Efeitos da Curcuma longa em animais sadios submetidos a quimioterapia/ Effects of Curcuma longa on healthy animals undergoing chemotherapy
DOI:
https://doi.org/10.34117/bjdv5n12-183Keywords:
Açafrão. Câncer. Oncologia. Fitoterapia. Plantas Medicinais. Docetaxel.Abstract
A Curcuma longa é uma planta originada do sudeste da Ásia, e dentre suas variadas aplicações, tem potencial quimiopreventivo. Este trabalho trata-se de um estudo pré-clínico, que visa avaliar os efeitos da curcuma em animais sadios submetidos a quimioterapia com docetaxel. Foram divididos 8 grupos de ratos Wistar machos para receber curcuma em três diferentes doses (25, 50 e 500mg), combinadas ou não com o quimioterápico, e veículo. Foram coletadas amostras sanguíneas e realizadas análises hematológicas e bioquímicas. Como resultados, encontrou-se níveis reduzidos de ureia com o uso combinado de docetaxel e curcuma nas três estudadas. No entanto, não foi observado alterações nos níveis de creatinina, sódio e potássio entre os grupos de animais. Na análise da função hepática, notou-se uma queda estatisticamente significativa nas transaminases com a associação de docetaxel e curcuma nas doses de 250 mg/Kg e 500 mg/Kg. Já em relação a função pancreática, houve decréscimo nos valores de amilase no grupo do quimioterápico e curcuma 500 mg/Kg, enquanto não foi evidenciado alterações nos índices glicêmicos. Por fim, na avaliação hematológica, houve queda na contagem de plaquetas com o uso do docetaxel com a curcuma 250 mg/Kg e também foi notada redução no número de leucócitos dentre os grupos que receberam o quimioterápico e curcuma nas três doses analisadas. Para as demais células de defesa, os eosinófilos, monócitos, neutrófilos e linfócitos, não houve divergências estatisticamente significativa entre os grupos investigados.Como conclusão, foi demonstrado que a curcuma tem potencial para proteção renal e hepática, estimulante do sistema imune, reparação da função pancreática, potencial prevenção contra o tromboembolismo, consistindo em um importante composto adjuvante ao tratamento oncológico.
References
ABAL, M.; ANDREU J. M.; BARASOAIN, I. Taxanes: microtubule and centrosome targets, and cell cycle dependente mechanisms of action. Curr Cancer Drug Targets, v. 3, n. 3, p. 193-203, 2003.
ABE, R.; OHTANI, K. An ethnobotanical study of medicinal plants and traditional therapies on Batan Island, the Philippines. Journal of Ethnopharmacology, v. 145, p. 554–565, 2013.
ABU-TAWEEL, G. M. Effects of curcumin on the social behavior, blood composition, reproductive hormones in plasma and brain acetylcholinesterase in cadmium intoxicated mice. Saudi Journal of Biological Sciences, v. 23, n. 2, p. 219-228, 2016.
ALI, B. H. et al. Curcumin ameliorates kidney function and oxidative stress in experimental chronic kidney disease. Basic Clin Pharmacol Toxicol,v. 122, n. 1, p. 65-73, 2018.
ARAFA, H. M. M. Uroprotective Effects of Curcumin in Cyclophosphamide-Induced Haemorrhagic Cystitis Paradigm. Nordic Pharmacological Society. Basic & Clinical Pharmacology & Toxicology, v. 104, p. 393–399, 2009.
ARSHAMI, J. et al. Hypolipidemic and antioxidative effects of curcumin on blood parameters, humoral immunity, and jejunum histology in Hy-line hens. Avicenna J Phytomed, v. 3, n. 2, p. 178-85, 2013.
BOSKABADY, M. H.; SHAKERI, F. Anti-inflammatory, antioxidant and immunomodulatory effects of curcumin in sensitized rat. European Respiratory Journal, v. 50, p. 1052, 2017.
CARNERO, A. et al. The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets, v. 8, p. 187–198, 2008.
CHAKRABORTY, B.; SENGUPTA, M. Boosting of nonspecific host response by aromatic spices turmeric and ginger in immunocompromised mice. Cell Immunol, v, 280, n. 1, p. 92-100, 2012.
CHAN, E. W. C. et al. Effects of different drying methods on the antioxidant properties of leaves and tea of ginger species. Food Chemistry, v. 113, n. 1, p. 166–172, 2009.
CHANG, C. J. et al. Beneficial impact of Zingiber zerumbet on insulin sensitivity in fructose-fed rats. Planta Med, v. 78, n. 4, p. 317-25, 2012.
CHAUHAN, D. P. Chemotherapeutic potential of curcumin for colorectal cancer. Curr Pharm Des, v. 8, n. 19, p. 1695-706, 2002.
CHIBA, T. et al. Escalating dose and pharmacokinetic study of nanoparticles curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers. Cancer Chemother Pharmacol, v.69 n. p. 65-70, 2012.
CLARKE, S. J.; RIVORY, L. P. Clinical pharmacokinetics of docetaxel. Clin Pharmacokinet, v. 36, n. 2, p. 99-114, 1999.
DE ALMEIDA, L. P.. Caracterização de pigmentos da C. longa L., avaliação da atividade antimicrobiana e morfogênese in vitro na produção de pigmentos curcuminóides e óleos essenciais. Faculdade de Farmácia, UFMG (Tese de Doutorado). 2006. pp. 120
DESHPANDE, S. S. et al. Subchronic oral toxicity of tumeric and ethanolic tumeric extract in female mice and rats. Toxicol Lett, v. 95, p. 183–193, 1998.
DHILLON, N. et al.. Phase II Trial of Curcumin in Patients with Advanced Pancreatic Cancer. Cancer Therapy: Clinical, v. 14, n. 14, p. 4491-9, 2008.
DI PIERRO, F. et al. Comparative evaluation of the pain-relieving properties of a lecithinized formulation of curcumin (Meriva®), nimesulide, and acetaminophen. Journal of Pain Research, v. 6, n. 3 p. 201-105, 2013.
Farmacopeia Brasileira. Monografia Cúrcuma. Brasília, V edição. 2010. p. 893-897.
FARZAEI, M. H. et al. Curcumin in Liver Diseases: A Systematic Review of the Cellular Mechanisms of Oxidative Stress and Clinical Perspective. Nutrients, v. 10, n. 7, pii. E855, 2018.
FERRI, C. et al. Effectiveness of curcum for trating cancer during chemotherapy. Alternative and Complementary Therapies, v. 24, n. 1, 2018.
FIGUEIREDO, E.; MONTEIRO, M.; FERREIRA, A. Tratado de Oncologia. Rio de Janeiro: Revinter, 2013.
GAO, X. et al. Immunomodulatory activity of curcumin: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro. Biochem Pharmacol, v. 68, n. 1, p. 51-61, 2004.
GHOSH, S. S.; GEHR, T. Q.; GHOSH, S. Curcumin and chronic kidney disease (CKD): major mode of action through stimulating endogenous intestinal alcaline phosphatase. Molecules, v. 19, n. 12, p. 20139-56, 2014.
GOVINDARAJAN, V. S. Turmeric: chemistry, technology and quality. Critical Review Food Science Nutrition, v. 12, n. 3, p. 199-301, 1980.
GRONBERG, H. Prostate cancer epidemiology. Lancet, v. 361, p. 859–864, 2003.
HALLIWELL, B. GUTTERIDGE, J.M.C. Cellular responses to oxidative stress: adaptation, damage, repair, senescence and death. Free Radicals in Biology and Medicine, p.187-267, 2007.
HARRIS, L. E.; ASPLUND, J. M.; CRAMPTON, E. W. An international fed nomenclature and methods for summarizing and using fed data to calculate diets. Utah Agricultural Experiment Station Bulletin, n. 479, p. 47-53, 1968.
JURENKA, J. S. Anti-inflammatory properties of curcumin, a major constituent of C. longa: a review of preclinical and clinical research. Advances in pharmacological Science, v.14, n.2, p.141-53, 2009.
KUNNUMAKKARA, A. B.; ANAND, P.; AGGARWAL, B. B. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett, v. 269, p. 199–225, 2008.
KYUNG, E. J. et al. Evaluation of Hepatoprotective Effect of Curcumin on Liver Cirrhosis Using a Combination of Biochemical Analysis and Magnetic Resonance-Based Electrical Conductivity Imaging. Mediators of Inflammation, v. 2018, p. 1-9, 2018.
LEE, H. Antiplatelet property of Curcuma longa L. rhizome?derived ar?turmerone. Bioresour Technol, v. 97, n. 12, p. 1372–1376, 2006.
MAUREEN, J. et al. Neutrophil Recovery in Breast Cancer Patients Receiving Docetaxel-Containing Chemotherapy with and without Granulocyte Colony-Stimulating Factor Prophylaxis. Oncology, v. 93, p. 323–328, 2017.
NAJAFIAN, M. The effects of curcumin on alpha amylase in diabetics rats. Zahedan Journal of Research in Medical Sciences, v. 17, n. 12, 2015.
OMS. Organização Mundial da Saúde. [Internet]. WHO Monographs on Selected Medicinal Plants - Volume 1. Rhizoma Curcumae Longae. 1999. [acesso em 6 de junho de 2017]. Disponível em:
http://apps.who.int/medicinedocs/es/d/Js2200e/14.html#Js2200e.14
PACHALY, et al. Terapêutica por Extrapolação Alométrica. In: CUBAS, Z.S.; SILVA, J.C.R. & CATÃO-DIAS, J.L. (Org.). Tratado de Animais Selvagens – Medicina Veterinária. 1 ed. São Paulo: Roca, p. 1215-1223, 2006.
PARKIN, D. M. et al. Global cancer statistics, 2002. CA Cancer J Clin, v. 55, p. 74–108, 2005.
SCARTEZZINI P.; SPERONI E. Review on some plants of indian traditional medicinal medicine with antioxidant. Journal of Ethnopharmacology, v. 17, p. 23-43, 2000.
SCHULZ, W. A.; BURCHARDT, M.; CRONAUER, M. V. Molecular biology of prostate cancer. Mol Hum Reprod, v. 9, p. 437–448, 2003.
SCIBERRAS, J. N. et al. The effect of turmeric (Curcumin) supplementation on cytokine and inflammatory marker responses following 2 hours of endurance. Journal of the International Society of Sports Nutrition, Woodland Park, v. 12, n. 1, p. 1-10, 2015.
SETHI, G. et al. The Multifaceted Role of Curcumin in Cancer Prevention and Treatment. Molecules, v.20, n. 2, p. 2728-2729, 2015.
SHARMA, K. K. et al. Traditional use of medicinal plants for anti-ringworm therapy in some parts of Kamrup District of Assam, a North Eastern State of India. Asian Pacific Journal of Tropical Disease, v. 2 Suppl 1, p. S316-319, 2012.
SHARMA, R. A. et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clinical Cancer Research, v.10, n. 20, p. 6847–6854, 2004.
SINGH, R. P.; AGGARWAL R.. Mechanisms of action of novel agents for prostate cancer chemoprevention. Endocr Relat Cancer, v. 13, p. 751–778, 2006.
SKRZYPCZAK-JANKUN, E. et al. Structure of curcumin in complex with lipoxygenase and its significance in cancer. Int J Mol Med, v. 12, n. 1, p. 17-24, 2003.
SRIVASTAVA, K.; BORDIA, A.; VERMA, S. Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins Leukot Essent Fatty Acids, v. 52, n. 4, p. 223–227, 1995.
STEELMAN, L. S. et al. Akt as a therapeutic target in cancer. Expert Opin Ther Targets, v. 12, p. 1139–1165, 2008.
STEVENS, L. A. et al. Assessing kidney function-measured and estimated glomerular filtration rate. N Engl J Med, v. 354, p. 2473-83, 2006.
SURH, Y. J..; NA, H. K. NF-kappaB and Nrf2 as prime molecular targets for chemoprevention and cytoprotection with anti-inflammatory and antioxidant phytochemicals. Genes Nutr, v. 2, p. 313–317, 2008.
TUSHAR, B. S.; SARMA, G. C.; RANGAN, L. Ethnomedical uses of Zingiberaceous plants of Northeast India. Journal of Ethnopharmacology, v. 132, p. 286–296, 2010.
VILELA, C. A. A.; ARTUR, P. O. Drying of C. longa L. in different shapes. Ciencia e Tecnologia de Alimentos, v. 28, n. 2 ,p. 387-394, 2008.
YU, H.; HUANG, Q. Improving the oral bioavailability of curcumin using novel organogel-based nanoemulsions. J Agric Food Chem, v. 60, n. 21, p. 5373-9, 2012.
ZHOU, H.; BEEVERS, C. S.; HUANG, S. The targets of curcumin. Current Drug Targets, v.12, n.3, p.332-347, 2011

