{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T01:04:45Z","timestamp":1778029485021,"version":"3.51.4"},"reference-count":65,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"FAPESP-Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/03381-9"],"award-info":[{"award-number":["2018\/03381-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP-Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/15954-9"],"award-info":[{"award-number":["2022\/15954-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP-Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["407201\/2021-1"],"award-info":[{"award-number":["407201\/2021-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP-Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["309180\/2021-0"],"award-info":[{"award-number":["309180\/2021-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq\u2013Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["2018\/03381-9"],"award-info":[{"award-number":["2018\/03381-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq\u2013Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["2022\/15954-9"],"award-info":[{"award-number":["2022\/15954-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq\u2013Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["407201\/2021-1"],"award-info":[{"award-number":["407201\/2021-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq\u2013Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["309180\/2021-0"],"award-info":[{"award-number":["309180\/2021-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Cardiovascular disease is a leading cause of death worldwide. Heart failure is a cardiovascular disease with high prevalence, morbidity, and mortality. Several natural compounds have been studied for attenuating pathological cardiac remodeling. Orange juice has been associated with cardiovascular disease prevention by attenuating oxidative stress. However, most studies have evaluated isolated phytochemicals rather than whole orange juice and usually under pathological conditions. In this study, we evaluated plasma metabolomics in healthy rats receiving Pera or Moro orange juice to identify possible metabolic pathways and their effects on the heart. Methods: Sixty male Wistar rats were allocated into 3 groups: control (C), Pera orange juice (PO), and Moro orange juice (MO). PO and MO groups received Pera orange juice or Moro orange juice, respectively, and C received water with maltodextrin (100 g\/L). Echocardiogram and euthanasia were performed after 4 weeks. Plasma metabolomic analysis was performed by high-resolution mass spectrometry. Type I collagen was evaluated in picrosirius red-stained slides and matrix metalloproteinase (MMP)-2 activity by zymography. MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-4, type I collagen, and TNF-\u03b1 protein expression were evaluated by Western blotting. Results: We differentially identified three metabolites in PO (N-docosahexaenoyl-phenylalanine, diglyceride, and phosphatidylethanolamine) and six in MO (N-formylmaleamic acid, N2-acetyl-L-ornithine, casegravol isovalerate, abscisic alcohol 11-glucoside, cyclic phosphatidic acid, and torvoside C), compared to controls, which are recognized for their possible roles in cardiac remodeling, such as extracellular matrix regulation, inflammation, oxidative stress, and membrane integrity. Cardiac function, collagen level, MMP-2 activity, and MMP-9, TIMP-2, TIMP-4, type I collagen, and TNF-\u03b1 protein expression did not differ between groups. Conclusion: Ingestion of Pera and Moro orange juice induces changes in plasma metabolites related to the regulation of extracellular matrix, inflammation, oxidative stress, and membrane integrity in healthy rats. Moro orange juice induces a larger number of differentially expressed metabolites than Pera orange juice. Alterations in plasma metabolomics induced by both orange juice are not associated with modifications in cardiac extracellular matrix components. Our results allow us to postulate that orange juice may have beneficial effects on pathological cardiac remodeling.<\/jats:p>","DOI":"10.3390\/metabo13080902","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T11:24:26Z","timestamp":1690975466000},"page":"902","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effects of Pera Orange Juice and Moro Orange Juice in Healthy Rats: A Metabolomic Approach"],"prefix":"10.3390","volume":"13","author":[{"given":"Anderson S. S.","family":"Fujimori","sequence":"first","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana P. D.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9023-5756","authenticated-orcid":false,"given":"Amanda G.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fl\u00e1via L.","family":"Dias-Audibert","sequence":"additional","affiliation":[{"name":"Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas 13083-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2079-8588","authenticated-orcid":false,"given":"Carolina R.","family":"Tonon","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1159-5030","authenticated-orcid":false,"given":"Priscila P.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Dantas","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silmeia G.","family":"Zanati","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo R.","family":"Catharino","sequence":"additional","affiliation":[{"name":"Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas 13083-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo A. M.","family":"Zornoff","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula S.","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio A. R.","family":"de Paiva","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7728-4505","authenticated-orcid":false,"given":"Marina P.","family":"Okoshi","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0479-0364","authenticated-orcid":false,"given":"Estela O.","family":"Lima","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2875-9532","authenticated-orcid":false,"given":"Bertha F.","family":"Polegato","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1161\/CIR.0000000000001123","article-title":"Heart disease and stroke statistics\u20142023 update: A report from the American Heart Association","volume":"147","author":"Tsao","year":"2023","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.12998\/wjcc.v9.i8.1761","article-title":"Cardiac rehabilitation and its essential role in the secondary prevention of cardiovascular diseases","volume":"9","author":"Winnige","year":"2021","journal-title":"World J. 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