1. Universidade Federal da Bahia
  2. Instituto Multidisciplinar em Saúde (IMS)
  3. Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas (PMPGCF)
  4. Dissertação (PMPGCF)
Use este identificador para citar ou linkar para este item: https://repositorio.ufba.br/handle/ri/39149
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Campo DCValorIdioma
dc.creatorMalheiro, Lara Fabiana Luz-
dc.date.accessioned2024-03-05T14:46:13Z-
dc.date.available2024-03-05T14:46:13Z-
dc.date.issued2024-02-21-
dc.identifier.urihttps://repositorio.ufba.br/handle/ri/39149-
dc.description.abstractCisplatin (CP) is a chemotherapy agent widely used to treat various types of solid tumors. However, its lack of selectivity affects healthy cells, causing several cytotoxic effects, including hepatotoxicity. Although the underlying mechanisms of hepatotoxicity are not fully understood, evidence suggests a significant involvement of the inflammatory process in the exacerbation and progression of tissue damage. Recently, some studies have reported the hepatoprotective effects mediated by regular aerobic physical exercise. However, it is still unclear which intensity is most effective in enhancing these protective effects, especially in acute liver injuries. Therefore, this study aims to compare the impacts between preconditioning with high-intensity interval training (HIIT) and traditional continuous training of light (LIT) and moderate (MIT) intensities on inflammatory markers in Wistar rats with CP-induced hepatotoxicity. For this purpose, 35 Wistar female rats were divided into five groups (n=7 in each group): control and sedentary (C+S); treated with CP and sedentary (CP+S); treated with CP and subjected to LIT (CP+LIT); treated with CP and subjected to MIT (CP+MIT); and treated with CP and subjected to HIIT (CP+HIIT). The training protocols consisted of treadmill running, 5 days a week, for 8 weeks before the CP treatment. At the end of the 8-week training period, the rats received a single injection of CP (5 mg/kg i.p) or saline, and 7 days after the injection, they were euthanized. Liver samples were collected to evaluate the expression of nuclear factor kappa B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1α, IL-1β, IL-6, IL-8, and IL-10, the number of ED-1 positive cells, and M1 (iNOS) and M2 (arginase 1) macrophages markers in the hepatic tissue. Our results show that CP treatment promoted na increase in all pro-inflammatory markers, including TLR4/ NF-κB, pro-inflammatory cytokines, immunostaining of ED-1 positive cells, and expressions of M1 macrophage marker compared to the control group. However, HIIT was the most effective exercise protocol in reducing the increase in all these markes compared to LIT and MIT protocols. Additionally, preconditioning with HIIT potentiated the anti-inflammatory cytokine IL-10 and the M2 macrophage marker expressions, while reducing the expression of the M1 macrophage marker in liver. Thus, the present study suggests that physical preconditioning with HIIT was more effective in promoting hepatoprotective effects than LIT and MIT preconditioning protocols, regulating important inflammatory markers through modulation of the TLR4/NF-κB signaling pathway.pt_BR
dc.description.sponsorshipCNPqpt_BR
dc.description.sponsorshipFapesbpt_BR
dc.languageporpt_BR
dc.publisherUniversidade Federal da Bahia/Campus Anísio Teixeirapt_BR
dc.subjectHepatotoxicidade.pt_BR
dc.subjectCisplatinapt_BR
dc.subjectExercício Fisicopt_BR
dc.subjectHIITpt_BR
dc.subjectInflamaçãopt_BR
dc.subject.otherHepatotoxicitypt_BR
dc.subject.otherCisplatinpt_BR
dc.subject.otherPhysical exercisept_BR
dc.subject.otherHIITpt_BR
dc.subject.otherInflammationpt_BR
dc.titleTreinamento intervalado de alta intensidade atenua a inflamação hepática através da via de sinalização TLR4/NF-kB em ratas com hepatotoxicidade induzida por cisplatinapt_BR
dc.typeDissertaçãopt_BR
dc.publisher.programPrograma Multicêntrico de Pós-Graduação em Ciências Fisiológicas (PMPGCF) pt_BR
dc.publisher.initialsUFBA/CATpt_BR
dc.publisher.countryBrasilpt_BR
dc.subject.cnpqCNPq Ciências Biológicaspt_BR
dc.contributor.advisor1Amaral, Liliany Souza de Brito-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/7005117412401272pt_BR
dc.contributor.referee1Amaral, Liliany Souza de Brito-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/7005117412401272pt_BR
dc.contributor.referee2Gusmão, Amélia Cristina Mendes de Magalhães-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/6313221703674661pt_BR
dc.contributor.referee3Coqueiro, Raildo da Silva-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/1515934360117525pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/8252073883331582pt_BR
dc.description.resumoA cisplatina (CP) é um quimioterápico amplamente utilizado para o tratamento de vários tipos de tumores sólidos, contudo a falta de seletividade afeta células saudáveis, provocando diversos efeitos citotóxicos, incluindo a hepatotoxicidade. Embora os mecanismos envolvidos na hepatotoxicidade não estejam totalmente esclarecidos, evidências apontam para uma importante participação do processo inflamatório no agravamento e progressão dos danos teciduais. Recentemente, alguns estudos têm reportado os efeitos hepatoprotetores da prática regular de exercícios físicos aeróbicos, contudo ainda não está clara a influência da manipulação de suas variáveis sobre tal hepatoproteção, especialmente em lesões hepáticas agudas. Assim, este estudo tem como objetivo comparar os efeitos entre o pré-condicionamento com o treinamento intervalado de alta intensidade (HIIT) e treinamentos tradicionais contínuos de leve (LIT) e moderada (MIT) intensidades sobre marcadores inflamatórios em ratas wistar com hepatotoxicidade induzida por CP. Para tanto, 35 ratas wistar foram divididas em cinco grupos (n=7 em cada grupo): controle e sedentários (C+S); tratados com CP e sedentário (CP+S); tratados com CP e submetidos ao LIT (CP+LIT); tratados com CP e submetidos ao MIT (CP+MIT) e tratados com CP e submetidos ao HIIT (CP+HIIT). Os protocolos de treinamentos consistiram de corrida em esteira motorizada, 5 dias por semana, por 8 semanas, antes do tratamento com CP. Ao final das 8 semanas de treinamento, as ratas receberam uma única injeção de CP (5 mg/kg i.p) ou solução salina, e 7 dias depois da injeção foram eutanasiadas. Amostras do fígado foram coletadas para avaliar a expressão do fator de transcrição nuclear kappa B (NF-κB), do receptor toll like 4 (TLR4), fator de necrose tumoral alfa (TNF-α), interleucina (IL)-1α, IL-1β, IL-6, IL-8 e IL-10, o número de células ED-1 positivas e marcadores de macrófagos M1 (iNOS) e M2 (arginase 1) no tecido hepático. Os nossos resultados mostram que o tratamento com a CP promoveu aumento de todos os marcadores pró-inflamatórios, incluindo TLR4/NF-κB, citocinas pró-inflamatórias, imunomarcação de células ED-1 positivas e expressão do marcador de macrófago do tipo M1 em relação ao grupo controle. No entanto, o HIIT foi o protocolo de exercício mais eficaz em reduzir o aumento de todos esses marcadores quando comparado aos protocolos LIT e MIT. Adicionalmente, o pré-condicionamento com o HIIT potencializou as expressões da citocina anti-inflamatória IL-10 e do marcador de macrófagos do tipo M2, ao passo em que reduziu a expressão do marcador de macrófagos do tipo M1 no tecido hepático. Desse modo, o presente estudo sugere que o pré-condicionamento físico com o HIIT foi mais eficaz em promover efeitos hepatoprotetores do que os protocolos de pré-condicionamentos com LIT e MIT, regulando importantes marcadores inflamatórios através da modulação da via de sinalização TLR4/NF-κB no tecido hepático de ratas tratadas com CP.pt_BR
dc.publisher.departmentInstituto Multidisciplinar em Saúde (IMS)pt_BR
dc.relation.referencesABASSI, M., M. et al. Effects of Cornus mas Fruit Hydro-Methanolic Extract on Liver Antioxidants and Histopathologic Changes Induced by Cisplatin in Rats. Ind J Clin Biochem, v. 35, n. 2, p. 218–224, 2020. ABDEL-DAIM, M., M. et al. Impact of garlic (Allium sativum) oil on cisplatin-induced hepatorenal biochemical and histopathological alterations in rats. Science of the Total Environment, v. 710, 2020. ABDEL-GAYOUM AA, AHMIDA MHS. Changes in the serum, liver, and renal cortical lipids and electrolytes in rabbits with cisplatin-induced nephrotoxicity. Turk J Med Sci, v.47: 1019-1027; 2017. AFSAR, T. et al. Modulatory influence of Acacia hydaspica R. Parker ethyl acetate extract against cisplatin inveigled hepatic injury and dyslipidemia in rats. In: BMC Complement Altern Med. v.17, n.1:307, 2017 AKCAY, A. et al. Mediators of Inflammation in Acute Kidney Injury. Mediators of Inflammation. vol. 2009, Artigo ID 137072, 12 páginas, 2009. ALHOSHANI, A. R. et al. Neuro-protective effect of rutin against Cisplatin-induced neurotoxic rat model. BMC Nephrol. v. 17, n. 472, 2017; AL-LAMKI, R. S.; MAYADAS, T. N. TNF receptors: signaling pathways and contribution to renal dysfunction. Kidney international, v. 87, n. 2, p. 281–296, 2015. AL-MAJED A.A. Carnitine deficiency provokes cisplatin-induced hepatotoxicity in rats. Basic Clin Pharmacol Toxicol. Mar;100(3):145-50; 2007. doi: 10.1111/j.1742-7843.2006.00024.x. PMID: 17309516. AL-MALKI A.L.; SAYED A.A. Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa-β. BMC Complement Altern Med. 14:282, 2014. doi:10.1186/1472-6882-14-282 ALI MONDAL S. et al. 17α-estradiol, a lifespan-extending compound, attenuates liver fibrosis by modulating collagen turnover rates in male mice. Am J Physiol Endocrinol Metab. 1;324(2):E120-E134, 2023 doi: 10.1152/ajpendo.00256.2022. ALMAZROO OA, MIAH MK, VENKATARAMANAN R. Drug Metabolism in the Liver. Clin Liver Dis. 21(1):1-20, 2017 doi: 10.1016/j.cld.2016.08.001. Epub 2016 Oct 15. PMID: 27842765. ALMEIDA, A. A. et al. Nephroprotective effect of exercise training in cisplatin-induced renal damage in mice: influence of training protocol. Brazilian Journal of Medical and Biological Research, v. 55, 2022. ALTINTAS F. et al. Swimming exercise restores damaging effects of fructose-enriched diet on the liver in rats. Tissue Cell. 78:101894, 2022 doi:10.1016/j.tice.2022.101894 AMACHER DE. Female gender as a susceptibility factor for drug-induced liver injury. Hum Exp Toxicol. 33(9), 928-39, 2014. doi: 10.1177/0960327113512860. AMARAL LSB. et al. Renal changes in the early stages of diet-induced obesity in ovariectomized rats. Physiol Res. 63(6), 723–32, 2014. BACCHI, E. et al. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized trial). Hepatology, 58, 1287–1295, 2013. BANO, N.; NAJAM, R. Histopathological and biochemical assessment of liver damage in albino Wistar rats treated with cytotoxic platinum compounds in combination with 5-fluorouracil. Arch Med Sci, v. 14, n. 4, p. 1092-1103, 2019. BARABAS, K. et al. Cisplatin: a review of toxicities and therapeutic applications. Veterinary and comparative oncology, v. 6, n. 1, p. 1-18, 2008. BARCELOS, R. et al. Diclofenac pretreatment effects on the toll-like receptor 4/nuclear factor kappa B-mediated inflammatory response to eccentric exercise in rat liver. Life sciences, v. 148, p. 247-253, 2016. BARNES, P. J.; KARIN, M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med.v.10, n. 336, p.1066-71, 1997. BARROSO, W., K., S. et al. Diretrizes Brasileiras de Hipertensão Arterial – 2020. Arquivos Brasileiros de Cardiologia, v. 116, n. 3, p. 516-658, 2021. BATACAN, R. B. et al. Effects of high-intensity interval training on cardiometabolichealth: a systematic review and meta-analysis of intervention studies. British journal of sports medicine, v. 51, n. 6, p. 494–503, 2017. BAY ML. et al. Voluntary Wheel Running Reduces the Acute Inflammatory Response to Liver Carcinogen in a Sex-specific Manner. Cancer Prev Res (Phila). 10(12):719-728, 2017 doi: 10.1158/1940-6207.CAPR-17-0075. BIANCHI, A. et al. Moderate exercise inhibits age-related inflammation, liver steatosis, senescence, and tumorigenesis. The Journal of Immunology, v. 206, n. 4, p. 904-916, 2021. BLAIR, S. N. Physical inactivity: the biggest public health problem of the 21st century, Br. J. Sports Med. v. 43 p.1-2. 2009. BLASER H. et al. TNF and ROS Crosstalk in Inflammation. Trends Cell Biol. Apr;26(4):249-261, 2016 doi: 10.1016/j.tcb.2015.12.002. BONAVIA A, SINGBARTL K. A review of the role of immune cells in acute kidney injury. Pediatr Nephrol. 33(10):1629-1639, 2018. doi: 10.1007/s00467-017-3774-5. BOSTROM P. et al. A PGC1α-dependent myokine that drives browning of white fat and thermogenesis. Nature. Jan 11;481(7382):463–8, 2012 BOUTCHER SH. High-intensity intermittent exercise and fat loss. Journal of obesity. 2011. doi:10.1155/2011/868305 BURRA P. et al. Special Interest Group Gender in Hepatology of the Italian Association for the Study of the Liver (AISF). Clinical impact of sexual dimorphism in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Liver Int. 41(8):1713-1733, 2021. doi: 10.1111/liv.14943. BUZZETTI E. et al. Gender differences in liver disease and the drug-dose gender gap. Pharmacol Res.120:97-108, 2017. doi: 10.1016/j.phrs.2017.03.014. CAVALLI G. et al. Interleukin 1α: a comprehensive review on the role of IL-1α in the pathogenesis and treatment of autoimmune and inflammatory diseases. Autoimmun Rev. 20(3):102763, 2021. doi: 10.1016/j.autrev.2021.102763. CATTADORI G. et al. Exercise and heart failure: an update. ESC Heart Fail. 5(2):222-232, 2018. doi: 10.1002/ehf2.12225. CHEN, W.-Y. et al. Cisplatin nephrotoxicity might have a sex difference. An analysis based on women’s sex hormone changes. Journal of cancer, v. 8, n. 19, p. 3939–3944, 2017. CHEN, S. et al. Deletion of TLR4 attenuates lipopolysaccharide-induced acute liver injury by inhibiting inflammation and apoptosis. Acta Pharmacologica Sinica, v. 42, n. 10, p. 1610-1619, 2021. CHOI JH. et al. Protective effects of Mg-CUD against D-galactosamine-induced hepatotoxicity in rats. Eur J Pharmacol. 657(1–3): 138–143, 2012. CHUN, Y. S.; LAURENT, A.; MARU, D.; VAUTHEY, J. N. Management of chemotherapy-associated hepatotoxicity in colorectal liver metastases. Lancet Oncol. 10, 278−286, 2009. COFFEY VG, HAWLEY JA. The molecular bases of training adaptation. Sports Med. 37:737–763,2007. doi: 10.2165/00007256-200737090-00001. COHEN, S. M.; LIPPARD, S. J. Cisplatin: from DNA damage to cancer chemotherapy. Prog. Nucleic Acid Res. Mol. Biol. 67, 93−130, 2001. COUNCIL, N. R. National Institutes of Health guide for the care and use of laboratory animals. 2011. COUPER, K. N.; BLOUNT, D. G.; RILEY, E. M. IL-10: the master regulator of immunity to infection. The Journal of Immunology, v. 180, n. 9, p. 5771-5777, 2008. CUI, J. et al. Effects of exercise on learning and memory, oxidative stress and nNOS expression in marginal division of striatum of ovariectomized rats. The Journal of sports medicine and physical fitness, v. 58, n. 3, p. 356-365, 2017. DASARI, S. TCHOUNWOU, P.B. Cisplatin in câncer therapy: Molecular mechanisms of action. Europen Journal of Pharmacology. 2014 DE CASTRO-DE-PAIVA, P. et al. (). Intermittent fasting, high-intensity interval training, or a combination of both have beneficial effects in obese mice with nonalcoholic fatty liver disease. The Journal of nutritional biochemistry. 104, 2022. Doi: 10.1016/j.jnutbio.2022.108997 DE JONGH, F. E. et al. Weekly high-dose cisplatin is a feasible treatment option: analysis on prognostic factors for toxicity in 400 patients. Br J Cancer, v. 88, p. 1199-1206, 2003. DINIZ TA. et al. Aerobic training improves NAFLD markers and insulin resistance through AMPK-PPAR-α signaling in obese mice. Life Sci. 1;266:118868, 2021. doi: 10.1016/j.lfs.2020.118868. DKHIL, M.A. et al. The potential role of Azadirachta indica treatment on cisplatin-induced hepatotoxicity and oxidative stress in female rats. Oxid Med Cell Longev. 2013:741817, 2013. doi: 10.1155/2013/741817. DOU L, SHI X, HE X, GAO Y. Macrophage Phenotype and Function in Liver Disorder. Front Immunol. 10:3112, 2020. doi:10.3389/fimmu.2019.03112 EASTMAN, A. Reevaluation of interaction of cis-dichloro (ethylenediamine) platinum(II) with DNA. Biochemistry 25, 3912−3915, 1986. EGAN B, ZIERATH JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab. 17:162–184, 2013. doi: 10.1016/j.cmet.2012.12.012. EKINCI, F. N. A. et al. The protective effects of p-coumaric acid on acute liver and kidney damages induced by cisplatin. Biomedicines, v. 5, n. 2, p. 18, 2017. EL-GIZAWY M.M. et al. Curcumin nanoparticles ameliorate hepatotoxicity and nephrotoxicity induced by cisplatin in rats. Naunyn Schmiedebergs Arch Pharmacol. 393(10):1941-1953, 2020. doi:10.1007/s00210-020-01888-0 EL-SHITANY N.A.; EID B. Proanthocyanidin protects against cisplatin-induced oxidative liver damage through inhibition of inflammation and NF-κβ/TLR-4 pathway. Environ Toxicol. 32(7):1952-1963, 2017. doi: 10.1002/tox.22418. ESHRAGHI-JAZI, F., et al. The protective role of endogenous nitric oxide donor (L-arginine) in cisplatin-induced nephrotoxicity: Gender related differences in rat model. J Res Med Sci. v. 16, n.11, p.1389-96, 2001. ESHRAGHI-JAZI, F.; NEMATBAKHSH, M. Sex difference in cisplatin-induced nephrotoxicity: Laboratory and clinical findings. Journal of toxicology, v. 2022, p. 3507721, 2022. FEALY, C. E. et al. Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease. Journal of Applied Physiology, v. 113, n. 1, p. 1-6, 2012 FIORENTINO, D. F.; BOND, M. W.; MOSMANN, T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. Journal of Experimental Medicine, v. 170, n. 6, p. 2081-2095, 1989. FORMIGARI G.P. et al. Renal protection induced by physical exercise may be mediated by the irisin/AMPK axis in diabetic nephropathy. Sci Rep. 31;12(1):9062, 2022. doi: 10.1038/s41598-022-13054-y. FRANCESCATO, H. D. C., et al. Previous Exercise Effects in Cisplatin-Induced Renal Lesions in Rats. Kidney Blood Press Res. v. 43, p. 582-593, 2018. FREDRICKSON G. et al. Exercise of high intensity ameliorates hepatic inflammation and the progression of NASH. Mol Metab. 53:101270, 2021. doi:10.1016/j.molmet.2021.101270 FRIEDENREICH, C. M.; RYDER-BURBIDGE, C.; MCNEIL, J. Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biologic mechanisms. Molecular oncology, v. 15, n. 3, p. 790–800, 2021. FULCO, B.C.W. et al. Pattern differences between newborn and adult rats in cisplatin-induced hepatorenal toxicity. Chemico-Biological Interactions, v. 294, p. 65-73, 2018. FULLER KNZ. et al. Estradiol Treatment or Modest Exercise Improves Hepatic Health and Mitochondrial Outcomes in Female Mice Following Ovariectomy. Am J Physiol Endocrinol Metab 320:E1020–e1031, 2021. doi: 10.1152/ajpendo.00013.2021 GAESSER GA.; ANGADI SS. High-intensity interval training for health and fitness: can less be more? J Appl Physiol (1985). 111(6):1540-1, 2011. doi: 10.1152/japplphysiol.01237.2011. GALMÉS-PASCUAL B.M. et al. 17β-Estradiol Ameliorates Lipotoxicity-Induced Hepatic Mitochondrial Oxidative Stress and Insulin Resistance. Free Radic Biol Med 150:148–60, 2020. doi: 10.1016/j.freeradbiomed.2020.02.016 GAO C. et al. Intensive Running Enhances NF-κB Activity in the Mice Liver and the Intervention Effects of Quercetin. Nutrients. 11;12(9):2770, 2020. doi: 10.3390/nu12092770. GHOSH S; KARIN M. Missing pieces in the NF-kappaB puzzle. Cell. 109 Suppl:S81-96, 2002. doi: 10.1016/s0092-8674(02)00703-1. GHOSH S. Cisplatin: The first metal based anticancer drug. Bioorg Chem. 88:102925, 2019. doi: 10.1016/j.bioorg.2019.102925. GIBALA MJ. et al.. Physiological adaptations to low‐volume, high‐intensity interval training in health and disease. J Physiol. 590:1077–1084, 2012. doi: 10.1113/jphysiol.2011.224725. GLASS O. et al. Serum Interleukin-8, Osteopontin, and Monocyte Chemoattractant Protein 1 Are Associated With Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Hepatol Commun. 2(11):1344-1355, 2018. doi: 10.1002/hep4.1237. GOLBAR H. M. et al. Immunohistochemical analyses of the kinetics and distribution of macrophages, hepatic stellate cells and bile duct epithelia in the developing rat liver. Exp Toxicol Pathol 64, 1–8, 2012. GOMEZ-CABRERA, M.; DOMENECH, E.; VIÑA, J. Moderate exercise is an antioxidant: Upregulation of antioxidant genes by training. Free Radical Biology & Medicine, 44, 126–131, 2008. GRIMBERT, S. et al. Effects of female sex hormones on mitochondria: possible role in acute fatty liver of pregnancy. American Journal of Physiology-Gastrointestinal and Liver Physiology, v. 268, n. 1, p. G107-G115, 1995. GUARINO, M. et al. Exercise attenuates the transition from fatty liver to steatohepatitis and reduces tumor formation in mice. Cancers 12(6), 2020. GUO, J.; FRIEDMAN, S. L. Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis. Fibrogenesis & tissue repair, 3, 1-19, 2010. HABIB SA. et al. The protective effect of protocatechuic acid on hepatotoxicity induced by cisplatin in mice. Life Sci. 277:119485, 2021. doi:10.1016/j.lfs.2021.119485 HAGAR H. et al. Inhibition of NF-κB and the oxidative stress -dependent caspase-3 apoptotic pathway by betaine supplementation attenuates hepatic injury mediated by cisplatin in rats. Pharmacol Rep. 71(6):1025-1033, 2019. doi: 10.1016/j.pharep.2019.06.003. HAJIGHASEM, A.; FARZANEGI, P.; MAZAHERI, Z. Effects of combined therapy with resveratrol, continuous and interval exercises on apoptosis, oxidative stress, and inflammatory biomarkers in the liver of old rats with non-alcoholic fatty liver disease. Archives of Physiology and Biochemistry, in Press, 2018. doi:10.1080/13813455.13812018.11441872. HAN D, et al. Signal transduction pathways involved in drug-induced liver injury. Handb Exp Pharmacol. (196):267-310, 2010. doi: 10.1007/978-3-642-00663-0_10. HANIGAN, M.H.; DEVARAJAN,P. Cisplatin nephrotoxicity: molecular mechanisms. Cancer Ther.; Athens, v.1, p.47-61, 2003. HASSAN, H.M. et al. Suppression of Cisplatin-Induced Hepatic Injury in Rats Through Alarmin High-Mobility Group Box-1 Pathway by Ganoderma lucidum: Theoretical and Experimental Study. Drug Des Devel Ther. 14:2335-2353, 2020. doi: 10.2147/DDDT.S249093. HAZELHOFF, M.H.; TORRES, A.M. Gender differences in mercury-induced hepatotoxicity: potential mechanisms. Chemosphere, v. 202, p. 330-338, 2018. HE G, KARIN M. NF-κB and STAT3 - key players in liver inflammation and cancer. Cell Res. 21(1):159-68, 2011. doi: 10.1038/cr.2010.183. HESHAM, A. AHMED; GHOBARA, MOHAMED M. Histological study of the effect of cisplatin on the liver of adult male albino rat. International Journal of Academic and Scientific Research, v. 1, n. 1, p. 22-33, 2013. HOSSEINI HM. et al. Ameliorative effects of high intensity interval training and Lactobacillus rhamnosus GG Protect against tetracycline-induced fatty liver in rats: a gene expression profiling comparative study. EXCLI J. 21:991-1006, 2022. doi: 10.17179/excli2022-4791. HU, N. et al. Phillygenin inhibits LPS-induced activation and inflammation of LX2 cells by TLR4/MyD88/NF-κB signaling pathway. Journal of ethnopharmacology, v. 248, p. 112361, 2020. HUBER Y, et al. Voluntary distance running prevents TNF-mediated liver injury in mice through alterations of the intrahepatic immune milieu. Cell Death Dis. 2017. doi: 10.1038/cddis.2017.266. HUNT CM. et al. Drug rechallenge following drug-induced liver injury. Hepatology. 2017. doi:10.1002/hep.29152 INCA- INSTITUTO NACIONAL DE CÂNCER. Estatística de Câncer (2021). Disponível em: < https://www.inca.gov.br/numeros-de-cancer> INGAWALE, D.K.; MANDLIK, S.K.; NAIK, S.R. Models of hepatotoxicity and the underlying cellular, biochemical and immunological mechanism(s): a critical discussion. Environ Toxicol Pharmacol. 37(1):118-33, 2014. doi: 10.1016/j.etap.2013.08.015. ISHIBE, T. et al. Reduced acetaminophen-induced liver injury in mice by genetic disruption of IL-1 receptor antagonist. Laboratory investigation, v. 89, n. 1, p. 68-79, 2009. IWAKIRI Y. Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase. Clin Mol Hepatol. 21(4):319-325, 2015. doi:10.3350/cmh.2015.21.4.319 JABLONSKI K.A. et al. Novel Markers to Delineate Murine M1 and M2 Macrophages. PLoS One. 10(12):e0145342, 2015. doi: 10.1371/journal.pone.0145342. JAMIESON, E. R.; LIPPARD, S. J. Structure, recognition, and processing of cisplatin-DNA adducts. Chem. Rev. 99, 2467−2498, 1999. JANG, H.R., RABB, H. Immune cells in experimental acute kidney injury. Nat. Rev. Nephrol. 11, 88-101, 2015. JELLEYMAN, C. et al. The effects of high-intensity interval training on glucose regulation and insulin resistance: a meta-analysis. Obesity Reviews 16(11):942e961, 2015. JEONG JH. et al. The effects of either resveratrol or exercise on macrophage infiltration and switching from M1 to M2 in high fat diet mice. J Exerc Nutrition Biochem. 19(2):65-72, 2015. doi: 10.5717/jenb.2015.15060203. JUNG, Y.; LIPPARD, S. J. Direct cellular responses to platinum-induced DNA damage. Chem. Rev. 107, 1387−1407, 2007. KAMPSHOFF, C., S. et al. Randomized controlled trial of the effects of high intensity and low-to-moderate intensity exercise on physical fitness and fatigue in cancer survivors: results of the Resistance and Endurance exercise After ChemoTherapy (REACT) study. BMC Med, v. 29, n. 13, 2015. KAWAGUCHI, T. et al.. Hybrid training of voluntary and electrical muscle contractions reduces steatosis, insulin resistance, and IL-6 levels in patients with NAFLD: A pilot study. Journal of Gastroenterology, 46, 746–757, 2011. KAWANISHI, N.; YANO, H.; MIZOKAMI, T.; TAKAHASHI, M.; OYANAGI, E.; SUZUKI, K. Exercise training attenuates hepatic inflammation, fibrosis and macrophage infiltration during diet induced-obesity in mice. Brain Behav Immun. 2012 Aug;26(6):931-41. doi: 10.1016/j.bbi.2012.04.006. Epub 2012 Apr 23. PMID: 22554494. KERR, J.; ANDERSON, C.; LIPPMAN, S. M. Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence. The lancet oncology. v. 18, n. 8, p. e457– e471, 2017 KHEDR L.H. et al. Crocin attenuates cisplatin-induced hepatotoxicity via TLR4/NF-κBp50 signaling and BAMBI modulation of TGF-β activity: Involvement of miRNA-9 and miRNA-29. Food Chem Toxicol. 140:111307, 2020 . doi: 10.1016/j.fct.2020.111307. KHOSRAVI M,S. et al. Hydration with Mannitol and Dextrose May Promote Cisplatin-Induced Nephrotoxicity: Test of Five Protocols of Hydration during Cisplatin Therapy in Rat Models. J Toxicol. 2021:5547341, 2021. doi: 10.1155/2021/5547341. KOCIBA, R. J.; SLEIGHT, S. D. Acute toxicologic and pathologic effects of cis-diamminedichloroplatinum (NSC-119875) in male rat. Cancer Chemother. Rep. 55, 1−8, 1971. KONO H, ROCK KL. How dying cells alert the immune system to danger. Nat Rev Immunol. 8: 279–289, 2008. KOPPELMAN B. et al. Interleukin-10 down-regulates MHC class II alphabeta peptide complexes at the plasma membrane of monocytes by affecting arrival and recycling. Immunity. 7(6):861-871, 1997. doi:10.1016/s1074-7613(00)80404-5 KRENKEL O, TACKE F. Liver macrophages in tissue homeostasis and disease. Nat Rev Immunol. 17(5):306-321, 2017. doi:10.1038/nri.2017.11 LAUNAY-VACHER, V. et al. Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemother. Pharmacol. 61, 903−909, 2008. LAYTON AT, SULLIVAN JC. Recent advances in sex differences in kidney function. Am J Physiol Renal Physiol. 316(2):F328-F331, 2019. doi: 10.1152/ajprenal.00584.2018. LEE JW. et al. Role of IL-1α in cisplatin-induced acute renal failure in mice. Korean J Intern Med. 26(2):187-94, 2011 . doi: 10.3904/kjim.2011.26.2.187. LEE, W.B. et al. Mincle-mediated translational regulation is required for strong nitric oxide production and inflammation resolution. Nat. Commun. 7, 11322, 2016. LEITE, A. B. et al. High-intensity interval training is more effective than continuous training to reduce inflammation markers in female rats with cisplatin nephrotoxicity. Life Sciences, v. 266, p. 118880, 2021. LI, W. et al. Human primary renal cells as a model for toxicity assessment of chemotherapeutic drugs. Toxicol in vitro, Oxford, v.20,n.5, p. 669-676, 2006. LI Q. et al. Irisin alleviates LPS-induced liver injury and inflammation through inhibition of NLRP3 inflammasome and NF-κB signaling. J Recept Signal Transduct Res. 41(3):294-303, 2021. doi: 10.1080/10799893.2020.1808675. LIMA-POSADA I. et al. Gender Differences in the Acute Kidney Injury to Chronic Kidney Disease Transition. Sci Rep. 7(1):12270, 2017. doi: 10.1038/s41598-017-09630-2.. LIN D. et al. Secreted IL-1α promotes T-cell activation and expansion of CD11b(+) Gr1(+) cells in carbon tetrachloride-induced liver injury in mice. Eur J Immunol. 45(7):2084-98, 2015. doi: 10.1002/eji.201445195. LINDEN, M.A. et al. Aerobic exercise training in the treatment of nonalcoholic fatty liver disease related fibrosis. Journal of Physiology 594(18): 5271e5284, 2016. LITTLE, J.P. et al. Effects of high-intensity interval exercise versus continuous moderate-intensity exercise on postprandial glycemic control assessed by continuous glucose monitoring in obese adults. Applied Physiology, Nutrition, and Metabolism. 39(7):835e841, 2014. LIVAK KJ, SCHMITTGEN TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25(4):402-8, 2001. doi: 10.1006/meth.2001.1262. LU Y.; CEDERBAUM AI. Cisplatin-induced hepatotoxicity is enhanced by elevated expression of cytochrome P450 2E1. Toxicol Sci. 89(2):515-23, 2006. doi: 10.1093/toxsci/kfj031. LU RJ. et al. Clinical characteristics of drug-induced liver injury and related risk factors. Exp Ther Med 12(4):2606–2616, 2016. doi:10.3892/etm.2016.3627 MA, X. et al. Puerarin attenuates cisplatin-induced rat nephrotoxicity: The involvement of TLR4/NF-κB signaling pathway. PLoS One, v. 12, n. 2, p. e0171612, 2017. MAEDA S. et al. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell.;121:977–990, 2005. MANOHAR, S.; LEUNG, N. Cisplatin nephrotoxicity: a review of the literature. Journal of nephrology, v. 31, n. 1, p. 15-25, 2018. MANSOUR, H.H.; HAFEZ, H.F.; FAHMY, N.M. Silyman modulates cisplatin-induced oxidative stress and hepatotoxicity in rats. J Biochem Mol Biol., Seoul Korean, v.39, n. 6, p. 656-61, 2006. MARCOS R. et al. Stereological assessment of sexual dimorphism in the rat liver reveals differences in hepatocytes and Kupffer cells but not hepatic stellate cells. J Anat. Jun;228(6):996-1005, 2016. doi: 10.1111/joa.12448. MARTINEZ, F. O. Regulators of macrophage activation. Eur J Immunol 41, 1531–34, 2011. MARTINS NM, SANTOS NA, CURTI C, BIANCHI ML, SANTOS AC. Cisplatin induces mitochondrial oxidative stress with resultant energetic metabolism impairment, membrane rigidification and apoptosis in rat liver. J Appl Toxicol. 28(3):337-44, 2008. doi: 10.1002/jat.1284. MARTLAND R. et al. Can high-intensity interval training improve physical and mental health outcomes? A meta-review of 33 systematic reviews across the lifespan. J Sports Sci. 38(4):430-469, 2020 . doi: 10.1080/02640414.2019.1706829. MENNECOZZI M. et al. Sex differences in liver toxicity-do female and male human primary hepatocytes react differently to toxicants in vitro? PLoS One. 10(4):e0122786, 2015. doi: 10.1371/journal.pone.0122786. MIYAGI, M.Y., et al. Long-term aerobic exercise protects against cisplatin-induced nephrotoxicity by modulating the expression of IL-6 and HO-1. PLoS One. v. 9 n.10, e108543, 2014. NAGAKAWA, J. et al. Interleukin-1 alpha enhances hepatotoxicity of tumor necrosis factor-alpha in galactosamine-sensitized mice. Immunopharmacology and immunotoxicology, 13(4), 485–498, 1991. doi:10.3109/08923979109019718 NASR, ASHRAF Y. "Morphological, biochemical, histological, and ultrastructural protective effects of misoprostol on cisplatin induced-hepatotoxicity in adult male rats." Saudi Med J 34.12, 1237-47, 2013. NEMATBAKHSH M. et al. Gender difference in Cisplatin-induced nephrotoxicity in a rat model: greater intensity of damage in male than female. Nephrourol Mon. 5(3):818-21, 2013. doi: 10.5812/numonthly.10128. NEUGARTEN J, GOLESTANEH L. Sex Differences in Acute Kidney Injury. Semin Nephrol. 2022 Mar;42(2):208-218. doi: 10.1016/j.semnephrol.2022.04.010. PMID: 35718367. NJOKU, D. B. et al. Suppressive and pro-inflammatory roles for IL-4 in the pathogenesis of experimental drug-induced liver injury. Eur J Immunol 39, 1652–63, 2009. OH, G. S. et al. Cisplatin-induced Kidney Dysfunction and Perspectives on Improving Treatment Strategies. In: Electrolyte Blood Press, v.12, n. 2, p. 55-65, 2014. OLIVEIRA C.A. et al. Benefits of high-intensity interval training compared to continuous training to reduce apoptotic markers in female rats with cisplatin nephrotoxicity - possible modulatory role of IL-11. Apoptosis. 28(3-4):566-575, 2023. doi: 10.1007/s10495-023-01816-6. OMAR H.A. et al. Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis. PLoS One. 11(3):e0151649, 2016. doi:10.1371/journal.pone.0151649 OSALI A. Aerobic exercise and nano-curcumin supplementation improve inflammation in elderly females with metabolic syndrome. Diabetol Metab Syndr. 12:26, 2020. doi:10.1186/s13098-020-00532-4 OSURU HP. et al. Moderate exercise-induced dynamics on key sepsis-associated signaling pathways in the liver. Crit Care. 27(1):266, 2023. doi:10.1186/s13054-023-04551-1 OUN, R.; MOUSSA, Y. E.; WHEATE, N. J. The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton transactions, v. 47, n. 19, p. 6645-6653, 2018. PAFFENBARGER, R. S. J.; HYDE, R.T.; WING, A.L.; HSIEH, C.C. Physical activity, all-cause mortality, and longevity of college alumni, N. Engl. J. Med. v. 314, p. 605–613, 1986. PELLO, O. M. et al. A glimpse on the phenomenon of macrophage polarization during atherosclerosis. Immunobiology 216, 1172–76, 2011. PERES LA, DA CUNHA AD JR. Acute nephrotoxicity of cisplatin: molecular mechanisms. J Bras Nefrol. 35(4):332-40, 2013. doi: 10.5935/0101-2800.20130052. PEZESHKI, Z. et al. Evidence Against Protective Role of Sex Hormone Estrogen in Cisplatin Induced Nephrotoxicity in Ovarectomized Rat Model. Toxicology International v. 20, n. 1, p. 43-47, 2013. PIGHON A. et al. Exercise training in ovariectomized rats stimulates estrogenic-like effects on expression of genes involved in lipid accumulation and subclinical inflammation in liver. Metabolism.;60(5):629-639, 2011. doi:10.1016/j.metabol.2010.06.012 PINTO AL, LIPPARD SJ. Binding of the antitumor drug cis-diamminedichloroplatinum(II) (cisplatin) to DNA. 4. 780(3):167-80, 1985. doi: 10.1016/0304-419x(85)90001-0. PRATIBHA, R. et al. Enzymatic studies of cisplatin induced oxidative stress in hepatic tissue of rats. Eur J Pharmacol. 532(3):290-3, 2006. doi: 10.1016/j.ejphar.2006.01.007. PAUNOVIĆ, M., G. et al. Evaluation of Toxic Effects of Novel Platinum (IV) Complexes in Female Rat Liver: Potential Protective Role of Resveratrol, Cell Biochemistry and Biophysics, 2020. POLYZOS SA. et al. Menopausal Hormone Therapy in Women With Dyslipidemia and Nonalcoholic Fatty Liver Disease. Hormones (Athens). 2022. doi: 10.1007/s42000-022-00369-8 QI, L., et al. Advances in toxicological research of the anticancer drug cisplatin. Chemical research in toxicology, v. 32, n. 8, p. 1469-1486, 2019. QU, X. et al. Astragaloside IV protects against cisplatin-induced liver and kidney injury via autophagy-mediated inhibition of NLRP3 in rats. Journal of Toxicological Sciences, v. 44, n. 3, p. 167–175, 2019. QUINTANILHA, J. C.F. et al. Involvement of cytochrome P450 in cisplatin treatment: implications for toxicity. Cancer Chemother. Pharmacol. 80, 223−233, 2017. RAHMAN N. et al. M1/M2-macrophage Polarization-based Hepatotoxicity in d-galactosamine-induced Acute Liver Injury in Rats. Toxicol Pathol. 46(7):764-776, 2018. doi: 10.1177/0192623318801574. RAMESH G, REEVES WB. TNFR2-mediated apoptosis and necrosis in cisplatin-induced acute renal failure. Am J Physiol Renal Physiol. 285(4):F610-F618, 2003. doi:10.1152/ajprenal.00101.2003 RASHID N.A. et al. Polygonum minus essential oil modulates cisplatin-induced hepatotoxicity through inflammatory and apoptotic pathways. Excli J. 19:1246-1265, 2020. doi:10.17179/excli2020-2355 REHMAN M.U. et al. Alleviation of hepatic injury by chrysin in cisplatin administered rats: probable role of oxidative and inflammatory markers. Pharmacol Rep. 66(6):1050-1059, 2014. doi:10.1016/j.pharep.2014.06.004 RODRÍGUEZ-ITURBE, B. et al. Oxidative Stress, Renal Infiltration of Immune Cells, and Salt-Sensitive Hypertension: all for one and one for all. In: American Journal of Physiology-Renal Physiology, v. 286, n. 4, p. 606-F616, 2004. ROGERS, N.M. et al. Dendritic cells and macrophages in the kidney: a spectrum of good and evil. Nat. Rev. Nephrol. 10, 625-643, 2014. ROSENBERG, B.; VAN CAMP, L.; KRIGAS, T. Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature, v. 205, n. 4972, p. 698-699, 1965. SABAG A, LITTLE JP, JOHNSON NA. Low-volume high-intensity interval training for cardiometabolic health. J Physiol. 2021. doi:10.1113/jp281210 SABAT, R. IL-10 family of cytokines. Cytokine & growth factor reviews, v. 21, n. 5, p. 315-324, 2010. SAKAMOTO M. et al.. Improvement of Portal Hypertension and Hepatic Blood Flow in Cirrhotic Rats by Oestrogen. Eur J Clin Invest 35:220–5, 2005. doi: 10.1111/j.1365-2362.2005.01476.x SAKURAI T. et al. Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis. Cancer Cell. 14(2):156-65, 2008. doi: 10.1016/j.ccr.2008.06.016. SALERNI S. et al. The different role of sex hormones on female cardiovascular physiology and function: not only oestrogens. Eur J Clin Invest. 45(6):634-45, 2015. doi: 10.1111/eci.12447. SALLIS, R. et al. Strategies for promoting physical activity in clinical practice. Prog Cardiovasc Dis. v. 57, n. 4, p. 375-86, 2015. SAMPAIO IBM. Estatística Aplicada À Experimentação Animal. 3.ed. Belo Horizonte: FEP MVZ; 2007. SATAPATHY, S.K. et al. Drug-induced fatty liver disease: An overview of pathogenesis and management. Ann Hepatol. 14(6):789-806, 2015. doi: 10.5604/16652681.1171749. SHEIKH R. et al. Moderate and high-intensity interval training protect against diabetes-induced modulation of hepatic CD86 and CD206 expression associated with the amelioration of insulin resistance and inflammation in rats. Immunobiology. 228(6):152745, 2023. doi:10.1016/j.imbio.2023.152745 SHI, P. et al. Avicularin alleviates acute liver failure by regulation of the TLR4/MyD88/NF‐κB and Nrf2/HO‐1/GPX4 pathways to reduce inflammation and ferroptosis. Journal of Cellular and Molecular Medicine, v. 27, n. 21, p. 3326-3338, 2023. SICA A, MANTOVANI A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 122(3):787-95, 2012. doi: 10.1172/JCI59643. SIDDIK, Z. H. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22, 7265−7279, 2003 SILVA L.L.S. et al. Effects of Aerobic Exercise Protocol on Genes Related to Insulin Resistance and Inflammation in the Pancreas of ob/ob Mice with NAFLD. Clin Exp Gastroenterol. 13:223-234, 2020. doi:10.2147/CEG.S242393 SOLTANI, N. et al. Assessment of the effect of short-term combined high-intensity interval training on TLR4, NF-κB and IRF3 expression in young overweight and obese girls. Public Health Genomics, v. 23, n. 1-2, p. 26-36, 2020. SOLTANI, N. et al. Resistance exercise training augments the immunomodulatory adaptations to aerobic high-intensity interval training: HIIT prescription, TLR4 pathway, and negative regulatory proteins. European Journal of Sport Science, p. 1-24, 2023. STEWART, D.J.; BENJAMIN, R. S.; LUNA, M. Human tissue distribution of platinum after cis-diamminedichloroplatinum. Cancer Chemother. Pharmacol. 10, 51–54, 1982 STIRNIMANN G, KESSEBOHM K, LAUTERBURG B. Liver injury caused by drugs: an update. Swiss Med Wkly. 140:w13080, 2010. doi: 10.4414/smw.2010.13080. SULTANOVA RF. et al. Sex differences in renal mitochondrial function: a hormone-gous opportunity for research. Am J Physiol Renal Physiol. 319(6):F1117-F1124, 2020. doi: 10.1152/ajprenal.00320.2020. SUN, M. et al. Aerobic Exercise Ameliorates Liver Injury in Db/Db Mice by Attenuating Oxidative Stress, Apoptosis and Inflammation Through the Nrf2 and JAK2/STAT3 Signalling Pathways. Journal of Inflammation Research, p. 4805-4819, 2023. TADAGAVADI RK, REEVES WB. Endogenous IL-10 attenuates cisplatin nephrotoxicity: role of dendritic cells. J Immunol. 185(8):4904-4911, 2010. doi:10.4049/jimmunol.1000383 THOMPSON, W. R. et al. Exercise Is Medicine. Am J Lifestyle Med. v. 14 n. 5, p. 511-523, 2020. TOTHILL, P. et al. The long-term retention of platinum in human tissues following the administration of cisplatin or carboplatin for cancer chemotherapy. Eur J Cancer. 28A(8-9):1358-61, 1992. doi: 10.1016/0959-8049(92)90519-8. TOYODA Y. et al.. Mechanism of Exacerbative Effect of Progesterone on Drug-Induced Liver Injury. Toxicol Sci 126:16–27, 2012. doi: 10.1093/toxsci/kfr326 TSANG RY, AL-FAYEA T, AU HJ. Cisplatin overdose: toxicities and management. Drug Saf. 32(12):1109-1122, 2009. doi:10.2165/11316640-000000000-00000 UEBI T, UMEDA M, IMAI T. Estrogen Induces Estrogen Receptor Alpha Expression and Hepatocyte Proliferation in the Livers of Male Mice. Genes Cells 20:217–23, 2015. doi: 10.1111/gtc.12214 UEHARA, T. et al. Comparative Nephrotoxicity of Cisplatin and Nedaplatin: Mechanisms and Histopathological Characteristics. In: J Toxicol Pathol, v. 24, p. 87–94, 2011. UN, H. et al. A novel effect of Aprepitant: Protection for cisplatin-induced nephrotoxicity and hepatotoxicity, European Journal of Pharmacology, v. 880, 2020. VASILI, A. et al. The effect of aerobic exercise on hepatotoxicity induced by intratracheal instillation of iron oxide nanoparticles in Wistar rats. Gen Physiol Biophys. 35(1):35-43, 2016. doi: 10.4149/gpb_2015031. WANG, D.; LIPPARD, S.J. Cellular processing of platinum anticâncer drugs. Nat Ver. Rug Discov., London, v.4, n. 4, p. 307-20, 2005. WANG, F. et al.Kinetics of aquation and anation of Ruthenium(II) arene anticancer complexes, acidity and X-ray structures of aqua adducts. Chem. - Eur. J. 9, 5810−5820, 2003. WANG G. et al. Resveratrol mitigates lipopolysaccharide-mediated acute inflammation in rats by inhibiting the TLR4/NF-κBp65/MAPKs signaling cascade. Sci Rep. 7:45006, 2017. doi: 10.1038/srep45006. WANG, N. et al. High-intensity interval versus moderate-intensity continuous training: Superior metabolic benefits in diet-induced obesity mice. Life sciences, 191, 122–131, 2017. doi: 10.1016/j.lfs.2017.08.023 WANG, L. et al. Berberine inhibits liver damage in rats with non-alcoholic fatty liver disease by regulating TLR4/MyD88/NF-κB pathway. The Turkish Journal of Gastroenterology, v. 31, n. 12, p. 902, 2020. WANG W.W. et al. IL-10 from dendritic cells but not from T regulatory cells protects against cisplatin-induced nephrotoxicity. PLoS One. 15(9), 2020. doi:10.1371/journal.pone.0238816 WANG, Y. et al. HIIT Ameliorates Inflammation and Lipid Metabolism by Regulating Macrophage Polarization and Mitochondrial Dynamics in the Liver of Type 2 Diabetes Mellitus Mice. Metabolites, 13(1), 14, 2022. doi: 10.3390/metabo13010014 WANG T. et al. FNDC5/Irisin Inhibits the Inflammatory Response and Mediates the Aerobic Exercise-Induced Improvement of Liver Injury after Myocardial Infarction. Int J Mol Sci. 24(4):4159, 2023. doi: 10.3390/ijms24044159. WANG Y.H. et al. The high level of IL-1β in the serum of ACLF patients induces increased IL-8 expression in hUC-MSCs and reduces the efficacy of hUC-MSCs in liver failure. Stem Cell Res Ther. 14(1):231, 2023. doi: 10.1186/s13287-023-03455-9. WASEEM, M. et al.. Cisplatin hepatotoxicity mediated by mitochondrial stress. Drug Chem. Toxicol. 38, 452−459, 2015. WEILER N. et al. The Epidemiology of Acute Liver Failure. Dtsch Arztebl Int. 117(4):43-50, 2020. doi: 10.3238/arztebl.2020.0043. WERMAN A, et al. The precursor form of IL-1alpha is an intracrine proinflammatory activator of transcription. Proc Natl Acad Sci U S A. 101(8):2434-9, 2004. doi: 10.1073/pnas.0308705101. WIJESUNDERA K.K. et al. M1- and M2-macrophage polarization in thioacetamide (TAA)-induced rat liver lesions; a possible analysis for hepato-pathology. Histol Histopathol. 29(4):497-511, 2014. doi: 10.14670/HH-29.10.497. WOLF E. et al. Vascular type 1 angiotensin receptors control blood pressure by augmenting peripheral vascular resistance in female mice. Am J Physiol Renal Physiol. Oct 1;315(4):F997-F1005, 2018. doi: 10.1152/ajprenal.00639.2017. XU L. et al. The Hepatoprotective and Hepatotoxic Roles of Sex and Sex-Related Hormones. Front Immunol. 13:939631, 2022. doi: 10.3389/fimmu.2022.939631. YANG X. et al.. 17β-Estradiol protects the liver against cold ischemia/reperfusion injury through the Akt kinase pathway. J Surg Res. 178(2):996-1002. doi: 10.1016/j.jss.2012.07.007, 2012. YAO, L. et al. Piceatannol alleviates liver ischaemia/reperfusion injury by inhibiting TLR4/NF-κB/NLRP3 in hepatic macrophages. European Journal of Pharmacology, v. 960, p. 176149, 2023. YAO J. et al. Effect of aerobic and resistance exercise on liver enzyme and blood lipids in Chinese patients with nonalcoholic fatty liver disease: a randomized controlled trial. Int J Clin Exp Med 11(5):4867–4874, 2018. YAZDANI HO. et al. Exercise Training Decreases Hepatic Injury and Metastases Through Changes in Immune Response to Liver Ischemia/Reperfusion in Mice. Hepatology. 73(6):2494-2509, 2021. doi: 10.1002/hep.31552. YILMAZ, H.R. et al.The activities of liver adenosine deaminase, xanthineoxidase, catalase, superoxide dismutase enzyme sand the levels of malondialdehyde and nitric oxide after cisplatin toxicity in rats: protective effect of caffeicacidphenethyl ester. Toxicol.Ind.Health 21,67–73, 2005. YU, Y. et al. Exercise alleviates the apolipoprotein A5-toll-like receptor 4 axis impairment in mice with high-fat diet-induced non-alcoholic steatohepatitis. Frontiers in Physiology, v. 12, p. 783341, 2021. YU, Y. et al. Moderate exercise relieves fluoride-induced liver and kidney inflammatory responses through the IKKβ/NFκB pathway. Environ Sci Pollut Res 29, 78429–78443, 2022. doi: 10.1007/s11356-022-21360-1 YU X. et al. Comparative efficacy of exercise training processes in improving nonalcoholic fatty liver disease: a systematic review and meta-analysis. Ir J Med Sci. 192(1):131-142, 2023. doi: 10.1007/s11845-022-02988-x. ZEYNALI F, NOROOZI J, PEZESHKI Z, NEMATBAKHSH M. Sex-related Difference in Protective Role of Aerobic Exercise against Cisplatin-induced Hepatotoxicity. Int J Prev Med. 2016;7:84. Published 2016 Jun 20. doi:10.4103/2008-7802.184312 ZHANG B. et al. TLR4 signaling mediates inflammation and tissue injury in nephrotoxicity. J Am Soc Nephrol. 19: 923–932, 2008. ZHANG, C. et al. Macrophage-derived IL-1α promotes sterile inflammation in a mouse model of acetaminophen hepatotoxicity. Cellular & molecular immunology, 15(11), 973–982, 2018. doi: 10.1038/cmi.2017.22 ZHOU D. et al. Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways. Cell Signal. 26(2):192-197, 2014. doi:10.1016/j.cellsig.2013.11.004 ZHOU X. et al. Dihydromyricetin-Encapsulated Liposomes Inhibit Exhaustive Exercise-Induced Liver Inflammation by Orchestrating M1/M2 Macrophage Polarization. Front Pharmacol. 13:887263, 2022. doi: 10.3389/fphar.2022.887263. ZHU W. et al. Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2. Cells. 10(12):3306, 2021. doi: 10.3390/cells10123306. ZIMMERMANN H.W. et al. Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis. PLoS One. 6(6):e21381, 2011. doi: 10.1371/journal.pone.0021381.pt_BR
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