Citrus flavanone metabolites protect pancreatic-beta cells under oxidative stress induced by cholesterol

Autor(es)

Anacleto, Sara L. ^{[1, 2]} ; Milenkovic, Dragan ^{[3, 4]} ; Kroon, Paul A. ^[5] ; Needs, Paul W. ^[5] ; Lajolo, Franco Maria ^{[1, 2]} ; Hassimotto, Neuza M. A. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Food Res Ctr FoRC CEPID, Av Prof Lineu Prestes 580, Bloco 14, BR-05508900 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Dept Food Sci & Nutr, Sch Pharmaceut Sci, Av Prof Lineu Prestes 580, Bloco 14, BR-05508900 Sao Paulo, SP - Brazil

^[3] Univ Calif Davis, Dept Internal Med, Div Cardiovasc Med, 451 East Hlth Sci Dr, Davis, CA 95616 - USA

^[4] Univ Auvergne, Unite Nutr Humaine, Clermont Univ, INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Ferrand - France

^[5] Norwich Res Pk, Quadram Inst Biosci, Norwich, Norfolk - England

• Tipo de documento: Artigo Científico
• Fonte: FOOD & FUNCTION; v. 11, n. 10, p. 8612-8624, OCT 1 2020.
• Citações Web of Science: 0

Resumo

Cholesterol is one of the triggers of oxidative stress in the pancreatic-beta cell, generating high levels of reactive oxygen species, which leads to impairment of insulin synthesis and secretion. Bioactive compounds, such as citrus flavanones, which possess anti-inflammatory and antioxidant activities, could reduce oxidative stress in beta-cells and improve their function. We describe for the first time the protective effects of the phase-II flavanone metabolites {[}naringenin 7-O-glucuronide, hesperetin 3 `-O-glucuronide, and hesperetin 7-O-glucuronide], and two flavanones-catabolites derived from gut microbiota metabolism {[}hippuric acid and 3-(4-hydroxyphenyl)propionic acid], on pancreatic beta-cell line MIN6 under oxidative stress, at physiologically relevant concentration. Cholesterol reduced cell viability in a dose and time-dependent manner, with an improvement in the presence of the metabolites. Moreover, flavanone metabolites attenuated oxidative stress by reducing levels of lipid peroxides, superoxide anions, and hydrogen peroxide. In response to the reduction of reactive oxygen species, a decrease in superoxide dismutase and glutathione peroxidase activities was observed; these activities were elevated by cholesterol. Moreover, all the flavanone metabolites improved mitochondrial function and insulin secretion, and reduced apoptosis. Flavanone metabolites were found uptake by beta-cells, and therefore could be responsible for the observed protective effects. These results demonstrated that circulating phase-II hesperetin and naringenin metabolites, and also phenolics derived from gut microbiota, protect pancreatic-beta cells against oxidative stress, leading to an improvement in beta-cell function and could be the bioactive molecules derived from the citrus consumption. (AU)

• Processo FAPESP: 13/07914-8 - FoRC - Centro de Pesquisa em Alimentos
• Beneficiário: Bernadette Dora Gombossy de Melo Franco
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 18/03965-0 - Flavanonas de Citrus- mecanismos de proteção de células beta-pancreáticas submetidas ao estresse oxidativo
• Beneficiário: Sara Lima Anacleto
• Modalidade de apoio: Bolsas no Brasil - Mestrado