Photobiomodulation in metabolic syndrome: effects on white and brown adipose tissues from mice

A síndrome metabólica (SM) é uma condição clínica que agrupa uma variedade de morbidades, como intolerância à glicose e obesidade. Na obesidade, o tecido adiposo branco (TAB) apresenta características inflamatórias que interferem na ação da insulina, levando à ocorrência de Diabetes do tipo 2. O tecido adiposo marrom (TAM), que tem como principal função a termogênese através da oxidação mitocondrial de cadeias carbônicas, se encontra hiporresponsivo aos estímulos clássicos na SM, como, por exemplo, a exposição ao frio. Estratégias para modular os processos inflamatórios do TAB e ativar o metabolismo do TAM podem atenuar as consequências da SM. Os reconhecidos efeitos anti-inflamatórios e de ativação do metabolismo mitocondrial da fotobiomodulação (PBM) indicam que essa poderia ser uma proposta terapêutica para a SM. Sendo esse o nosso foco de estudo, camundongos adultos, machos, da linhagem C57BL/6 receberam dieta hiperlipídica para indução da SM. Os animais foram então irradiados usando um dispositivo LED sobre a superfície abdominal (λ = 850 nm) ou interescapular (λ = 660 nm) para modular a inflamação do TAB ou ativar o TAM, respectivamente. O tratamento consistiu em 6 sessões de irradiação, distribuídas no decorrer de 21 dias. Apesar de não terem apresentado alterações na massa corporal e Índice de Lee, os animais irradiados na região abdominal (HFABD850) apresentaram 50 % menos células inflamatórias no TAB epididimal e também apresentaram melhora no teste de tolerância à glicose 24 h após a última sessão de tratamento. Nos animais obesos irradiados na região interescapular (HFTAM660), as irradiações promoveram aumento de duas vezes na massa do TAM, além de aumento da temperatura dorsal e da captação de 18F-FDG após exposição a baixas temperaturas. O soro desses animais (HFTAM660) também se mostrou mais semelhante ao de animais eutróficos. Nossos achados indicam que a PBM, nos parâmetros investigados, pode ser aplicada ao tratamento da SM.Metabolic syndrome (MS) is a clinical condition comprising a variety of morbidities, such as glucose intolerance and obesity. The white adipose tissue (WAT) of obese individuals presents inflammatory characteristics that directly impairs insulin response, and may lead to the development of type 2 diabetes. Brown adipose tissue (BAT), whose main function is thermogenesis through mitochondrial oxidation of carbon chains, is also altered in SM. In obese individuals, this tissue is hyporesponsive to classical stimuli such as cold exposure. Strategies modulating the inflammatory processes within WAT and activating the metabolism of BAT can therefore attenuate the consequences of the SM. The recognized anti-inflammatory effects and the activation of mitochondrial metabolism of photobiomodulation (PBM) allow us to suppose that this could be an interesting therapeutic proposal for MS. As this was our study focus, adult male C57BL/6 mice received a high-fat diet to induce MS. The animals were then irradiated using an LED device on the abdominal (λ = 850 nm) or interscapular (λ = 660 nm) surfaces to modulate WAT inflammation or activate BAT, respectively. The treatment consisted of 6 irradiation sessions, distributed over 21 days. Although no changes in body mass and Lee index were observed, animals irradiated in the abdominal region (HFABD850) showed 50% fewer inflammatory cells in the epididymal TAB and also presented improvement in glucose tolerance test 24 h after the last treatment session. In obese animals irradiated in the interscapular region (HFTAM660), the treatment promoted a two-fold increase in BAT mass, as well as an increase in dorsal temperature and 18F-FDG uptake after exposure to cold temperatures. The serum of these animals (HFTAM660) was also more similar to that of eutrophic animals. Our findings indicate that PBM, in the investigated parameters, can be applied to the treatment of MS

Low level light therapy as a therapeutic proposal for mice with metabolic syndrome

A síndrome metabólica (SM) é uma condição clínica que agrupa uma variedade de morbidades, como hiperglicemia, pressão arterial elevada, dislipidemia aterogênica e obesidade (particularmente na região abdominal). Nessa conjuntura, os principais tecidos-alvo da ação da insulina sofrem alterações metabólicas que aumentam o risco de ocorrência de doenças cardiovasculares e diabetes tipo 2. As alterações teciduais observadas são caracterizadas por infiltrados de células do sistema imune, especialmente macrófagos. Citocinas pró-inflamatórias, como TNF-α, são liberadas e alcançam a corrente sanguínea, promovendo nesses indivíduos um estado de inflamação crônica e sistêmica. O tecido adiposo intra-abdominal parece ser de particular importância no estabelecimento desse quadro inflamatório, e estratégias direcionadas no sentido de modular os processos inflamatórios nesse tecido podem atenuar as consequências da SM. Os reconhecidos benefícios da terapia com luz de baixa potência em condições inflamatórias nos permitem supor que essa poderia ser uma proposta terapêutica para a SM. Sendo esse o nosso foco de estudo, camundongos adultos, machos, das linhagens C57BL/6 e BALB/c receberam dieta hiperlipídica durante 8 semanas para indução do quadro de SM. Os animais foram então irradiados sobre a superfície abdominal no decorrer de 21 dias, usando um LED (λ = 850 nm, 6 sessões, 300 s por sessão, potência = 60 mW, fluência = 6 J/cm², taxa de fluência = 19 mW/cm²). Antes e durante o tratamento, amostras de sague foram coletadas para quantificação de glicose, colesterol total e triglicérides plasmáticos. Considerando os parâmetros de irradiação adotados, a terapia com luz de baixa potência não se mostrou efetiva para alterar massa corporal, glicemia, colesterol total e triglicérides de camundongos alimentados com dieta hiperlipídica.Metabolic syndrome comprises a constellation of morbidities such as insulin resistance, hyperinsulinemia, atherogenic dyslipidemia, dysglycemia and obesity (especially abdominal). Metabolic alterations are observed in major insulin target organs, increasing the risk of cardiovascular diseases, type-2 diabetes and therefore mortality. Tissue alterations are characterized by immune cells infiltrates (especially activated macrophages). Released inflammatory mediators such as TNF-α induce chronic inflammation in subjects with metabolic syndrome, since inflammatory pathways are activated in the neighboring cells. The intra-abdominal adipose tissue appears to be of particular importance in the onset of the inflammatory state, and strategies contributing to modulate the inflammatory process within this adipose tissue can mitigate the metabolic syndrome consequences. Considering the low level light therapy (LLLT) recognized benefits in inflammatory conditions, we hypothesized this therapeutic approach could promote positive effects in modulating the inflammatory state of metabolic syndrome. That being the scope of this study, male C57BL/6 AND BALB/c mice were submitted to a high-fat/high-fructose diet among 8 weeks to induce metabolic syndrome. Animals were then irradiated on the abdominal region during 21 days using an 850 nm LED (6 sessions, 300 seconds per session, 60 mW output power, ~6 J/cm² fluence, ~19 mW/cm² fluence rate). Before and during treatment, blood was sampled either from the retro-orbital plexus or from tail puncture for glucose, total cholesterol and triglycerides analysis. Our results indicate no alterations on these metabolic parameters after LLLT

Inhomogeneity in optical properties of rat brain: a study for LLLT dosimetry

Over the last few years, low-level light therapy (LLLT) has shown an incredible suitability for a wide\ud range of applications for central nervous system (CNS) related diseases. In this therapeutic modality light\ud dosimetry is extremely critical so the study of light propagation through the CNS organs is of great\ud importance. To better understand how light intensity is delivered to the most relevant neural sites we\ud evaluated optical transmission through slices of rat brain point by point. We experimented red\ud (λ = 660 nm) and near infrared (λ = 808 nm) diode laser light analyzing the light penetration and\ud distribution in the whole brain. A fresh Wistar rat (Rattus novergicus) brain was cut in sagittal slices and\ud illuminated with a broad light beam. A high-resolution digital camera was employed to acquire data of\ud transmitted light. Spatial profiles of the light transmitted through the sample were obtained from the\ud images. Peaks and valleys in the profiles show sites where light was less or more attenuated. The peak\ud intensities provide information about total attenuation and the peak widths are correlated to the scattering\ud coefficient at that individual portion of the sample. The outcomes of this study provide remarkable\ud information for LLLT dose-dependent studies involving CNS and highlight the importance of LLLT\ud dosimetry in CNS organs for large range of applications in animal and human diseases.CNP

Type I and Type II Photosensitized Oxidation Reactions : Guidelines and Mechanistic Pathways.

Here, 10 guidelines are presented for a standardized definition of type I and type II photosensitized oxidation reactions. Because of varied notions of reactions mediated by photosensitizers, a checklist of recommendations is provided for their definitions. Type I and type II photoreactions are oxygendependent and involve unstable species such as the initial formation of radical cation or neutral radicals from the substrates and/or singlet oxygen (1O2 1Δg) by energy transfer to molecular oxygen. In addition, superoxide anion radical (O2←) can be generated by a charge-transfer reaction involving O2 or more likely indirectly as the result of O2-mediated oxidation of the radical anion of type I photosensitizers. In subsequent reactions, O2← may add and/or reduce a few highly oxidizing radicals that arise from the deprotonation of the radical cations of key biological targets. O2← can also undergo dismutation into H2O2, the precursor of the highly reactive hydroxyl radical (OH) that may induce delayed oxidation reactions in cells. In the second part, several examples of type I and type II photosensitized oxidation reactions are provided to illustrate the complexity and the diversity of the degradation pathways of mostly relevant biomolecules upon one-electron oxidation and singlet oxygen reactions.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Type I and Type II Photosensitized Oxidation Reactions: Guidelines and Mechanistic Pathways

Here, 10 guidelines are presented for a standardized definition of type I and type II photosensitized oxidation reactions. Because of varied notions of reactions mediated by photosensitizers, a checklist of recommendations is provided for their definitions. Type I and type II photoreactions are oxygen-dependent and involve unstable species such as the initial formation of radical cation or neutral radicals from the substrates and/or singlet oxygen (1O2 1∆g) by energy transfer to molecular oxygen. In addition, superoxide anion radical (O.- 2) can be generated by a charge-transfer reaction involving O2 or more likely indirectly as the result of O2-mediated oxidation of the radical anion of type I photosensitizers. In subsequent reactions, O.- 2 may add and/or reduce a few highly oxidizing radicals that arise from the deprotonation of the radical cations of key biological targets.O.- 2 can also undergo dismutation into H2O2, the precursor of the highly reactive hydroxyl radical (.OH) that may induce delayed oxidation reactions in cells. In the second part, several examples of type I and type II photosensitized oxidation reactions are provided to illustrate the complexity and the diversity of the degradation pathways of mostly relevant biomolecules upon one-electron oxidation and singlet oxygen reactions.Fil: Baptista, Maurício S.. Universidade de Sao Paulo; BrasilFil: Cadet, Jean. University of Sherbrooke; CanadáFil: Di Mascio, Paolo. Universidade de Sao Paulo; BrasilFil: Ghogare, Ashwini A.. Brooklyn College; Estados Unidos. City University of New York; Estados UnidosFil: Greer, Alexander. Brooklyn College; Estados Unidos. City University of New York; Estados UnidosFil: Hamblin, Michael R.. Massachusetts General Hospital; Estados Unidos. Harvard Medical School; Estados UnidosFil: Lorente, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Nunez, Silvia Cristina. Universidade Camilo Castelo Branco; BrasilFil: Simoes Ribeiro, Martha. Comissao Nacional de Energia Nuclear. Centro de Lasers e Aplicacoes. Instituto de Pesquisas Energeticas e Nucleares.; BrasilFil: Thomas, Andrés Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Vignoni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Yoshimura, Tania Mateus. Comissao Nacional de Energia Nuclear. Centro de Lasers e Aplicacoes. Instituto de Pesquisas Energeticas e Nucleares.; Brasi