Palavras-chave
Atorvastatina
Leucopenia
Caquexia
Agente anticancer
Como Citar
Copyright © | Todos os direitos reservados.
A revista detém os direitos autorais exclusivos de publicação deste artigo nos termos da lei 9610/98.
Reprodução parcial
É livre o uso de partes do texto, figuras e questionário do artigo, sendo obrigatória a citação dos autores e revista.
Reprodução total
É expressamente proibida, devendo ser autorizada pela revista.
Resumo
Objetivo: Estudar a administração da atorvastatina sobre a mucosite oral (MO), avaliando dosagem, estado clínico dos animais, manutenção do número de leucócitos e caquexia em um modelo de MO quimioinduzida pelo quimioterápico 5-Fluorouracil (5-FU). Métodos: Foram utilizados 36 ratos wistar divididos em Grupo Controle (GC): 5-FU + Solução Salina 0,9%; Grupo I (GI): 5-FU + 1mg de atorvastatina; Grupo II (GII): 5-FU + 5mg de atorvastatina e Grupo III (GIII): 5-FU + 10mg de atorvastatina. Resultados: Através das análises histológicas, o GC apresentou perda de epitélio de revestimento; GI manteve a integridade do epitélio de revestimento, porém mais fino; GII apresentou o epitélio de revestimento preservado e Grupo III manteve epitélio de revestimento espesso. Contagem global de leucócitos: GC foi considerada alta; GI com contagem baixa; GII apresentou queda e GIII manteve o leucograma dentro dos valores de normalidade. Após a indução da MO, verificou-se intensa caquexia e perda de peso no GC; GI caquexia menor; Grupos II e III houve caquexia perda de peso, mas melhora mais rápida, com tendência a ganho ponderal. Conclusão: O potencial preventivo da atorvastatina em ratos wistar foi definida a dose de 10mg/kg/dia como preventiva e mais segura.
Referências
ARAÚJO AA. et al. Azilsartan reduced TNF-α and IL-1β levels, increased IL-10 levels and upregulated VEGF, FGF, KGF, and TGF-α in an oral mucositis model. Plos One, 2015; 10(2).
ANDALIB S, et al. In vitro and in vivo delivery of atorvastatin: A comparative study of anti-inflammatory activity of atorvastatin loaded copolymeric micelles. J Biomater Appl, 2018; 32(8): 1127-1138.
AHMED AA, et al. α-Lipoic acid ameliorates oral mucositis and oxidative stress induced by methotrexate in rats. Histological and immunohistochemical study. Life Sci, 2017; 171:51-9.
AZEVEDO IM, et al. Effect of simvastatin in attenuation of mucositis induced by methotrexate in rats. J Surg Clin Res, 2010; 1:22-32.
BARBER C, et al. Comparing pain control and ability to eat and drink with standard therapy vs. Gelclair: a preliminary, double centre, randomized controlled trial on patients with radiotherapy induced oral mucositis. Support Care Cancer, 2007; 15(4):427 40.
CAMPOS MIC, et al. Oral mucositis in cancer treatment: natural history, prevention and treatment (Review). Mol Clin Oncol, 2014; 2(3):337-340.
CAMPOS MIC, et al. Atorvastatin and trans-caryophyllene for the prevention of leukopenia in an experimental chemotherapy model in Wistar rats. Mol Clin Oncol, 2015; 3(4):825-8.
CAMPOS MIC, et al. Induced oral mucositis in Wistar rats treated with different drugs: Preventive potential in cytokine production. Mol Clin Oncol, 2021; 14(6):127.
CINAUSERO CM, et al. New frontiers in the pathobiology and treatment of cancer regimen-related mucosal injury. Front Pharmacol, 2017; 8:354.
CHAVELI-LÓPEZ B, BAGÁN-SEBASTIÁN JV. Treatment of oral mucositis due to chemotherapy. J Clin Exp Dent, 2016; 8(2):201-9.
DODD MJ, et al. Randomized clinical trial of the effectiveness of 3 commonly used mouthwashes to treat chemotherapy induced mucositis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2000; 90(1):39 47.
DÖRR W, et al. Radiation induced changes in cellularity and proliferation in human oral mucosa. Int J Radiat Oncol Biol Phys, 2002; 52(4):911 7.
FERRO D, et al. Sinvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia. J Am Coll Cardiol, 2000; 36(2):427-31.
HITOMI S, et al. [6]-gingerol and [6]-shogaol, active ingredients of the traditional Japanese medicine hangeshashinto, relief oral ulcerative mucositis-induced pain via action on Na(+) channels. Pharmacol Res, 2017; 117:288-302.
KANAGALINGAM J, et al. Patient and oncologist perceptions regarding symptoms and impact on quality-of-life of oral mucositis in cancer treatment: results from the Awareness Drives Oral Mucositis Percep Tion (ADOPT) study. Support Care Cancer, 2018; 26(7):2191-2200.
KIRK J, et al. Text mining-based in silico drug discovery in oral mucositis caused by high-dose cancer therapy. Support Care Cancer, 2018; 26(8):2695-705.
KOWANKO I, et al. The effec¬tiveness of strategies for preventing and treating chemotherapy and radiation induced oral mucositis in patients with cancer. Australia: Joanna Briggs Institute for Evidence Based Nursing and Midwifery, Systemic Review, 1998; 2.
LAUF U, et al. Inhibition of 3-Hydroxy-3-methylglutaryl (HMG) - CoA reductase blocks hypoxia-mediated down-regulation of endothelial nitric oxide synthase. J Biol Chem, 1997; 12, 272(50):31725-9.
LEGOUTÉ F, et al. Low-level laser therapy in treatment of chemoradiotherapy-induced mucositis in head and neck cancer: results of a randomised, triple blind, multicentre phase III trial. Radiat Oncol, 2019; 14(1):83.
MEDEIROS CA, et al. Effect of atorvastatin on 5-fluorouracil experimental oral mucositis. Cancer Chemother Pharmacol, 2011; 67(5):1085-100.
ONSENG K, et al. Beneficial effect of adjuvant melatonin in minimizing oral mucositis complications in head and neck cancer patients receiving concurrent chemoradiation. J Altern Complement Med, 2017; 23(12):957-6.
SOLHEIM S, et al. Seljeflot I, Arnesen H, EIkvar L. Reduced levels of TNF- in hypercholesterolemic individuals after treatment with pravastatin for 8 weeks. Atheroclerosis, 2001; 157(2):411-5.
SONIS ST. An animal model for mucositis induced by cancer chemotherapy. Oral Surgery Oral Med Oral Pathol, 1990; 69(4):437-443.
SONIS ST. Mucositis as a biological process: a new hypothesis for the development of chemotherapy induced stomatotoxicity. Oral Oncol, 1998; 34(1):39 43.
SONIS ST. New thoughts on the initiation of mucositis. Oral Dis, 2010; 16(7):597-600.
SONIS ST, Villa A. Phase II investigational oral drugs for the treatment of radio/chemotherapy induced oral mucositis. Expert Opin Investig Drugs, 2018; 27(2):147-54.
SOFIS MJ, et al. KU32 prevents 5-fluorouracil induced cognitive impairment. Brain Res, 2017; 30:186-190.
SHIMAMURA Y, et al. Takeuchi I, Terada H, Makino K. A mouse model for oral mucositis induced by cancer chemotherapy. Anticancer Res, 2018; 38(1):307-312.
STEINMANN D, et al. Eilers V, Beynenson D, Buhck H, Fink M. Effect of Traumeel Son pain and discomfort in
radiation induced oral mucositis: a preliminary observational study. Altern Ther Health Med, 2012; 18(4):12-8.
VIEIRA WDA, et al. Modelo experimental de Mucosite Oral e intestinal em ratos Wistar. Rev Int Est Exp, 2018; 10:01-60.
WALLADBEGI J, et al. Smith SA, Grayson AK, Murdoch C, Jontell M, Colley HE. Cooling of the oral mucosa to prevent adverse effects of chemotherapeutic agents: An in vitro study. J Oral Pathol Med, 2018; 47(5):477-83.
WHITTAKER AL, et al. Wirthensohn MG. Effects of commercially produced almond by-products on chemotherapy-induced mucositis in rats. J Gastrointest Pathophysiol, 2017; 8(4):176-87.