, fosfatase alcalina, dosagens de glicose e colesterol total no plasma, antioxidantes enzimáticos e não enzimáticos e marcador de dano lipídico foram avaliados em diferentes tecidos, além de análises genotóxicas e histopatológicas.
RESULTADOS: No extrato de folhas de Carica papaya foram identificados os flavonoides quercetina-3β-D-glicosídeo e rutina, além de resultados positivos para alcaloides, saponinas e taninos. Este extrato aumentou a atividade das enzimas glutationa-S-transferase e catalase no fígado e diminuiu os níveis de glutationa reduzida nos rins, a concentração do hematócrito, a contagem dos glóbulos vermelhos e a hemoglobina. Promoveu a diminuição das espécies reativas de ácido tiobarbitúrico (TBARS) nos rins, a atividade da enzima
aspartato aminotransferase no plasma e foi antimutagênico no teste do micronúcleo.
CONCLUSÕES: O estudo mostrou que o extrato de Carica papaya foi benéfico contra eventos oxidativos e preveniu danos no DNA. O extrato também mostrou hepatotoxicidade, portanto, a infusão prolongada de folhas de mamão não é aconselhável.
Downloads
Referências
Firuzi O, Miri R, Tavakkoli M, Saso L. Antioxidant therapy: Current status and future prospects. Curr Med Chem. 2011;18:3871-88. https://doi.org/10.2174/092986711803414368.
Valko M, Leibfritz D, Jan Moncol J, Cronin MTD, M. Mazur M, Telser J. Review: free. radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2011;39:44-84. https://doi.org/10.1016/j.biocel.2006.07.001.
Popov D. Protein S-glutathionylation: from current basics to targeted modifications. Arch Physiol Biochem. 2014;12:1-8. https://doi.org/10.3109/13813455.2014.944544.
Poprac P, Jomova K, Simunkova M, Kollar V, Rhodes CJ, Valko M. Review: targeting free radicals in oxidative stress-related human diseases. Trends Pharmacol Sci. 2017;38:592-607. https://doi.org/10.1016/j.tips.2017.04.005.
Kallenberg CG. Pro: Cyclophosphamide in lupus nephritis. Nephrol Dial Transplant. 2016;31:1047-52. https://doi.org/10.1093/ndt/gfw069
Sun Y, Ito S, Nishio N, Tanaka Y, Chen N, Liu L, Isobel KI. Enhancement of the acrolein-induced production of reactive oxygen species and lung injury by Gadd 34. Oxid Med Cell Longev. 2015;2015:170309. https://doi.org/10.1155/2015/170309.
Embrapa. Mamão - O produtor pergunta, a Embrapa responde. 500 perguntas 500 respostas. 2nd ed. Brasília: Embrapa Mandioca e Fruticultura; 2013.
Imaga NOA, Gbenle GO, Okochi VI, Akanbi SO, Edeoghon SO, Oibochie, Kehinde V, Bamiro SB. Antisickling property of Carica papaya leaf extract. Afr J Biochem Res. 2009;3(4):102-06.
Tan SA, Ramos S, Martín MA, Mateos R, Harvey M, Ramanathan S, Najimudin N, Alam M, Bravo L, Goya L. Protective effects of papaya extracts on tert-butyl hydroperoxide mediated oxidative injury to human liver cells (An in-vitro study). Free Rad Antioxid. 2012;2(3):10- 19. https://doi.org/10.1155/2015/170309.
Hasimun P, Suwendar GI, Ernasari. Analgetic Activity of Papaya (Carica papaya L.) leaves extract. Procedia Chem. 2014;13:147-49. https://doi.org/10.1155/2015/170309.
Zunjar V, Dash RP, Jivrajani M, Trivedi B, Nivsarkar M. Antithrombocytopenic activity of carpaine and alkaloidal extract of Carica papaya Linn leaves in busulfan induced thrombocytopenic Wistar rats. J Ethnopharmacol. 2016;181:20-25. https://doi.org/10.1016/j.jep.2016.01.035.
Pandey S, Walpoleb C, Cabota PJ, Shawa PN, Batrab J, Hewavitharana AK. Selective anti-proliferative activities of Carica papaya leaf juice extracts against prostate cancer. Biomed Pharmacother. 2017;89:515-23.
https://doi.org/10.1016/j.biopha.2017.02.050.
Indran M, Mahmood AA, Kuppusamy UR. Protective effect of Carica papaya L. leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats. West Indian Med. 2008;57(4):323-26.
Sá PGS, Guimarães AL, Oliveira AP, Siqueira Filho JA, Fontana AP, Damasceno PKF, Branco CRC, Branco A, Almeida JRG. Fenóis totais, flavonoides totais e atividade antioxidante de selaginella convoluta (arn.) spring (Selaginellaceae). Rev. Ciênc Farm Básica Apl. 2012;33:561-66.
Sousa CMM, Silva HR, Vieira GM, Ayres MCC, Costa CLS, Araújo DS, Cavalcenti, LCD, Barros EDS, Araújo PBM, Brandão MS, Chaves MH. Fenóis totais e atividade antioxidante de cinco plantas medicinais. Quim Nova. 2007;30(2):351-55. https://doi.org/10.1590/S0100-40422007000200021.
Castro MS, Pinheiro CCS, Marinho HA. Screeningfitoquímico e físico-químico dos extratos da CurcumazerumbetRoscoe (Zingiberaceae) do Amazonas para a produção de alimentos terapêuticos. Biota Amazônica. 2017;6-11.
Duan K, Yuan Z, Guo W, Meng Y, Cui Y, Kong D, Zhang L. LC-MS/MS determination and pharmacokinetic study of five flavone components after solvent extraction/acid hydrolysis in rat plasma after oral administration of Verbena officinalis L. extract. J Ethnopharmacol. 2011;135(2):201-08. https://doi.org/10.1016/j.jep.2011.01.002.
Oboh G, Olabiyi AA, Akinyemi AJ. Cyclophosphamide- induced oxidative stress in brain: protective effect of hot short pepper (Capsicum frutescens L. var. abbreviatum). Exp Toxicol Pathol. 2010;62(3):227-33. https://doi.org/10.1016/j.etp.2009.03.011.
Misra HP, Fridovich I. The role of superoxide anion in the auto-oxidation o epinephrine and a simple assay for
superoxide dismutase. J Biol Chem. 1972;247(10):3170-75.
Nelson DP, Kiesow LA. Enthalphy of decomposition of hydrogen peroxide by catalase at 25 °C (with molar extinction coefficients of H2O2 solution in the UV). Anal Biochem. 1972;49(2),474-78. https://doi.org/10.1016/0003-2697(72)90451-4.
Habig WH, Pabst MJ, Jacoby WB. Glutathione S-transferase, the first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249(22):7130-39.
Sedlack J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem. 1968;25:192-205. https://doi.org/10.1016/0003-2697(68)90092-4.
Buege JA, Aust SD. Microsomal lipid peroxidation methods. Enzymol. 1978;52:302-309. https://doi.org/10.1016/S0076-6879(78)52032-6.
Bradford MM. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the
principle of protein-dye binding. Anal Biochem. 1976;72:248-54. https://doi.org/10.1016/0003-2697(76)90527-3.
MacGregor JT, Heddle JA, Hit M, Margolin BH, Ramel C, Salamone MF, Tice RR, Wild D. Guidelines for the conduct of micronucleus assays in mammalian bone marrow erythrocytes. Mutat Res 1987;189(12):103-12. https://doi.org/10.1016/0165-1218(87)90016-4.
Manoharan K, Banerjee MR. β-Carotene reduces sister chromatid exchange induce chemical carcinogens in mouse mammary cells in organ culture. Cell Biol. Int. Rep. 1985;9:783-89. https://doi.org/10.1016/0309-1651(85)90096-7.
Waters MD, Brady AL, Stack HF, Broxkman HE. Antimutagenic profiles for some model compounds. Mutat Res. 1990;238:57-85. https://doi.org/10.1016/0165-1110(90)90039-E.
Pereira BCA. Teste estatístico para comparar proporções em problemas de citogenética. In: Rabello-Gay MN, Rodrigues MAR, Monteleone Neto R, organizadores, Mutagênese, carcinogênese e teratogênese: métodos e critérios de avaliação. Soc Bras Gene. 1991;113-21.
Kapiszewska M, Soltys E, Visioli F, Cierniak A, Zajac G. The protective ability of the Mediterranean plant extracts against the oxidative DNA damage. The role of the radical oxygen species and the polyphenol content. J Physiol Pharmacol. 2005;56:183-97.
Souza M P, Bataglion GA, Silva FM, Almeida RA, Paz WH, Nobre TA, Marinho JV, Salvador MJ, Fidelis CH, Acho LD, Souza AD, Nunomura RC, Eberlin M N, Lima E S, Koolen HH. Phenolic and aroma compositions of pitomba fruit (Talisia esculenta Radlk.) assessed by LC-MS/ MS and HS-SPME/GC-MS. Food Res Int. 2016;83:87-94. https://doi.org/10.1016/j.foodres.2016.01.031.
Zhou J, Qi Y, Ritho J, Zhang Y, Zheng X, Wu L, Li Y, Sun L. Flavonoid glycosides as floral origin markers to discriminate of unifloral bee pollen by LC-MS/MS. Food Control. 2015;57:54-61. https://doi.org/10.1016/j.foodcont.2015.03.035.
Simirgiotis M J, Quispe C, Areche C, Sepúlveda B. Phenolic compounds in Chilean Mistletoe (Quintral, Tristerixtetrandus) analyzed by UHPLC-Q/Orbitrap/MS/MS and its antioxidant properties. Molecules. 2016;21(3):245. https://doi.org/10.3390/molecules21030245.
Pandit A, Sachdeva T, Bafna P. Ameliorative effect of leaves of Carica papaya in ethanol and antitubercular drug induced hepatotoxicity. Br J Pharmacol. 2013;3(4):648-661. https://doi.org/10.9734/BJPR/2013/4517.
Jnaneshwaria S, Hemshekhara M, Santhosha M S, Sunithaa K, Thusharaa R, Thirunavukkarasub C, Kemparajua K, Girish K S. Crocin, a dietary colorant mitigates cyclophosphamide-induced organ toxicity by modulating antioxidant status and inflammatory cytokines. J Pharm Pharmacol. 2013;65(4):604-14. https://doi.org/10.1111/jphp.12016.
Yu Q, Nie SP, Wang JQ, Liu XZ, Yin PF, Huang DF, Li WJ, Gong DM, Xie MY. Chemoprotective effects of Ganoderma atrum polysaccharide in cyclophosphamide- induced mice. Int J Biol Macromol. 2014;64:395-401. https://doi.org/10.1016/j.ijbiomac.2013.12.029.
Abraham P, Isaac B. The effects of oral glutamine on cyclophosphamide-induced nephrotoxicity in rats. Hum Exp Toxicol. 2011;30(7):616-23. https://doi.org/10.1177/0960327110376552.
Zarei M, Shivanandappa T. Amelioration of cyclophosphamide- induced hepatotoxicity by the root extract of Decalepishamiltonii in mice. Food Chem Toxicol. 2013;57:179-84. https://doi.org/10.1016/j.fct.2013.03.028.
Avci H, Epikmen ET, Ipek E, Tunca R, Birincioglu SS, Aksit H, Sekkin S, Akkoç AN, Boyacioglu M. Protective effects of silymarin and curcumin on cyclophosphamide-induced cardiotoxicity. Exp Toxicol Pathol. 2017;69(5):317-27. https://doi.org/10.1016/j.etp.2017.02.002.
Mansour HH, El kiki SM, Hasan HF. Protective effect of N-acetylcysteine on cyclophosphamide-induced cardiotoxicity in rats. Environ Toxicol Pharmacol. 2015;40(2):417-22. https://doi.org/10.1016/j.etap.2015.07.013.
Hang JH. Modification and inactivation of Cu,Zn-superoxide dismutase by the lipid peroxidation product acrolein. BMB Rep. 2013;46(11):555-60. https://doi.org/10.5483/BMBRep.2013.46.11.138.
Moghe A, Ghare S, Lamoreau B, Mohammad M, Barve S, McClain C, Joshi-Barve S. Molecular mechanisms of acrolein toxicity: Relevance to human disease. Toxicol Sci. 2015;143:242-55. https://doi.org/10.1093/toxsci/kfu233.
Guizani N, Waly M, Ali A, Al-Saidi G, Singh V, Bhatt N, Rahman M S. Papaya epicarp extract protects against hydrogen peroxide-induced oxidative stress in human SH-SY5Y neuronal cells. Exp Biol Med. 2011;236(10):1205-10. https://doi.org/10.1258/ebm.2011.011031.
Oboh G, Olabiyi AA, Akinyemi AJ. Inhibitory effect of aqueous extract of different parts of unripe pawpaw (Carica papaya) fruit on Fe2+ induced oxidative stress in rat pancreas in vitro. Pharm Biol. 2013;51(9):1165-74. https://doi.org/10.3109/13880209.2013.782321.
Sadek MK. Antioxidant and immunostimulant effect of Carica papaya Linn aqueous extract in acrylamide intoxicated rats. Acta Infor Med. 2012;20(3):180-185. https://doi.org/10.5455/aim.2012.20.180-185.
Fahmy SR, Amien A I, Abd-Elgleel FM, Elaskalany SM. Antihepatotoxic efficacy of Mangifera indica L. polysaccharides against cyclophosphamide in rats. Chem Biol Interact. 2016;244(25):113-20. https://doi.org/10.1016/j.cbi.2015.11.009.
Mazzeti AP, Fiorile MC, Primavera A, Lo Bello M. Review: Glutathione transferases and neurodegenerative diseases. Neurochem Int. 2015;82:10-8. https://doi.org/10.1016/j.neuint.2015.01.008.
Nakamura Y, Morimitsu Y, Uzua T, Ohigashi H, Murakami A, Naito Y, Nakagawa Y, Osawa T, Uchida K. A glutathione S-transferase inducer from papaya: rapid screening, identification and structure-activity relationship of isothiocyanates. Cancer Lett. 2000;157(2):193-200. https://doi.org/10.1016/S0304-3835(00)00487-0.
Huang J, Wang S, Zhu M, Chen J, Zhu X. Effects of Genistein, Apigenin, Quercetin, Rutin and Astilbin on serum uric acid levels and xanthine oxidase activities in normal and hyperuricemic mice. Food Chem Toxicol. 2011;49:1943-47. https://doi.org/10.1016/j.fct.2011.04.029.
Shanmugam S, Thangaraj P, Lima BS, Chandran R, Souza de Araújo AA, Narain N, Serafini MR, Júnior LJQ. Effects of luteolin and quercetin 3-β-D-Glucoside identified from Passiflora subpeltata leaves against acetaminophen induced hepatotoxicity in rats. Biomed Pharmacother 2016;83:1278-85. https://doi.org/10.1016/j.biopha.2016.08.044.
Caglayan C, Kandemir FM, Darendelioğlu E, Yıldırım S, Kucukler S, Dortbudak MB. Rutin ameliorates mercuric chloride-induced hepatotoxicity in rats viainterfering with oxidative stress, inflammation and apoptosis. J Trace Elements Med Biol. 2019;56:60-8. https://doi.org/10.1016/j.jtemb.2019.07.011.
Khan JA, Shahdad S, Makhdoomi MA, Hamid S, Bhat GM, Jan Y, Nazir S, Bashir Z, Banoo S. Effect of cyclophosphamide on the microanatomy of liver of albino rats. Int. J Res Med Sci. 2014;2(4):1466-69. https://doi.org/10.5455/2320-6012.ijrms20141141.
Gong P, Chen F X, Wang L, Wang J, Jin S, Ma Y M. Protective effects of blueberries (Vaccinium corymbosumL.) extract against cadmium-induced hepatotoxicity in mice. Environ Toxicol Pharmacol. 2014;37(3):1015-27. https://doi.org/10.1016/j.etap.2014.03.017.
Basu A, Bhattacharjee, A, Samanta A, Bhattacharya S. Prevention of cyclophosphamide-induced hepatotoxicity
and genotoxicity: Effect of an cysteine based oxovanadium (IV) complex on oxidative stress and DNA damage. Environ Toxicol Pharmacol. 2015;40(3):747-57. https://doi.org/10.1016/j.etap.2015.08.035.
Bhatt L, Sebastian B, Joshi V. Mangiferin protects rat myocardial tissue against cyclophosphamide induced cardiotoxicity. J. Ayurveda Integr. Med. 2017;8(2):62-67. https://doi.org/10.1016/j.jaim.2017.04.006.
Nafees S, Rashid S, Ali N, Hasan SK, Sultana S. Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: Role of NFjB/ MAPK pathway. Chem Biol Interact. 2015;231(25):98-107. https://doi.org/10.1016/j.cbi.2015.02.021.
Mohamed MR, Emam MA, Hassan NS, Mogadem AI. Umbelliferone and daphnetin ameliorate carbon tetrachloride-induced hepatotoxicity in rats via nuclear factor erythroid 2-related factor 2-mediated heme oxygenase-1 expression.Environ Toxicol Pharmacol. 2014;38(2):531-41. https://doi.org/10.1016/j.etap.2014.08.004.
Sheikh N, Younas N, Akhtar T. Effect of Carica papaya leaf formulation on Hematology and Serology of normal rat. Biol Pakistan. 2014;60(1):139-42.
Li N, Xia Q, Ruan J, Fu PP, Lin G. Hepatotoxicity and Tumorigenicity Induced by Metabolic. Activation
of Pyrrolizidine Alkaloids in Herbs. Current Drug Metabolism. 2011;12(9):823-34. https://doi.org/10.2174/138920011797470119.
Zunjar V, Mammen D, Trivedi B M, Daniel M. 2011. Pharmacognostic, Physicochemical and Phytochemical Studies on Carica papaya Linn. Leaves. Pharmacog J. 2011;20(3):5-8. https://doi.org/10.5530/pj.2011.20.2.
Ismail Z, Halim S Z, Abdullah NR, Afzan A, Rashid BAA, Jantan I. Safety Evaluation of Oral Toxicity of Carica papaya Linn. Leaves: A Subchronic Toxicity Study in Sprague Dawley Rats. Evid Based Complement Altern Med. 2014;e741470. https://doi.org/10.1155/2014/741470.
Kufe DW, Pollock RD, Weichselbaum RR, Bast RC, Gansler TS, Holland JF, Frei E, editors. Holland-Frei Cancer Medicine. 6th ed. New York: BC Decker; 2003.
Molyneux G, Andrews M, Sones W, York M, Barnett A, Quirk E, Yeung W, Turton J. Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration. Cell Biol Toxicol. 2011;27(1):13-40. https://doi.org/10.1007/s10565-010-9167-1.
Li W, Zhao Y, Li X. Effect of Zishenshengxue capsule on myelosuppression in mice induced by Cyclophosphamide. J Trad Chinese Med. 2013;33(2) (2013):233-237. https://doi.org/10.1016/S0254-6272(13)60131-4.
Song Y, Zhang C, Wang C, Zhao L, Wang Z, Dai Z, Lin S, Kang H, Xiaobin M. Ferulic acid against cyclophosphamide-induced heart toxicity in mice by inhibiting NF-KB Pathway. Evid Based Complement Alternat Med. 2016;e1261270. https://doi.org/10.1155/2016/1261270.
Ahmad N, Fazal H, Ayaz M, Abbasil BH, Mohammad I, Fazal L. Dengue fever treatment with Carica papaya leaves extracts. Asian Pac J Trop Biomed. 2011;330-33. https://doi.org/10.1016/S2221-1691(11)60055-5.
Dharmarathna LC, Wickramasinghe S, Waduge RN, Rajapakse PV, kularatne SA. Does Carica papaya leaf-extract increase the platelet count? An experimental study in a murine model. Asian Pac J Trop Biomed. 2013;3(9):720-24. https://doi.org/10.1016/S2221-1691(13)60145-8.
Tham CS, Chakravarthi S, Haleagrahara N, Alwis R. Morphological study of bone marrow to assess the effects of lead acetate on hemapoiesis and aplasia and the ameliorating role of Carica papaya extract. Exp Ther Med.
;5(2):648-52. https://doi.org/10.3892/etm.2012.851.
Han X, Xue X, Zhao Y, Li Y, Liu W, Zhang J, Fan S. Rutin-enriched extract from Coriandrum sativum L. ameliorates
ionizing radiation-induced hematopoietic injury. Int J Mol Sci. 2017;18(5):942. https://doi.org/10.3390/ijms18050942.
Kour J, Alia MN, Ganaiea HA, Tabassum N. Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic extract of Equisetum arvense. Toxicol Rep. 2017;4:226-33. https://doi.org/10.1016/j.toxrep.2017.05.001.
Lin S, Hao G, Longa M, Laia F, Lia Q, Xionga Y, Tiana Y, Laia D. Oyster (Ostrea plicatulaGmelin) polysaccharides intervention ameliorates cyclophosphamide—Induced genotoxicity and hepatotoxicity in mice via the Nrf2—ARE pathway Shuting. Biomed Pharmacother. 2017;95:1067-71. https://doi.org/10.1016/j.biopha.2017.08.058.
Shruthi S, Vijayalaxmi KK. Antigenotoxic effects of a polyherbal drug septilin against thegenotoxicity of cyclophosphamide in mice. Toxicol Rep. 2016;e563571. https://doi.org/10.1016/j.toxrep.2016.07.001.
Gamal-Eldeen AM, Abo-Zeidb MAM, Ahmed EF. Anti-genotoxic effect of the Sargassum dentifolium extracts: Prevention of chromosomal aberrations, micronuclei, and DNA fragmentation. Exp Toxicol Pathol. 2013;65:27-34. https://doi.org/10.1016/j.etp.2011.05.005.
Ojo OA, Ojo AB, Awoyinka O, Ajiboye BO, Oyinloye BE, Osukoya OA, Olayide II, Ibitayo A. Aqueous extract of Carica papaya Linn roots potentially attenuates arsenic induced biochemical and genotoxic effects in Wistar rats. J Tradit Complement Med. 2018;8(2):324-34. https://doi.org/10.1016/j.jtcme.2017.08.001.
Webster RP, Gawde MD, Bhattacharya RK. Protective effect of rutin, a flavonol glycoside, on the carcinogen induced DNA damage and repair enzymes in rats. Cancer Lett. 1996;109:185-91. https://doi.org/10.1016/S0304-3835(96)04443-6.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2020 Scientia Medica
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Direitos Autorais
A submissão de originais para a Scientia Medica implica na transferência, pelos autores, dos direitos de publicação. Os direitos autorais para os artigos publicados nesta revista são do autor, com direitos da revista sobre a primeira publicação. Os autores somente poderão utilizar os mesmos resultados em outras publicações indicando claramente a Scientia Medica como o meio da publicação original.
Licença Creative Commons
Exceto onde especificado diferentemente, aplicam-se à matéria publicada neste periódico os termos de uma licença Creative Commons Atribuição 4.0 Internacional, que permite o uso irrestrito, a distribuição e a reprodução em qualquer meio desde que a publicação original seja corretamente citada.
