{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:02:54Z","timestamp":1790290974501,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,8]],"date-time":"2024-09-08T00:00:00Z","timestamp":1725753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pr\u00f3-Reitoria de Pesquisa da Universidade Federal de Mato Grosso (Propeq-UFMT)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Cyclophosphamide (CPA) is an alkylating agent used as a chemotherapy agent in the treatment of cancer, but it has immunosuppressive effects. Protium heptaphyllum (P. heptaphyllum) is a plant rich in triterpenes and flavonoids, with some bioactive and therapeutic properties presented in the literature. Thus, the present study aimed to investigate the chemoprotective potential of P. heptaphyllum extract inserted into liposomes against oxidative damage chemically induced by CPA. Male Swiss mice received 1.5 mg\/kg of P. heptaphyllum liposomes as a pre-treatment for 14 consecutive days (via gavage) and 100 mg\/kg of CPA in a single dose (via intraperitoneal) on the 15th day. After the experimental period, blood and organ samples were collected for histopathological and biochemical analyses, including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), ascorbic acid (ASA), carbonyl protein, cytokine measurement, and micronucleus testing. The results showed that liposomes containing P. heptaphyllum extract have an antimutagenic effect against damage induced to DNA by CPA, and that they also protect against oxidative stress, as verified by the increase in the antioxidant enzymes SOD and GPx. The improvement in alkaline phosphatase and creatinine markers suggests a beneficial effect on the liver and kidneys, respectively. However, the depletion of GSH in the liver and brain suggests the use of antioxidants for the metabolism of molecules generated in these tissues. In general, these data show good prospects for the use of P. heptaphyllum liposomes as a cancer chemoprotective agent, as well as possible antioxidant action, conceivably attributed to the flavonoids present in the plant extract.<\/jats:p>","DOI":"10.3390\/biology13090706","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T05:06:06Z","timestamp":1725858366000},"page":"706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Study of Liposomes Containing Extract from the Leaves of Protium heptaphyllum (Aubl.) March in Animals Submitted to a Mutagenic Model Induced by Cyclophosphamide"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7890-6230","authenticated-orcid":false,"given":"Nai\u00e9le Sartori","family":"Patias","sequence":"first","affiliation":[{"name":"Postgraduate Program in Biotechnology and Biodiversity of the Pro Centro-Oeste Network, Federal University of Mato Grosso, Sinop 78550-728, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5070-0043","authenticated-orcid":false,"given":"Val\u00e9ria Dornelles Gindri","family":"Sinhorin","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biotechnology and Biodiversity of the Pro Centro-Oeste Network, Federal University of Mato Grosso, Sinop 78550-728, Brazil"},{"name":"Department of Chemistry, Institute of Exact and Earth Sciences, Federal University of Mato Grosso, Cuiab\u00e1 78060-719, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana J\u00falia Lopes Braga","family":"Ferneda","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Federal University of Mato Grosso, Sinop 78550-728, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Maur\u00edcio Andrade","family":"Ferneda","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Federal University of Mato Grosso, Sinop 78550-728, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Mariko","family":"Sugui","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Federal University of Mato Grosso, Sinop 78550-728, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4339-1307","authenticated-orcid":false,"given":"Stela Regina","family":"Ferrarini","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Federal University of Mato Grosso, Sinop 78550-728, Brazil"},{"name":"Institute of Health Sciences, Federal University of Mato Grosso, Sinop 78550-728, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisele Facholi","family":"Bomfim","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Federal University of Mato Grosso, Sinop 78550-728, Brazil"},{"name":"Institute of Health Sciences, Federal University of Mato Grosso, Sinop 78550-728, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2979-9058","authenticated-orcid":false,"given":"Joaz Wellington","family":"Lopes","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Federal University of Mato Grosso, Sinop 78550-728, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia Aline Bobbi","family":"Antoniassi","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Federal University of Mato Grosso, Sinop 78550-728, Brazil"},{"name":"Animal Pathology Laboratory, Federal University of Mato Grosso, Sinop 78550-728, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Cavalheiro","sequence":"additional","affiliation":[{"name":"Institute of Natural, Human and Social Sciences, Federal University of Mato Grosso, Sinop 78550-728, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson Lu\u00eds de Campos","family":"Domingues","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biotechnology and Biodiversity of the Pro Centro-Oeste Network, Federal University of Mato Grosso, Sinop 78550-728, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4133-8994","authenticated-orcid":false,"given":"Adilson Paulo","family":"Sinhorin","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biotechnology and Biodiversity of the Pro Centro-Oeste Network, Federal University of Mato Grosso, Sinop 78550-728, Brazil"},{"name":"Institute of Natural, Human and Social Sciences, Federal University of Mato Grosso, Sinop 78550-728, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1590\/S1984-82502009000200017","article-title":"Toxic effects of different doses of cyclophosphamide on the reproductive parameters of male mice","volume":"45","author":"Kanno","year":"2009","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_2","first-page":"740","article-title":"Cyclophosphamide related toxicity; a systematic review","volume":"6","author":"Alrefaei","year":"2022","journal-title":"Int. J. Med. Dev. Ctries."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/tcm.1770050202","article-title":"Cyclophosphamide teratogenesis: A review","volume":"5","author":"Mirkes","year":"1985","journal-title":"Teratog. Carcinog. Mutagen."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"131","DOI":"10.12816\/0009340","article-title":"Cytotoxic and anti-tumor effects of the chemotherapeutic drug cyclophosphamide in tumor bearing mice is time and dose dependent","volume":"62","author":"Salem","year":"2014","journal-title":"Egypt. J. Zool."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jep.2005.01.036","article-title":"Protective effect of alpha- and beta-amyrin, a triterpene mixture from Protium heptaphyllum (Aubl.) March. trunk wood resin, against acetaminophen-induced liver injury in mice","volume":"98","author":"Oliveira","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1007\/s11427-020-1799-y","article-title":"Natural product sciences: An integrative approach to the innovations of plant natural products","volume":"63","author":"Shen","year":"2020","journal-title":"Sci. China Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4660","DOI":"10.1002\/ptr.7099","article-title":"Natural products: A lead for drug discovery and development","volume":"35","author":"Chopra","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/S2222-1808(14)60760-X","article-title":"Sedative, membrane stability, cytotoxic and antioxidant properties of methanol extract of leaves of Protium serratum Wall","volume":"4","author":"Islam","year":"2014","journal-title":"Asian Pac. J. Trop. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/fcp.12402","article-title":"Pharmacological effects of the isomeric mixture of alpha and beta amyrin from Protium heptaphyllum: A literature review","volume":"33","author":"Nogueira","year":"2019","journal-title":"Fundam. Clin. Pharm."},{"key":"ref_10","first-page":"223","article-title":"Volatile metabolites present in Protium heptaphyllum (Aubl.) March. collected in Tame (Arauca\u2014Colombia)","volume":"11","year":"2012","journal-title":"Lat. Am. Caribb. Bull. Med. Aromat. Plants"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1590\/S0100-40422002000700006","article-title":"Secondary metabolites of Protium heptaphyllum March","volume":"25","author":"Bandeira","year":"2002","journal-title":"Quim. Nova"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1590\/S0044-59672010000100029","article-title":"Chemical composition of the essential oils from two subspecies of Protium heptaphyllum","volume":"40","author":"Marques","year":"2010","journal-title":"Acta Amaz."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1590\/S0100-40422000000500010","article-title":"Triterpenes from the resin of Protium heptaphyllum March (Burseraceae): Characterization in binary mixtures","volume":"23","author":"Maia","year":"2000","journal-title":"Qu\u00edm. Nova"},{"key":"ref_14","first-page":"715","article-title":"Identification of flavonoids by lc-ms\/ms in leaves extract from Protium heptaphyllum (Aubl.) March and antioxidant activity in mice","volume":"11","author":"Patias","year":"2021","journal-title":"Nat. Prod. J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Devi, S., Kumar, V., Singh, S.K., Dubey, A.K., and Kim, J.J. (2021). Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders. Biomedicines, 9.","DOI":"10.3390\/biomedicines9020099"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S398","DOI":"10.1016\/S1995-7645(14)60265-0","article-title":"Phytochemical screening and analysis of antioxidant properties of aqueous extract of wheatgrass","volume":"7S1","author":"Durairaj","year":"2014","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bishnu, K., and Jyoti, S. (2023). A Review Study of Importance of Herbal Medicine. Int. J. Multidiscip. Res., 5.","DOI":"10.36948\/ijfmr.2023.v05i01.1667"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Patias, N.S., Queiroz, E.A.I.F., Ferrarini, S.R., Bomfim, G.F., Aguiar, D.H., Sinhorin, A.P., Bello, A.A., Silva, G.V.F., Cavalheiro, L., and Sinhorin, V.D.G. (2024). Effect of liposomal extract of Protium heptaphyllum (Alb.) March in the treatment of obesity induced by a high-calorie diet. Biology, 13.","DOI":"10.3390\/biology13070535"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.2174\/1570180820666230308105723","article-title":"Application of Nanotechnology for Herbal Medicine Development: A Review","volume":"21","author":"Anand","year":"2023","journal-title":"Lett. Drug Des. Discov."},{"key":"ref_20","first-page":"60","article-title":"Lipid nanocarriers encapsulating herbal drugs for brain diseases therapy","volume":"7","author":"Gad","year":"2023","journal-title":"Arch. Pharm. Sci. Ain Shams Univ."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jha, S., and Halder, M. (2023). Medicinal Plants and Bioactive Phytochemical Diversity: A Fountainhead of Potential Drugs against Human Diseases. Medicinal Plants: Biodiversity, Biotechnology Conservation, Springer.","DOI":"10.1007\/978-981-19-9936-9_2"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hua, S., and WU, S.Y. (2013). The use of lipid-based nanocarriers for targeted pain therapies. Front. Pharmacol., 4.","DOI":"10.3389\/fphar.2013.00143"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/0378-8741(83)90050-8","article-title":"The pharmacological evaluation of natural products\u2014General and specific approaches to screening ethnophar-maceuticals","volume":"8","author":"Malone","year":"1983","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","first-page":"711","article-title":"Toxic Effects of Different Doses of Cyclophosphamide on Liver and Kidney Tissue in Swiss Albino Mice: A Histopathological Study","volume":"28","author":"Bhat","year":"2018","journal-title":"Ethiop. J. Health Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0165-1218(87)90016-4","article-title":"Guidelines for the conduct of micronucleus assay in mammalian bone marrow erythrocytes","volume":"189","author":"MacGregor","year":"1987","journal-title":"Mutat. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/0003-2697(72)90451-4","article-title":"Enthalpy of decomposition of hydrogen peroxide by catalase at 25 degrees C (with molar extinction coefficients of H2O2 solutions in the UV)","volume":"49","author":"Nelson","year":"1972","journal-title":"Anal. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3170","DOI":"10.1016\/S0021-9258(19)45228-9","article-title":"The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase","volume":"247","author":"Misra","year":"1972","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7130","DOI":"10.1016\/S0021-9258(19)42083-8","article-title":"Glutathione S-transferases. The first enzymatic step in mercapturic acid formation","volume":"249","author":"Habig","year":"1974","journal-title":"J. Biol. Chem."},{"key":"ref_29","first-page":"158","article-title":"Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase","volume":"70","author":"Paglia","year":"1967","journal-title":"J. Lab. Clin. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","article-title":"Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman\u2019s reagent","volume":"25","author":"Sedlack","year":"1968","journal-title":"Anal Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/9780470110171.ch5","article-title":"Chemical determination of ascorbic, dehydroascorbic, and diketogulonic acids","volume":"1","author":"Roe","year":"1954","journal-title":"Methods Biochem. Anal."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/S0076-6879(78)52032-6","article-title":"Microsomal lipid peroxidation","volume":"52","author":"Buege","year":"1978","journal-title":"Methods Enzymol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jchromb.2015.11.052","article-title":"A step-by-step protocol for assaying protein carbonylation in biological samples","volume":"1019","author":"Colombo","year":"2016","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e06927","DOI":"10.1590\/1678-5150-pvb-6927","article-title":"Down the rabbit hole: A quick guide for histopathology description","volume":"41","author":"Barros","year":"2021","journal-title":"Pesq. Vet. Bras."},{"key":"ref_36","unstructured":"Pereira, C.A.B., and Rabello, G.M.N. (1991). Statistical test to compare proportions in cytogenetic problems. Mutagenesis, carcinogenesis and teratogenesis: Methods and evaluation criteria. Ribeir\u00e3o Preto. Braz. Soc. Genet., 113\u2013121."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0165-1110(90)90039-E","article-title":"Antimutagenicity profiles for some model compounds","volume":"1","author":"Waters","year":"1990","journal-title":"Mutat. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ranjbar, S., Emamjomeh, A., Sharifi, F., Zarepour, A., Aghaabbasi, K., Dehshahri, A., Sepahvand, A.M., Zarrabi, A., Beyzaei, H., and Zahedi, M.M. (2023). Lipid-Based Delivery Systems for Flavonoids and Flavonolignans: Liposomes, Nanoemulsions, and Solid Lipid Nanoparticles. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071944"},{"key":"ref_39","first-page":"1","article-title":"Stimulation of Hepatocytes Repair by Fruit Juice of Opuntia ficus indica in Anti Cancer Drug Cyclophosphamide (CP)-Induced Liver Toxicity in Mice","volume":"10","author":"Shawagfeh","year":"2016","journal-title":"Annu. Res. Rev. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Roszkowski, S. (2023). Application of Polyphenols and Flavonoids in Oncological Therapy. Molecules, 28.","DOI":"10.3390\/molecules28104080"},{"key":"ref_41","first-page":"1","article-title":"Effect of Cyclophosphamide and Its Combination with Metformin on the Survival Rate in Mice","volume":"30","author":"Alhowail","year":"2019","journal-title":"J. Pharm. Res. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"113879","DOI":"10.1016\/j.fct.2023.113879","article-title":"Biflavonoid quercetin protects against cyclophosphamide-induced organ toxicities via modulation of inflammatory cytokines, brain neurotransmitters, and astrocyte immunoreactivity","volume":"178","author":"Onaolapo","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"ref_43","first-page":"4655","article-title":"Toxic effects of Cyclophosphamide on Hepatic and Kidney tissues in Albino Mice Model","volume":"15","author":"Zahraa","year":"2022","journal-title":"Res. J. Pharm. Technol."},{"key":"ref_44","first-page":"18","article-title":"The Influence of Cyclophosphamide on Growth Peripheral Blood Biochemidtry Index and Organ Coefficient of SD Rat","volume":"37","author":"Ying","year":"2010","journal-title":"Chin. J. Cancer"},{"key":"ref_45","unstructured":"Golan, E.D., Tashjian, H.A., Armstrong, J.E., and Armstrong, W.A. (2014). Princ\u00edpios de Farmacologia: A Base Fisiopatol\u00f3gica da Farmacoterapia, Guanabara Koogan. [3rd ed.]."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e34702","DOI":"10.15448\/1980-6108.2020.1.34702","article-title":"Antioxidant potential of Carica papaya Linn (Caricaceae) leaf extract in mice with cyclophosphamide induced oxidative stress","volume":"30","author":"Luiz","year":"2020","journal-title":"Sci. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/03601234.2022.2045841","article-title":"In vivo mutagenic effects and oxidative stress parameters evaluation of cypermethrin and benzoate of emamectin and their mixtures in female mice","volume":"57","author":"Bragante","year":"2022","journal-title":"J. Environ. Sci. Health Part B"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"251","DOI":"10.31413\/nat.v11i2.15376","article-title":"Prophylactic action of the isotonic drink made from the skins of the fruit of Oenocarpus bacaba Mart. (Arecaceae) against cyclophosphamide-induced oxidative stress in mice","volume":"11","author":"Sinhorin","year":"2024","journal-title":"Native"},{"key":"ref_49","unstructured":"Ribeiro, L.R., Salvadori, D.M., and Marques, E.K. (2024). Mutag\u00eanse Ambiental, Editora Ulbra. [1st ed.]. Available online: https:\/\/www.researchgate.net\/publication\/284581917_Mutagenese_Ambiental."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.fct.2004.09.011","article-title":"Evaluation of beta-myrcene, alpha-terpinene and (+)- and (\u2212)-alpha-pinene in the Salmonella\/microsome assay","volume":"43","author":"Viana","year":"2005","journal-title":"Food Chem. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"232","DOI":"10.4103\/japtr.JAPTR_380_20","article-title":"Antimutagenic activity of nanoparticles of Rhaphidophora pinnata leaves in mice using micronucleus assay","volume":"12","author":"Masfria","year":"2021","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_52","first-page":"80","article-title":"Evaluation of Mutagenic Effect (Antimutagenic) of Dalbergia Latifolia on Swiss Albino Mice","volume":"7","author":"Yadav","year":"2015","journal-title":"Int. J. Toxicol. Pharmacol. Res."},{"key":"ref_53","first-page":"105","article-title":"Evaluation of Antimutagenic Effect of Flavonoid of Kigelia Africana on Swiss-Albino Mice","volume":"21","author":"Vasantha","year":"2013","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"S42","DOI":"10.4103\/0973-1296.176113","article-title":"Essential Oil from the Resin of Protium heptaphyllum: Chemical Composition, Cytotoxicity, Antimicrobial Activity, and Antimutagenicity","volume":"12","author":"Lima","year":"2016","journal-title":"Pharmacogn. Mag."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1590\/S0102-695X2011005000117","article-title":"Gastroprotective effects of essential oil from Protium heptaphyllum on experimental gastric ulcer models in rats","volume":"21","author":"Araujo","year":"2011","journal-title":"Braz. J. Pharmacogn."},{"key":"ref_56","first-page":"117","article-title":"Anti-bacterial and anti-oxidant activities of the essential oil of resin of Protium heptaphyllum","volume":"1","author":"Bandeira","year":"2006","journal-title":"Nat. Prod. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s10534-005-0858-7","article-title":"Role of the alkali labile sites, reactive oxygen species and antioxidants in DNA damage induced by methylated trivalent metabolites of inorganic arsenic","volume":"18","author":"Valverde","year":"2005","journal-title":"Biometals"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.chemosphere.2011.02.025","article-title":"Assessing the genotoxic potentials of arsenic in tilapia (Oreochromis mossambicus) using alkaline comet assay and micronucleus test","volume":"84","author":"Ahmed","year":"2011","journal-title":"Chemosphere"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1007\/s10646-012-0907-2","article-title":"DNA damage and oxidative stress induced by endosulfan exposure in zebrafish (Danio rerio)","volume":"21","author":"Shao","year":"2012","journal-title":"Ecotoxicology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4","DOI":"10.46568\/bios.v2i1.40","article-title":"Estresse oxidativo: Uma espada de dois gumes","volume":"2","author":"Abbas","year":"2024","journal-title":"BioSight"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Sadasivam, N., Kim, Y.J., Radhakrishnan, K., and Kim, D.K. (2022). Estresse oxidativo, integridade gen\u00f4mica e doen\u00e7as hep\u00e1ticas. Mol\u00e9culas, 27.","DOI":"10.3390\/molecules27103159"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1093\/toxsci\/kfu233","article-title":"Molecular mechanisms of acrolein toxicity: Relevance to human disease","volume":"143","author":"Moghe","year":"2015","journal-title":"Toxicol. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.cbi.2015.02.021","article-title":"Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: Role of NFjB\/MAPK pathway","volume":"231","author":"Nafees","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Golubkova, A., Leiva, T., Snyder, K., Schlegel, C., Bonvicino, S.M., Agbaga, M.-P., Brush, R.S., Hansen, J.M., Vitiello, P.F., and Hunter, C.J. (2023). Response of the Glutathione (GSH) Antioxidant Defense System to Oxidative Injury in Necrotizing Enterocolitis. Antioxidants, 12.","DOI":"10.3390\/antiox12071385"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0009-8981(03)00171-2","article-title":"Chronic cold exposure affects the antioxidant defense system in various rat tissues","volume":"333","author":"Kaushik","year":"2003","journal-title":"Clin. Chim. Acta"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"18","DOI":"10.5539\/jfr.v3n3p18","article-title":"Protective effect of hydroethanolic extracts of Solanum scabrum and Cola verticillata against cyclophosphamide induced toxicity in female rats","volume":"3","author":"Angie","year":"2014","journal-title":"J. Food Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s12640-020-00205-0","article-title":"Curcumin Administration Mitigates Cyclophosphamide-Induced Oxidative Damage and Restores Alteration of Enzymes Associated with Cognitive Function in Rats\u2019 Brain","volume":"38","author":"Akomolafe","year":"2020","journal-title":"Neurotox. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.neuro.2023.06.008","article-title":"Neuroprotective effect of quercetin and nano-quercetin against cyclophosphamide-induced oxidative stress in the rat brain: Role of Nrf2\/ HO-1\/Keap-1 signaling pathway","volume":"98","author":"AbdElrazek","year":"2023","journal-title":"Neurotoxicology"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Tan, Q., Yan, X., Chen, L., Jiang, K., and Guo, Z. (2024). Dietary flavonoids protect human brain microvascular endothelial cell from oxidative stress-induced dysfunction. Mol. Cell. Toxicol., 1\u201311.","DOI":"10.1007\/s13273-024-00461-7"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ye, B., Ling, W., Wang, Y., Jaisi, A., and Olatunji, O.J. (2022). Protective Effects of Chrysin against Cyclophosphamide-Induced Cardiotoxicity in Rats: A Biochemical and Histopathological Approach. Chem. Biodivers., 19.","DOI":"10.1002\/cbdv.202100886"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/9\/706\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:51:29Z","timestamp":1760111489000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/9\/706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,8]]},"references-count":70,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["biology13090706"],"URL":"https:\/\/doi.org\/10.3390\/biology13090706","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,8]]}}}