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1.
J Nutr ; 151(4): 810-819, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33561210

RESUMO

BACKGROUND: Sustained fuel excess triggers low-grade inflammation that can drive mitochondrial dysfunction, a pivotal defect in the pathogenesis of insulin resistance in skeletal muscle. OBJECTIVES: This study aimed to investigate whether inflammation in skeletal muscle can be prevented by EPA, and if this is associated with an improvement in mitochondrial fusion, membrane potential, and insulin signaling. METHODS: Human primary myotubes were treated for 24 h with palmitic acid (PA, 500 µM) under hyperglycemic conditions (13 mM glucose), which represents nutrient overload, and in the presence or absence of EPA (100 µM). After the treatments, the expression of peroxisome proliferator-activated receptor γ coactivator 1-α (PPARGC1A) and IL6 was assessed by q-PCR. Western blot was used to measure the abundance of the inhibitor of NF-κB (IKBA), mitofusin-2 (MFN2), mitochondrial electron transport chain complex proteins, and insulin-dependent AKT (Ser473) and AKT substrate 160 (AS 160; Thr642) phosphorylation. Mitochondrial dynamics and membrane potential were evaluated using immunocytochemistry and the JC-1 (tetraethylbenzimidazolylcarbocyanine iodide) dye, respectively. Data were analyzed using 1-factor ANOVA followed by Tukey post hoc test. RESULTS: Nutrient excess activated the proinflammatory NFκB signaling marked by a decrease in IKBA (40%; P < 0.05) and the upregulation of IL6 mRNA (12-fold; P < 0.001). It also promoted mitochondrial fragmentation (53%; P < 0.001). All these effects were counteracted by EPA. Furthermore, nutrient overload-induced drop in mitochondrial membrane potential (6%; P < 0.05) was prevented by EPA. Finally, EPA inhibited fuel surplus-induced impairment in insulin-mediated phosphorylation of AKT (235%; P < 0.01) and AS160 (49%; P < 0.05). CONCLUSIONS: EPA inhibited NFκB signaling, which was associated with an attenuation of the deleterious effects of PA and hyperglycemia on both mitochondrial health and insulin signaling in human primary myotubes. Thus, EPA might preserve skeletal muscle metabolic health during sustained fuel excess but this requires confirmation in human clinical trials.


Assuntos
Ácido Eicosapentaenoico/farmacologia , Inflamação/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Células Cultivadas , Glucose/metabolismo , Humanos , Inflamação/prevenção & controle , Insulina/metabolismo , Resistência à Insulina , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , NF-kappa B/metabolismo , Ácido Palmítico/farmacologia , Transdução de Sinais/efeitos dos fármacos
2.
Eur J Nutr ; 60(3): 1375-1388, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32712699

RESUMO

PURPOSE: The metabolic benefits of the Mediterranean diet have been largely attributed to its olive oil content. Whether the ingested fat amount is relevant to these effects is not clear. We thus compared the effects of high-fat and normal-fat intake of extra-virgin olive oil (EVOO) on the liver proteome. METHODS: Three groups of mice were fed for 12 weeks with either normal-fat diets containing either soybean oil (control, C) or EVOO (NO) or a high-fat EVOO diet (HO). Body weight and food intake were measured weekly and serum parameters were analyzed. The liver was processed for data-independent acquisition mass spectrometry-based proteomics. The differentially expressed proteins among the groups were submitted to pathway enrichment analysis. RESULTS: The consumption of HO diet reduced food intake and serum triglycerides, while it preserved body weight gain, adiposity, and glycemia. However, it increased serum cholesterol and liver mass. The proteomic analysis showed 98 altered proteins, which were allocated in 27 significantly enriched pathways. The pathway analysis suggested stimulation of mitochondrial and peroxissomal ß-oxidation, and inhibition of lipid synthesis and gluconeogenesis in the HO group. Although the NO group failed to show significant liver proteome alterations, it presented reduced body fat, body weight gain, and serum triglycerides and glucose levels. CONCLUSION: The data indicate that the intake of the HO diet induced hepatic adjustments, which were partially successful in counteracting the detrimental outcomes of a high-fat feeding. Contrastingly, the NO diet had beneficial effects which were not accompanied by significant modifications on hepatic proteome.


Assuntos
Proteoma , Proteômica , Animais , Dieta Hiperlipídica/efeitos adversos , Fígado , Camundongos , Azeite de Oliva
3.
Nutr Metab Cardiovasc Dis ; 31(3): 717-732, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33558092

RESUMO

The year 2020 celebrated the tenth anniversary of the recognition of the Mediterranean Diet as Intangible Cultural Heritage of Humanity by the UNESCO Intergovernmental Committee. This event represented a milestone in the history of nutrition, as the Mediterranean diet was the first traditional food practice to receive such award. Since then, a lot has been discussed not only on the beneficial aspects of the Mediterranean diet, but also on its complex role as a lifestyle model that includes a set of skills, knowledge and intercultural dialogue. This process ended up with the recognition in 2019 of Mediterranean diet as a possibly universal model of healthy diet from the EAT-Lancet Commission. These concepts were widely debated at the 2019 "Ancel Keys" International Seminar, held in Ascea (Italy) (for more information see: www.mediterraneandietseminar.org) with the aim to stimulate interest and awareness of a young group of participants on the current problems inherent to the effective implementation of the Mediterranean diet. The present article collects the contributions of several lecturers at the Seminar on key issues such as methodological and experimental approach, sustainability, molecular aspects in disease prevention, future exploitation, without neglecting a historical view of the Seven Countries Study. From the Seminar conclusions emerged a still vibrant and modern role of Mediterranean diet. The years to come will see national and international efforts to reduce the barriers that limit adherence to Mediterranean diet in order to plan for multi-factorial and targeted interventions that would guide our populations to a sustainable healthy living.


Assuntos
Doença Crônica/prevenção & controle , Dieta Saudável , Dieta Mediterrânea , Medicina Baseada em Evidências , Comportamento de Redução do Risco , Animais , Doença Crônica/epidemiologia , Humanos , Estado Nutricional , Valor Nutritivo , Fatores de Proteção , Medição de Risco , Fatores de Risco
4.
Ecotoxicol Environ Saf ; 208: 111475, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33068975

RESUMO

Cocaine is one of the most widely used illicit drugs in the world, and as a result of incomplete removal by sewage treatment plants it is found in surface waters, where it represents a new potential risk for aquatic organisms. In this study we evaluated the influence of environmental concentrations of cocaine on the liver and the kidney of the European eel (Anguilla anguilla). The eels were exposed to 20 ng L-1 of cocaine for fifty days, after which, three and ten days after the interruption of cocaine exposure their livers and kidneys were compared to controls. The general morphology of the two organs was evaluated, as well as the following parameters: cytochrome oxidase (COX) and caspase-3 activities, as markers of oxidative metabolism and apoptosis activation, respectively; glucose-regulated protein (GRP)78 levels, as a marker of endoplasmic reticulum (ER)-stress; blood glucose level, as stress marker; serum levels of alanine aminotransferase (ALT), as a marker of liver injury and serum levels of C-reactive protein (CRP), as a marker of the inflammatory process. The liver showed morphologic alterations such as necrotic areas, karyolysis and pyknotic nuclei, while the kidneys had dilated glomeruli and the renal tubules showed pyknotic nuclei and karyolysis. In the kidney, the alterations persisted after the interruption of cocaine exposure. In the liver, COX and caspase-3 activities increased (COX: P = 0.01; caspase-3: P = 0.032); ten days after the interruption of cocaine exposure, COX activity returned to control levels (P = 0.06) whereas caspase-3 activity decreased further (P = 0.012); GRP78 expression increased only in post-exposure recovery specimens (three days: P = 0.007 and ten days: P = 0.008 after the interruption of cocaine exposure, respectively). In the kidney, COX and caspase-3 activities increased (COX: P = 0.02; caspase-3: P = 0.019); after the interruption of cocaine exposure, COX activity remained high (three days: P = 0.02 and ten days: P = 0.029 after the interruption of cocaine exposure, respectively) whereas caspase-3 activity returned to control values (three days: P = 0.69 and ten days: P = 0.67 after the interruption of cocaine exposure, respectively). Blood glucose and serum ALT and CRP levels increased (blood glucose: P = 0.01; ALT: P = 0.001; CRP: 0.015) and remained high also ten days after the interruption of cocaine exposure (blood glucose: P = 0.009; ALT: P = 0.0031; CRP: 0.036). These results suggest that environmental cocaine concentrations adversely affected liver and kidney of this species.


Assuntos
Anguilla/fisiologia , Cocaína/toxicidade , Poluentes Químicos da Água/toxicidade , Alanina Transaminase/metabolismo , Anguilla/sangue , Animais , Glicemia , Proteína C-Reativa/metabolismo , Caspase 3/metabolismo , Cocaína/análise , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Drogas Ilícitas , Rim/metabolismo , Fígado/metabolismo
5.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575980

RESUMO

Mitochondrial impairments in dynamic behavior (fusion/fission balance) associated with mitochondrial dysfunction play a key role in cell lipotoxicity and lipid-induced metabolic diseases. The present work aimed to evaluate dose- and time-dependent effects of the monounsaturated fatty acid oleate on mitochondrial fusion/fission proteins in comparison with the saturated fatty acid palmitate in hepatic cells. To this end, HepG-2 cells were treated with 0, 10 µM, 50 µM, 100 µM, 250 µM or 500 µM of either oleate or palmitate for 8 or 24 h. Cell viability and lipid accumulation were evaluated to assess lipotoxicity. Mitochondrial markers of fusion (mitofusin 2, MFN2) and fission (dynamin-related protein 1, DRP1) processes were evaluated by Western blot analysis. After 8 h, the highest dose of oleate induced a decrease in DRP1 content without changes in MFN2 content in association with cell viability maintenance, whereas palmitate induced a decrease in cell viability associated with a decrease mainly in MFN2 content. After 24 h, oleate induced MFN2 increase, whereas palmitate induced DRP1 increase associated with a higher decrease in cell viability with high doses compared to oleate. This finding could be useful to understand the role of mitochondria in the protective effects of oleate as a bioactive compound.


Assuntos
Dinaminas/genética , GTP Fosfo-Hidrolases/genética , Doenças Metabólicas/genética , Dinâmica Mitocondrial/efeitos dos fármacos , Proteínas Mitocondriais/genética , Ácido Oleico/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ácidos Graxos Monoinsaturados/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/toxicidade , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/patologia , Dinâmica Mitocondrial/genética , Ácido Oleico/farmacologia , Palmitatos/metabolismo , Palmitatos/farmacologia
6.
Int J Mol Sci ; 21(5)2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32164371

RESUMO

The growing number of studies on metallothioneins (MTs), cysteine-rich metal-binding proteins, have been disclosing new functions of these proteins. Thanks to their inducibility, they were considered to play a pivotal role in regulating trace metals homeostasis and in detoxification from heavy metals; nowadays, it is known that they are involved in various physiological and pathological processes, such as regulation of apoptosis, elimination of free radicals, and protection of nucleic acids against toxic insults. MT induction has been demonstrated following stress factors other than heavy metals, such as endocrine-disrupting chemicals, insecticides, and herbicides. However, retrieved data are often controversial: in some cases, xenobiotics elicit MT expression and synthesis; under different conditions, they lead to a decrease in cellular MT content. This review describes the MT response to dichlorodiphenyltrichloroethane (DDT) contamination in mammalian tissues. In particular, attention focuses on changes in MT expression, synthesis, and localization in rat liver, kidneys, and testes following oral administration of dichlorodiphenyldichloroethylene (DDE), the main metabolite of DDT, under normal dietary conditions or in combination with a high fat diet potentially able to increase the cellular uptake of this lipophilic pesticide. The potential connection between MT expression and synthesis, lipophilic substances and trace metals availability is also discussed.


Assuntos
Diclorodifenil Dicloroetileno/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Metalotioneína/genética , Metalotioneína/metabolismo , Administração Oral , Animais , Diclorodifenil Dicloroetileno/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Ratos
7.
Environ Toxicol ; 34(3): 283-293, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30575243

RESUMO

Metallothionein is well known for its detoxificant and anti-oxidant properties and has been shown to be effective to prevent hydroxyl radical-generated DNA degradation. The purpose of this investigation was to analyze the combined effect of two factors promoting cellular oxidative-stress, that is, the administration of the pesticide dichloro-diphenyl-dichloroethylene (DDE) and a high fat diet, on metallothionein expression and synthesis in rat liver and kidney. DDE is the main metabolite of dichloro-diphenyl-trichloroethane (DDT), and is commonly found in the food chain and in all tissues of living organisms, carried by the fats. Male Wistar rats were fed with a standard (N) or a high fat (HF) diet and exposed to DDE (10 mg/kg body mass, N + DDE and HF + DDE groups) or vehicle (corn oil, N, and HF groups) via gavage every day for 28 days. Tissues histology was determined by light microscopy analysis; differences in metallothionein gene expression and synthesis by real-time PCR and western blot, respectively. Finally, protein cellular localization was established by immunocytochemistry. The results showed a different involvement of metallothionein in defending tissues from HF- and DDE-induced oxidative stress, suggesting that hepatic and renal cells use different strategies against pro-oxidant species. In both cell types a marked increase in the metallothionein content was observed in the nucleus, with a concomitant drop of the cytoplasmatic protein, either under HF- and DDE-stress conditions; however, no synergistic or additive effects were observed between the action of fats and pesticide. These findings reinforce the role of metallothionein in protecting DNA from oxidative damage.


Assuntos
Diclorodifenil Dicloroetileno/toxicidade , Dieta Hiperlipídica/efeitos adversos , Metalotioneína/biossíntese , Metalotioneína/genética , Praguicidas/toxicidade , Animais , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
8.
Int J Mol Sci ; 20(12)2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31242698

RESUMO

High-fat diets rich in fish oil (HFO diet, mainly ω3-PUFAs), in contrast to high-fat diets rich in lard (HL diet, mainly saturated fatty acids) have been shown to induce improvement in mitochondrial function and fusion processes associated with a reduction in reactive oxygen species production in both liver and skeletal muscle. High-fat diets may also impair testicular function, and mitochondria represent important cellular organelles with a pivotal role in reproductive function. Mitochondria are dynamic organelles that frequently undergo fission/fusion processes. A shift toward mitochondrial fusion process has been associated with improvement of mitochondrial function, as well as with ω3-PUFAs protective effects. The present study aimed to analyze the effect of chronic overfeeding (six weeks) with HFO or HL diet on testicular tissue histology, oxidative stress, antioxidant defenses, and mitochondrial fusion (mitofusin 2) and fission (dynamic related protein 1) protein. Our results showed that HFO diet induced less testicular histology impairment, oxidative stress, and apoptosis compared to a HL diet. This finding was associated with an increase in antioxidant activities and a shift toward mitochondrial fusion processes induced by HFO diet compared to HL diet, suggesting that ω3-PUFAs may act as bioactive compound targeting mitochondria dynamics to prevent testicular impairment.


Assuntos
Antioxidantes/farmacologia , Dieta Hiperlipídica , Óleos de Peixe , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Testículo/metabolismo , Animais , Apoptose/efeitos dos fármacos , Peso Corporal , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Tamanho do Órgão , Estresse Oxidativo/efeitos dos fármacos , Ratos , Testículo/efeitos dos fármacos
9.
Int J Mol Sci ; 15(2): 3040-63, 2014 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-24562331

RESUMO

Dietary fat sources may differentially affect the development of inflammation in insulin-sensitive tissues during chronic overfeeding. Considering the anti-inflammatory properties of ω-3 fatty acids, this study aimed to compare the effects of chronic high-fish oil and high-lard diets on obesity-related inflammation by evaluating serum and tissue adipokine levels and histological features in insulin-sensitive tissues (white adipose tissue, skeletal muscle and liver). As expected, a high-lard diet induced systemic and peripheral inflammation and insulin resistance. Conversely, compared with a high-lard diet, a high-fish oil diet resulted in a lower degree of systemic inflammation and insulin resistance that were associated with a lower adipocyte diameter as well as lower immunoreactivity for transforming growth factor ß 1 (TGFß1) in white adipose tissue. A high-fish oil diet also resulted in a lower ectopic lipid depot, inflammation degree and insulin resistance in the skeletal muscle and liver. Moreover, a high-fish oil diet attenuated hepatic stellate cell activation and fibrogenesis in the liver, as indicated by the smooth muscle α-actin (α-SMA) and TGFß1 levels. The replacement of lard (saturated fatty acids) with fish oil (ω-3 fatty acids) in chronic high-fat feeding attenuated the development of systemic and tissue inflammation.


Assuntos
Dieta Hiperlipídica , Gorduras Insaturadas na Dieta , Actinas/metabolismo , Adipocinas/sangue , Adiponectina/sangue , Tecido Adiposo Branco/citologia , Tecido Adiposo Branco/metabolismo , Animais , Glicemia/análise , Quimiocina CCL2/sangue , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/patologia , Imuno-Histoquímica , Insulina/sangue , Leptina/sangue , Fígado/patologia , Masculino , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologia , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
10.
Nutrients ; 16(16)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39203754

RESUMO

Brown adipose tissue (BAT) participates in thermogenesis and energy homeostasis. Studies on factors capable of influencing BAT function, such as a high-fat diet (HFD) or exposure to environmental pollutants, could be useful for finding metabolic targets for maintaining energy homeostasis. We evaluated the effect of chronic exposure to dichlorodiphenyldichloroethylene (DDE), the major metabolite of dichlorodiphenyltrichloroethane (DDT), and/or a HFD on BAT morphology, mitochondrial mass, dynamics, and oxidative stress in rats. To this end, male Wistar rats were treated for 4 weeks with a standard diet, or a HFD alone, or together with DDE. An increase in paucilocular adipocytes and the lipid droplet size were observed in HFD-treated rats, which was associated with a reduction in mitochondrial mass and in mitochondrial fragmentation, as well as with increased oxidative stress and upregulation of the superoxide dismutase-2. DDE administration mimics most of the effects induced by a HFD on BAT, and it aggravates the increase in the lipid droplet size when administered together with a HFD. Considering the known role of oxidative stress in altering BAT functionality, it could underlie the ability of both DDE and a HFD to induce similar metabolic adaptations in BAT, leading to reduced tissue thermogenesis, which can result in a predisposition to the onset of energy homeostasis disorders.


Assuntos
Tecido Adiposo Marrom , Diclorodifenil Dicloroetileno , Dieta Hiperlipídica , Poluentes Ambientais , Estresse Oxidativo , Ratos Wistar , Animais , Masculino , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Dieta Hiperlipídica/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Ratos , Diclorodifenil Dicloroetileno/toxicidade , Superóxido Dismutase/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Adaptação Fisiológica/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Termogênese/efeitos dos fármacos , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/efeitos dos fármacos
11.
ACS Appl Mater Interfaces ; 15(3): 3882-3893, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36629473

RESUMO

The catalytic and antioxidant properties of platinum nanoparticles (PtNPs) make them promising candidates for several applications in nanomedicine. However, an open issue, still shared among most nanomaterials, is the understanding on how internalized PtNPs, which are confined within endo-lysosomal compartments, can exert their activities. To address this problem, here we study the protective effect of 5 nm PtNPs on a human hepatic (HepG2) cell line exposed to dichlorodiphenylethylene (DDE) as a model of oxidative stress. Our results indicate that PtNPs are very efficient to reduce DDE-induced damage in HepG2 cells, in an extent that depends on DDE dose. PtNPs can contrast the unbalance of mitochondrial dynamics induced by DDE and increase the expression of the SOD2 mitochondrial enzyme that recovers cells from oxidative stress. Interestingly, in cells treated with PtNPs─alone or in combination with DDE─mitochondria form contact sites with a rough endoplasmic reticulum and endo-lysosomes containing nanoparticles. These findings indicate that the protective capability of PtNPs, through their intrinsic antioxidant properties and modulating mitochondrial functionality, is mediated by an inter-organelle crosstalk. This study sheds new light about the protective action mechanisms of PtNPs and discloses a novel nano-biointeraction mechanism at the intracellular level, modulated by inter-organelle communication and signaling.


Assuntos
Antioxidantes , Nanopartículas Metálicas , Humanos , Antioxidantes/farmacologia , Platina/farmacologia , Transdução de Sinais , Mitocôndrias/metabolismo
12.
Antioxidants (Basel) ; 12(7)2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37508009

RESUMO

Ketone bodies (KBs) are an alternative energy source under starvation and play multiple roles as signaling molecules regulating energy and metabolic homeostasis. The mechanism by which KBs influence visceral white adipose tissue physiology is only partially known, and our study aimed to shed light on the effects they exert on such tissue. To this aim, we administered 1,3-butanediol (BD) to rats since it rapidly enhances ß-hydroxybutyrate serum levels, and we evaluated the effect it induces within 3 h or after 14 days of treatment. After 14 days of treatment, rats showed a decrease in body weight gain, energy intake, gonadal-WAT (gWAT) weight, and adipocyte size compared to the control. BD exerted a pronounced antioxidant effect and directed redox homeostasis toward reductive stress, already evident within 3 h after its administration. BD lowered tissue ROS levels and oxidative damage to lipids and proteins and enhanced tissue soluble and enzymatic antioxidant capacity as well as nuclear erythroid factor-2 protein levels. BD also reduced specific mitochondrial maximal oxidative capacity and induced endoplasmic reticulum stress as well as interrelated processes, leading to changes in the level of adipokines/cytokines involved in inflammation, macrophage infiltration into gWAT, adipocyte differentiation, and lipolysis.

13.
Environ Toxicol Pharmacol ; 87: 103684, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34052433

RESUMO

1,1,1-trichloro-2,2-bis (p-chlorophenyl)-ethane (DDT) and its main metabolite 1,1-Dichloro-2,2-bis (p, p'-chlorophenyl) ethylene (DDE) act as endocrine disruptors in humans and wildlife. Immunomodulatory functions have also been attributed to both xenobiotics. DDT was banned in the 1970s due to its toxicity, but it is still produced and used for indoor residual spraying with disease vector control purposes. Due to their persistence and lipophilic properties, DDT and DDE can bioaccumulate through the food chain, being stored in organisms' adipose depots. Their endocrine disruptor function is mediated by agonist or antagonist interaction with nuclear receptors. Present review aimed to provide an overview of how DDT and DDE exposure impacts reproductive and immune systems with estrogen-disrupting action in humans and wildlife. Studies showing DDT and DDE impact on mitochondrial function and apoptosis pathway will also be reviewed, suggesting the hypothesis of direct action on mitochondrial steroid receptors.


Assuntos
DDT/toxicidade , Diclorodifenil Dicloroetileno/toxicidade , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Inseticidas/toxicidade , Mitocôndrias/efeitos dos fármacos , Animais , Animais Selvagens , Humanos , Mitocôndrias/metabolismo , Receptores de Esteroides/metabolismo
14.
Toxics ; 9(11)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34822661

RESUMO

Dichlorodiphenyldichloroethylene (DDE), the primary persistent metabolite of dichlorodiphenyltrichloroethane (DDT), has toxic effects on cells, but its dose-dependent impact on mitochondrial proteins involved in mitochondrial fusion and fission processes associated with cell viability impairment has not yet been analysed. Mitochondrial fusion and fission processes are critical to maintaining the mitochondrial network and allowing the cell to respond to external stressors such as environmental pollutants. Fusion processes are associated with optimizing mitochondrial function, whereas fission processes are associated with removing damaged mitochondria. We assessed the effects of different DDE doses, ranging between 0.5 and 100 µM, on cell viability and mitochondrial fusion/fission proteins in an in vitro hepatic cell model (human hepatocarcinomatous cells, HepG2); the DDE induced a decrease in cell viability in a dose-dependent manner, and its effect was enhanced in conditions of coincubation with dietary fatty acids. Fusion protein markers exhibited an inverted U-shape dose-response curve, showing the highest content in the 2.5-25 µM DDE dose range. The fission protein marker was found to increase significantly, leading to an increased fission/fusion ratio with high DDE doses. The low DDE doses elicited cell adaption by stimulating mitochondrial dynamics machinery, whereas high DDE doses induced cell viability loss associated with mitochondrial dynamics to shift toward fission. Present results are helpful to clarify the mechanisms underlying the cell fate towards survival or death in response to increasing doses of environmental pollutants.

15.
Nutrients ; 12(2)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31973152

RESUMO

BACKGROUND AND AIM: Excess sodium intake is a recognised causal factor of hypertension and its cardiovascular complications; there is however a lack of practical instruments to assess and monitor the level of knowledge and behaviour about dietary salt intake and to relate these factors to the population general dietary habits. METHODS AND RESULTS: A self-administered questionnaire was developed to assess the salt and health related knowledge and behaviour of the Italian population through an online survey. A sample of 11,618 Italian participants completed the questionnaire. The degree of knowledge and the reported behaviour about salt intake were both found to be related to age, gender, home region, level of education and occupation. There was a significant interrelation between salt knowledge and behaviour and both were significantly and directly related to the degree of adherence to a Mediterranean-like dietary pattern. A hierarchical evaluation was also made of the relevance of any single question to the overall assessment of knowledge and behaviour about salt intake. CONCLUSIONS: The study population overall appeared to have a decent level of knowledge about salt, but a less satisfactory behaviour. Our findings point to social inequalities and young age as the main factors having a negative impact on knowledge and behaviour about salt intake as part of generally inadequate dietary habits. The degrees of knowledge and behaviour were significantly and directly interrelated, confirming that improving knowledge is a key step for behavioural changes, and suggesting that educational campaigns are crucial for the implementation of good practices in nutrition.


Assuntos
Dieta Saudável/psicologia , Comportamento Alimentar/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Cloreto de Sódio na Dieta/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
16.
J Nutr Biochem ; 78: 108342, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32004927

RESUMO

The activation of endoplasmic reticulum (ER) stress and a reduction of AMP-dependent protein kinase (AMPK) phosphorylation have been described in obesity. We hypothesize that a moderate caloric restriction (CR) might contribute to reducing ER stress and increasing AMPK phosphorylation in peripheral tissues from genetically obese Zucker fa/fa rats and in peripheral blood mononuclear cells (PBMCs). Zucker Lean and Zucker fa/fa rats were fed with chow diet either ad libitum (AL) (C, as controls) or 80% of AL (CR) for 2 weeks, giving rise to four experimental groups: Lean C, Lean CR, fa/fa C and fa/fa CR. CR significantly increased AMPK phosphorylation in the liver, perirenal adipose tissue (PRAT) and PBMCs from fa/fa rats but not in the subcutaneous AT (SCAT), suggesting a reduced response of SCAT to CR. Liver samples of fa/fa rats exhibited an increased mRNA expression of PERK, EIF-2α, XBP-1(s), Chop and caspase 3, which was significantly reduced by CR. PRAT exhibited an overexpression of Edem and PDIA-4 in fa/fa rats, but only PDIA-4 expression was reduced by CR. eIF-2α phosphorylation was significantly increased in all studied tissues from fa/fa rats and reduced by CR. A negative correlation was detected between p-AMPK and p-eIF-2α in the liver, PRAT and PBMCs from fa/fa rats but not in SCAT. This study shows that a moderate CR reduces ER stress and improves AMPK phosphorylation in several peripheral tissues and in circulating PBMCs, suggesting that alterations observed in PBMCs could reflect metabolic alterations associated with obesity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Restrição Calórica , Estresse do Retículo Endoplasmático , Leucócitos Mononucleares/metabolismo , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Animais , Peso Corporal , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Obesidade/metabolismo , Fosforilação , Ratos , Ratos Zucker
17.
J Hepatol ; 51(2): 363-70, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19464748

RESUMO

BACKGROUND/AIMS: Mitochondrial dysfunction is central to the physiopathology of steatosis and/or non-alcoholic fatty liver disease. In this study on rats we investigated whether 3,5-diiodo-l-thyronine (T2), a biologically active iodothyronine, acting at mitochondrial level is able to reverse hepatic steatosis after its induction through a high-fat diet. METHODS: Hepatic steatosis was induced by long-term high-fat feeding of rats for six weeks which were then fed the same high-fat diet for the next 4 weeks and were simultaneously treated or not treated with T2. Histological analyses were performed on liver sections (by staining with Sudan black B). In liver mitochondria fatty acid oxidation rate, mitochondrial efficiency (by measuring proton conductance) and mitochondrial oxidative stress (by measuring H(2)O(2) release, aconitase and SOD activity) were detected. RESULTS: Stained sections showed that T2 treatment reduced hepatic fatty accumulation induced by a high-fat diet. At the mitochondrial level, the fatty acid oxidation rate and carnitine palmitoyl transferase activity were enhanced by T2 treatment. Moreover, by stimulating mitochondrial uncoupling, T2 caused less efficient utilization of fatty acid substrates and ameliorated mitochondrial oxidative stress. CONCLUSION: These data demonstrate that T2, by activating mitochondrial processes, markedly reverses hepatic steatosis in vivo.


Assuntos
Di-Iodotironinas/uso terapêutico , Fígado Gorduroso/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Gorduras na Dieta/administração & dosagem , Di-Iodotironinas/administração & dosagem , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Lipídeos/sangue , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Wistar , Tireotropina/sangue , Aumento de Peso/efeitos dos fármacos
18.
PLoS One ; 14(4): e0215955, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31022254

RESUMO

Oxidative stress plays a key role in steatohepatitis induced by both xenobiotic agents and high fat diet (HFD). The present study aimed to evaluate hepatic oxidative stress and anti-oxidant systems response in rats exposed to HFD and/or non-toxic dose of dichlorodiphenyldichloroethylene (DDE), the first metabolite of dichlorodiphenyltrichloroethane. Groups of 8 rats were so treated for 4 weeks: 1- standard diet (N group); 2- standard diet plus DDE (10 mg/kg b.w.) (N+DDE group); 3- HFD (D group); 4- HFD plus DDE (D+DDE group). Oxidative stress was analyzed by determining malondialdehyde as lipid peroxidation product, while the anti-oxidant systems were evaluating by measuring the levels of the principal cytosolic and mitochondrial antioxidant proteins and enzymes, namely superoxide dismutase 1 and 2 (SOD1, SOD2), glutathione peroxidase 1 (GPx1) and uncoupling protein 2 (UCP2) involved in the control of hepatic reactive oxygens species (ROS) accumulation. The results showed malondialdehyde accumulation in livers of all groups, confirming the pro-oxidant effects of both HFD and DDE, but with a greater effect of DDE in absence of HFD. In addition, we found different levels of the analyzed anti-oxidant systems in the different groups. DDE mainly induced UCP2 and SOD2, while HFD mainly induced GPx1. Noteworthy, in the condition of simultaneous exposure to DDE and HFD, the anti-oxidant response was more similar to the one induced by HFD than to the response induced by DDE. Present findings confirmed that both HFD and xenobiotic exposure induced hepatic oxidative stress and showed that the anti-oxidant defense response was not the same in the diverse groups, suggesting that UCP2 induction could be an adaptive response to limit excessive ROS damage, mainly in condition of xenobiotic exposure.


Assuntos
Diclorodifenil Dicloroetileno/toxicidade , Dieta Hiperlipídica , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Estresse Oxidativo/efeitos dos fármacos , Proteína Desacopladora 2/metabolismo , Xenobióticos/toxicidade , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antioxidantes/metabolismo , Citocromo P-450 CYP2B1/metabolismo , Fígado Gorduroso/sangue , Regulação da Expressão Gênica/efeitos dos fármacos , Dissulfeto de Glutationa/metabolismo , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/análise , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Metaboloma/efeitos dos fármacos , Oxirredução , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Proteína Desacopladora 2/genética , Aumento de Peso/efeitos dos fármacos
19.
Sci Total Environ ; 670: 1170-1183, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31018433

RESUMO

The variations of haematological parameters hematocrit, hemoglobin concentration, leukocyte and erythrocyte count have been used as pollution and physiological indicators of organic dysfunction in both environmental and aquaculture studies. These parameters are commonly applied as prognostic and diagnostic tools in fish health status. However, there are both extrinsic and intrinsic factors to consider when performing a blood test, because a major limitation for field researchers is that the "rules" for animal or human haematology do not always apply to wildlife. The main objective of this review is to show how some environmental and xenobiotic factors are capable to modulating the haematic cells. Visualizing the strengths and limitations of a haematological analysis in the health assessment of wild and culture fish. Finally, we point out the importance of the use of mitochondrial activities as part of haematological evaluations associated to environment or aquaculture stress.


Assuntos
Meio Ambiente , Doenças dos Peixes/diagnóstico , Peixes , Testes Hematológicos/veterinária , Poluentes Químicos da Água/efeitos adversos , Xenobióticos/efeitos adversos , Animais , Doenças dos Peixes/induzido quimicamente , Doenças dos Peixes/etiologia , Doenças dos Peixes/fisiopatologia , Hematologia/métodos , Prognóstico , Estresse Fisiológico/efeitos dos fármacos
20.
Cells ; 8(8)2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387296

RESUMO

In our modern society, exposure to stressful environmental stimuli, such as pollutants and/or chronic high-fat feeding, continuously induce tissular/organ metabolic adaptation to promote cellular survival. In extreme conditions, cellular death and tissular/organ damage occur. Mitochondria, as a cellular energy source, seem to play an important role in facing cellular stress induced by these environmental stimuli. On the other hand, mitochondrial dysfunction and oxidative stress play a key role in environmental stress-induced metabolic diseases. However, little is known about the combined effect of simultaneous exposure to chronic high-fat feeding and environmental pollutants on metabolic alterations at a tissular and cellular level, including mitochondrial dysfunction and oxidative stress induction. Our research group recently addressed this topic by analysing the effect of chronic exposure to a non-toxic dose of the environmental pollutant dichlorodiphenyldichloroethylene (DDE) associated with high-fat feeding in male Wistar rats. In this review, we mainly summarize our recent findings on mitochondrial adaptive response and oxidative stress induction in the liver, the main tissue involved in fat metabolism and pollutant detoxification, and in male gonads, the main targets of endocrine disruption induced by both high-fat feeding and environmental pollutants.


Assuntos
Adaptação Fisiológica , Dieta Hiperlipídica/efeitos adversos , Inseticidas/toxicidade , Fígado/metabolismo , Mitocôndrias/metabolismo , Testículo/metabolismo , Animais , Fígado/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo , Ratos , Testículo/efeitos dos fármacos
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