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To evaluate the effects of melatonin (MEL) on the expression of toll-like receptor-4 (TLR4); myeloid differentiation primary response protein-88 (MyD88); TIR-domain-containing adapter-inducing interferon-ß (TRIF); IFN regulatory-factor-3 (IRF-3); nuclear factor kappa-B (NF-κB); plasma concentrations of interleukin-1ß (IL-1ß) and lipopolysaccharide (LPS); and lipid profile of rats with apical periodontitis (AP) fed on a high-fat diet (HFD). Eighty 60-day-old rats were divided into eight groups: control, AP, HFD, HFDAP, CNMEL, APMEL, HFDMEL and HFDAPMEL. HFD groups were fed on a HFD for 107 days. On day 7, experimental AP was induced in the AP groups, and after 70 days, MEL (5 mg/kg) was administered to the MEL groups for 30 days. Plasma concentrations of LPS and IL-1ß were analyzed using enzyme-linked immunosorbent assay, and the lipid profile was analyzed using biochemical tests. The expression of proteins involved in the TLR4 pathway (TLR4, MyD88, TRIF, IRF-3 and NF-κB) in the gastrocnemius muscle (GM) was evaluated using western blotting and qRT-PCR. Treatment with MEL decreased IRF-3 protein expression in GM and IL-1ß plasma concentration in the APMEL and HFDMEL groups. Reduction in LPS plasma concentration was reported only in the HFDMEL group. Additionally, a decrease in LDL and an increase in HDL were observed in the HFDMEL and HFDAPMEL groups. Treatment with MEL exhibited anti-inflammatory and anti-hyperlipidemic effects attributed to HFD and AP by reducing the plasma concentrations of IL-1ß and LPS in addition to reducing IRF-3 protein expression in the GM, which is associated with the production of inflammatory cytokines.

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AIM: To analyse the effects of melatonin (ME) treatment on oxidative stress and insulin resistance (IR) in rats with apical periodontitis (AP) fed a high-fat diet (HFD). METHODOLOGY: Eighty 60-day-old rats were divided into eight groups: control (CN), AP, HFD with AP (HFDAP), control with ME (CNME), AP with ME (APME), HFD with ME (HFDME) and HFD with AP+ME (HFDAPME). The animals from the HFD groups were fed a HFD throughout the experimental period. On day 7, the animals from the AP groups were subjected to experimental AP, and after 70 days, the ME groups were treated for 30 days. Glycaemia, insulinaemia, homeostatic model assessment for IR index, tumour necrosis factor-α (TNF-α), and interleukin-6 were analysed in plasma using biochemical tests and enzyme-linked immunosorbent assay. Thiobarbituric acid-reactive substances (TBARS), carbonyl protein (CP), superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione (GSH) and total antioxidant capacity (ferric reducing antioxidant power [FRAP]) were analysed in the gastrocnemius muscle. RESULTS: (1) Association of AP and HDF exacerbated IR, and ME treatment improved this alteration; (2) AP and HFD and their association showed increased TNF-α, and ME reversed it; (3) TBARS increased in the AP and HFDAP groups, and ME reversed only in the group with the association of disease and diet; (4) CP increased in all HFD groups and improved in the ME groups; (5) GSH activity decreased in all experimental groups, and ME increased this parameter only in the CN and AP groups; (6) FRAP did not change between the groups, but ME treatment increased its activity in the AP and HFD groups; (7) ME increased SOD in the CN and AP groups. CONCLUSION: Apical periodontitis and HFD promoted IR, and the association of AP with diet promoted IR exacerbation; this resistance might have been caused by an increase in TNF-α. AP promoted more intense changes in lipid oxidative damage than in protein oxidative damage. In non-enzymatic antioxidant defence, it was observed that both AP and HFD and their association promoted a decrease in GSH levels. Overall, ME treatment reversed changes such as oxidative stress and IR.

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BACKGROUND: Maternal periodontal disease (PED) and apical periodontitis (AP) are associated insulin resistance (IR), increased tumor necrosis factor-α (TNF-α) levels, and alterations in insulin signaling (IS) in the gastrocnemius muscle (GM) of adult offspring. TNF-α stimulates I kappa B kinase (IKK) and c-Jun N-terminal protein kinase (JNK), resulting in IS attenuation. However, studies that investigated the maternal true endodontic-periodontal lesion (EPL) in offspring are scarce, and in this case, the impact could be even higher. This study aimed to evaluate the effects of EPL on the IR, IS, and inflammatory pathways on the offspring GM. METHODS: Female Wistar rats were distributed into control, AP, PED, and EPL groups. After 30 days of oral inflammation induction, rats from all groups were allowed to mate with healthy rats. The body weight of the offspring was assessed from birth to 75 days of age. After 75 days, the following measurements were performed: glycemia, insulinemia, IR, TNF-α content, and IKKα/ß, JNK, pp185 (Tyr), and IRS-1 (Ser) phosphorylation status in the GM. RESULTS: Maternal PED and EPL were associated with low birth weights. All maternal oral inflammations promoted IR and IS impairment in the GM and only maternal PED and EPL caused an increase in TNF-α content and IKKα/ß phosphorylation status in the GM of offspring. The offspring of the rats with EPL group showed worsening of metabolic changes when compared with offspring of rats with AP or PED. CONCLUSION: Association of maternal AP and PED promoted a more pronounced worsening in the health of the adult offspring.

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OBJECTIVE: The study aimed to assess the effects of mate tea [Ilex paraguariensis] on the redox state and biochemical parameters of salivary glands in diabetic male rats. DESIGN: Twenty-four male Wistar rats (3 months old) were randomly divided into groups (n = 8 per group): control rats that received water (C); diabetic rats that received water (D); diabetic rats treated with mate tea (DMT). The treated streptozotocin-induced diabetic rats were given mate tea powder by intragastric gavage at a dose of 20 mg/kg daily for 28 days. Content of total protein, amylase, oxidative lipid damage, measured as thiobarbituric acid reactive substances (TBARs), oxidative protein damage, measured as protein carbonyl, total antioxidant capacity, uric acid, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were examined by the spectrophotometric method in the parotid and submandibular glands. RESULTS: The D group showed lower total protein, amylase, TBARs, protein carbonyl, total antioxidant capacity, GSH, uric acid, and GPx than the C group in both salivary glands, as well as higher SOD and CAT activities. The DMT group showed higher total protein, amylase, total antioxidant capacity, GSH, uric acid, and GPx than the D group in both salivary glands. Moreover, mate tea increased SOD in the parotid gland and CAT in the submandibular gland of diabetic rats but did not influence TBARs and protein carbonyl in either salivary gland compared to D group. CONCLUSION: Mate tea increased tissue protein synthesis and improved antioxidant defenses in the salivary glands of streptozotocin-induced diabetic male rats.

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OBJECTIVE: Apical periodontitis (AP) is a chronic or acute inflammatory disease usually developed from endodontic infections, predominantly due to gram-negative anaerobic bacteria invading the dental pulp. This study aimed to evaluate lymphocyte markers to assess the involvement of adaptive immunity in insulin resistance (IR) in a rat model of AP.Design.Forty-five male Wistar albino rats were divided into 3 groups (control, 1AP and 4AP). AP was induced in the upper right first molar (1AP), and in the first and second upper and lower right molars (4AP). The spleen was collected to evaluate the expression of transcription factors involved in lymphocyte polarization, including T-bet (Th1), GATA3 (Th2), and FOXP3 (Treg). Blood samples were assessed for serum cytokine levels transcribed by the respective lymphocyte polarizations, INF-γ (Th1), IL-4 (Th2) and TGF-ß (Treg). In addition, glucose and insulin levels were measured to evaluate IR by the HOMA-IR method. RESULTS: The results showed higher T-bet expression on AP groups, along with lower GATA3 and FOXP3 expression in the 1AP, in addition to increased GATA3 and decreased FOXP3 expression in the 4AP group compared to the CN group. There was no difference in the INF-γ levels, while IL-4 was decreased in the AP groups. Taken together, these results suggest that the adaptive immune system, with a predominance of the Th1 polarization, may be involved in the development of IR in rats with AP. CONCLUSIONS: AP promotes increase in the expression of T-bet (4AP) and decrease of FOXP3 expressions and IL-4 levels (1AP and 4AP). However, depending on the number of lesions (1 or 4 lesions), the expression of GATA3 appears differently. Thus, innate immunity and adaptive immunity may contribute to the IR observed in rats with AP.

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AIM: To evaluate the final step of insulin signalling, inflammatory pathway (related to the inhibition of insulin signalling), peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) protein content and DNA methylation in the Slc2a4 gene promoter region in the skeletal muscle of adult male offspring of rats with apical periodontitis (AP) in a single tooth or in four teeth. METHODOLOGY: Female Wistar rats were distributed into three groups: a control group, a group with one tooth with AP and a group with four teeth with AP. Thirty days after induction of AP, female rats from all groups were mated with healthy male rats. When male offspring reached 75 days of age, the following analyses were performed in the gastrocnemius muscle (GM): insulin-stimulated Akt serine and threonine phosphorylation status; NF-κB p50 and p65 subunits phosphorylation status; GLUT4, TNF-α and PGC-1α protein content by Western blotting; GLUT4 and TNF-α gene expression by real-time polymerase chain reaction (PCR); and DNA methylation in the Slc2a4 gene promoter region by restriction digestion and real-time PCR. Analysis of variance was performed, followed by Tukey's post hoc test. p values <.05 were considered to be statistically significant. RESULTS: Maternal AP in four teeth decreased insulin-stimulated Akt serine and threonine phosphorylation status, reduced GLUT4 gene expression and its protein content, and increased NF-κB p50 and p65 subunits phosphorylation status in the GM of adult offspring. There were no alterations in the parameters analysed in the GM of adult offspring of rats with AP in a single tooth. In addition, maternal AP did not affect TNF-α gene expression and its protein content, PGC-1α protein content and DNA methylation in the Slc2a4 gene promoter region in the GM of adult offspring. CONCLUSIONS: Maternal AP in four teeth was associated with impairment in the final step of insulin signalling in the GM of adult male offspring in rats. An increase in NF-κB activity may be involved in this decrease in insulin signalling. This study demonstrates the impact of maternal AP on the health of offspring, demonstrating the importance of maintaining adequate maternal oral health to prevent diseases in adult offspring in rats.

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INTRODUCTION: Maternal apical periodontitis (AP) is associated with insulin resistance (IR) in adult offspring. Oxidative stress has been linked to IR. This study investigated insulin sensitivity (IS) and oxidative stress in the gastrocnemius muscle (GM) of adult offspring of rats with AP. METHODS: Fifteen female Wistar rats were distributed into a control group, a group with 1 tooth with AP, and a group with 4 teeth with AP. Thirty days after AP induction, female rats were mated with healthy male rats. When male offspring reached 75 days of age, glycemia, insulinemia, and IS were determined. In the GM, the oxidative damage products (thiobarbituric acid reactive substances and carbonyl protein) and activities of enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) and nonenzymatic (glutathione and total antioxidant capacity) antioxidants were quantified. Analysis of variance was performed followed by the Tukey post hoc test (P < .05). RESULTS: Maternal AP was associated with decreased IS and changes in antioxidant activities (reduced superoxide dismutase and increased catalase, glutathione peroxidase, and glutathione) and decreased thiobarbituric acid reactive substance concentration in the GM of their adult offspring. However, maternal AP does not appear to affect glycemia, carbonyl protein concentration, and the nonenzymatic total antioxidant capacity in the GM of this offspring. CONCLUSIONS: Maternal AP modulates the antioxidant defense system in the GM of their adult offspring, attenuating lipid peroxidation in this tissue. This reflects part of an adaptive response of the offspring to the stimulation of the maternal chronic oral inflammatory process in which the organism acts by decreasing oxidative tissue damage in the postnatal stage. The present study improves knowledge about the impact of maternal oral inflammation on healthy offspring.

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Resumen Las floraciones de algas nocivas son un problema cada vez más frecuente a nivel mundial que ocasiona severos daños sobre la salud pública, pérdidas económicas en acuicultura, perjuicios al turismo y episodios de mortalidad de poblaciones naturales de peces, aves y mamíferos marinos. Las toxinas son producidas por el fitoplancton y se acumulan en moluscos bivalvos que se alimentan por filtración del agua siendo estos los principales vectores de intoxicación humana. En el Mar Argentino, se han reportado toxinas marinas de origen microalgal asociadas con cuatro síndromes de intoxicación por moluscos. Los síndromes más graves por su extensión, frecuencia, toxicidad y organismos afectados, son los originados por el dinoflagelado Alexandrium cate-nella responsable de la Intoxicación Paralizante por Moluscos la cual ha ocasionado numerosas muertes humanas. Seguidamente, la más leve, en cuanto a gravedad y frecuencia, ha sido la Intoxicación Diarreica por Moluscos. En contraste, el ácido domoico, conocido como toxina amnésica de moluscos, no ha producido hasta ahora intoxicaciones humanas. Recientemente, se amplió el rango de toxinas para la región al registrarse las toxinas y los dinoflagelados productores de la Intoxicación Azaspirácidos por Moluscos. Además, se han detectado las potencialmente tóxicas Yessotoxinas y Espirolidos, cuyos mecanismos de acción y toxicidad están siendo aún evaluados a nivel mundial. Estas toxinas emergentes para la región, representan un riesgo potencial para la salud e inconvenientes socioeconómicos por el cierre de los sitios de explotación de moluscos. Ciertamente presentan un nuevo desafío, pues la detección y cuantificación sólo puede realizarse por medio de métodos basados en HPLC - espectrometría de masas, lo cual dificulta el monitoreo en laboratorios regionales en el país. La herramienta clave de manejo es la prevención, a través de políticas, regulaciones y sistemas de monitoreo y control de cada grupo de toxinas. A través de estas mejoras, se anticipa que no sólo disminuirá el número de afectados por estas intoxicaciones, si no que se podrán realizar vedas más eficientes, asegurando un equilibrio que proteja tanto la salud pública como el desarrollo de la industria pesquera.

Abstract Harmful algal blooms are an increasingly common problem worldwide, causing severe damage to public health, economic losses in aquaculture, damage to tourism and mortality events of natural populations of fish, birds and marine mammals. The toxins are produced by phytoplankton and accumulated in bivalve molluscs that feed on water filtration, being these main vectors of human intoxication. In the Argentine Sea marine toxins of microalgal origin have been reported associated with four shellfish poisoning syn-dromes. The most serious due to their extension, frequency, toxicity and affected organisms are those caused by the dinoflagellate Alexandrium catenella responsible for the Paralytic shellfish poisoning that has caused numerous human deaths. Then, the mildest, in severity and frequency, is the Diarrhetic shellfish poisoning. In contrast, domoic acid, known as Amnesic shellfish toxin, has not produced human intoxications yet. Recently, toxins and dinoflagellate species causing Azaspiracid shellfish poisoning have been re-corded, expanding the range of toxins for the region. In addition, the potentially toxic Yessotoxins and Spirolides have been detected, whose mechanism of action and toxicity is still being evaluated worldwide. These emerging toxins represent a potential risk to public health and socioeconomic activities due to the eventual closure of mollusc exploitation sites. They certainly present a new challenge, since detection and quantification can only be carried out using methods based on HPLC - mass spectrometry, which makes monitor-ing in regional laboratories difficult. Prevention through policies, regulations, and monitoring and control systems of each toxin group is the key management tool. These preventive measures are expected to contribute to reducing the number of poisonings and to ap-plying more efficient fisheries closures, ensuring a balance that protects both public health and the development of the fishing industry.

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Trees are constantly exposed to climate fluctuations, which vary with both time and geographic location. Environmental changes that are outside of the physiological favorable range usually negatively affect plant performance and trigger responses to abiotic stress. Long-living trees in particular have evolved a wide spectrum of molecular mechanisms to coordinate growth and development under stressful conditions, thus minimizing fitness costs. The ongoing development of techniques directed at quantifying abiotic stress has significantly increased our knowledge of physiological responses in woody plants. However, it is only within recent years that advances in next-generation sequencing and biochemical approaches have enabled us to begin to understand the complexity of the molecular systems that underlie these responses. Here, we review recent progress in our understanding of the molecular bases of drought and temperature stresses in trees, with a focus on functional, transcriptomic, epigenetic, and population genomic studies. In addition, we highlight topics that will contribute to progress in our understanding of the plastic and adaptive responses of woody plants to drought and temperature in a context of global climate change.

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BACKGROUND: Maternal periodontal disease leads to low birth weight (LBW), insulin resistance (IR), increased TNF-α levels, and alterations in insulin signaling in adult offspring. TNF-α has been associated with the stimulation of IKKß/NF-κB, resulting in the decreased expression of GLUT4. Another mechanism that may be involved in decreasing GLUT4 expression is DNA methylation. This study aimed to evaluate in the adult offspring of rats with periodontal disease: IR, inflammatory pathways, DNA methylation, and expression of GLUT4. METHODS: Female Wistar rats were distributed into control and experimental periodontal disease groups. Seven days after induction of periodontal disease, both groups were mated with healthy male rats. After weaning, male offspring were distributed into control offspring (CN-o) and periodontal disease offspring (PED-o) groups. Body weights were measured from 0-75 days of age. At day 75, the following were measured in the offspring: IR (HOMA-IR index); TNF-α and NF-κBp65 content in the gastrocnemius muscle (GM) by western blotting; IKKα/ß, JNK, ERK 1/2, NF-κBp65, and NF-κBp50 phosphorylation status in the GM by western blotting; DNA methylation by restriction digest and real-time PCR(qAMP); and expression of GLUT4 mRNA in the GM by real-time PCR. RESULTS: LBW, IR, increases in TNF-α, IKKα/ß, ERK 1/2, NF-κBp65, and NF-κBp50 decreased expression of GLUT4 mRNA were observed in the PED-o rats. No differences were identified in JNK phosphorylation status and DNA methylation in the evaluated regions of the GLUT4-encoding gene Slc2a4. CONCLUSION: Maternal periodontal disease causes LBW, IR, activation of inflammatory pathways, and decreased GLUT4 expression in the GM of adult offspring.

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Atualmente, está bem estabelecido que o ambiente fetal está ligado à saúde materna, e estímulos ou agressões anormais durante a vida intra-uterina podem resultar em mudanças na fisiologia e metabolismo da prole, aumentando o risco de doenças na vida adulta. Tal fenômeno é conhecido como programação fetal. Alterações na metilação do DNA e expressão gênica são consideradas mecanismos moleculares responsáveis por esta programação. Estudos anteriores demonstraram que a doença periodontal (DP) materna promove resistência insulínica, aumento nas concentrações plasmáticas de citocinas, redução do conteúdo de GLUT4 e do seu índice de translocação para membrana plasmática em sua prole adulta. E citocinas, como por exemplo, o TNF-α, têm sido relacionadas com a redução da expressão de GLUT4 por meio da ativação do fator de transcrição nuclear κappa B (NF-κB). Além disso, esta citocina pode estimular algumas serinas quinases, incluindo IκB quinase (IKK), c-Jun amino-terminal kinase (JNK) e quinases reguladas por sinais extracelulares (ERKs) que estão envolvidas na resistência insulínica. Tais achados evidenciam a necessidade de realizar mais estudos para verificar os mecanismos envolvidos nestas alterações. Portanto, os objetivos do presente estudo foram avaliar em ratos adultos, proles de ratas com DP: 1) massa corpórea ao longo de 75 dias de idade; 2) glicemia e insulinemia; 3) expressão do RNAm da proteína transportadora de glicose GLUT4 e do IRS1 em muscular esquelético gastrocnêmio (MG); 4) o grau de metilação do DNA na região promotora do gene do GLUT4 em MG; 5) fosforilação das proteínas JNK, IKKα/ß, ERK 1/2, NF-κBp65 e NF-κBp50 e seus conteúdos totais em MG; 6) conteúdo total de TNF-α em MG. As ratas foram divididas em dois grupos: 1) com doença periodontal (DP), no qual esta doença foi induzida por meio de ligadura com fio de seda ao redor do 1º molar inferior; 2) ratas controle (CN). Após 7 dias da colocação da ligadura, as ratas de ambos os grupos foram colocadas para acasalamento, verificou-se diariamente, por esfregaço vaginal, o dia da copulação. As ratas prenhas foram separadas em caixas individuais. Quando os filhotes machos destas ratas completaram 75 dias, realizaram-se os experimentos: 1) glicemia e insulinemia; 2) expressão do RNAm do GLUT4 e do IRS1 em MG; 3) o grau de metilação do DNA na região promotora do gene do GLUT4 em MG; 4) fosforilação das proteínas JNK, IKKα/ß, ERK 1/2, NF-κBp65 e NF-κBp50 e seus conteúdos totais em MG; 5) conteúdo total de TNF-α em MG. Os resultados demonstraram que a doença periodontal materna promove na sua prole adulta baixo peso ao nascimento (BPN), resistência insulínica, aumento do conteúdo total de TNF-α em MG, aumento do grau de fosforilação de IKKα/ß, ERK 1/2, NF-κBp65 (grau de fosforilação e conteúdo) e NF-κBp50 em MG, diminuição na expressão gênica da proteína transportadora de glicose GLUT4 e aumento na expressão gênica do IRS1; porém não promove nessa prole alteração no grau de metilação do DNA na região promotora do gene do GLUT4, e no grau de fosforilação da proteína JNK em MG. Portanto, este estudo é de fundamental importância para o entendimento de alguns dos mecanismos envolvidos na relação entre a doença periodontal materna e resistência à insulina na prole adulta. Além disso, mostra que a saúde bucal materna ideal pode ajudar a prevenir doenças futuras na prole adulta(AU)

It is well established that the fetal environment is linked to maternal health, and abnormal stimuli or aggressions during intrauterine life can result in changes in the physiology and metabolism of offspring, increasing the risk of disease in adult life, this phenomenon is known as fetal programming. Changes in DNA methylation and gene expression are considered molecular mechanisms responsible for this programming. Previous studies have demonstrated that maternal periodontal disease (PD) promotes insulin resistance, increased plasma concentrations of cytokines, reduced GLUT4 content and its plasma membrane translocation index in its adult offspring. And cytokines, such as TNF-α, have been linked to reduced GLUT4 expression through the activation of nuclear transcription factor kappa B (NF-κB). In addition, this cytokine can stimulate some serine kinases including IκB kinase (IKK), c-Jun amino-terminal kinase (JNK) and extracellular signal­regulated kinases (ERKs) that are involved in insulin resistance. These findings evidenced the need for further studies to verify the mechanisms involved in these changes. Therefore, the objectives of the present study were to evaluate in adult rats, offspring of rats with PD: 1) birth weight and during the 75 days of age; 2) glycemia and insulinemia; 3) GLUT4 and IRS1 mRNA expression in skeletal muscle gastrocnemius (MG); 4) the degree of DNA methylation in the promoter region of the GLUT4 gene in MG; 5) phosphorylation of JNK, IKKα/ß, ERK 1/2, NF-κBp65 and NF-κBp50 proteins and their total contents in MG; 6) TNF-α content in MG. Female Wistar rats were distributed into a control group and an experimental periodontal disease group, in which the disease is induced by ligation with silk thread around the 1st molar. Seven days after ligature placement, animals from both groups mated and daily vaginal smears were taken to verify the presence of sperm. Pregnant rats were kept in individual cages. The body weights of the offspring were measured once weekly from birth until 75 days of age. When male offspring of these rats completed 75 days, the experiments were performed: 1) glycemia and insulinemia; 2) GLUT4 and IRS1 mRNA expression in skeletal muscle gastrocnemius (MG); 3) the degree of DNA methylation in the promoter region of the GLUT4 gene in MG; 4) phosphorylation of JNK, IKKα/ß, ERK 1/2, NF-κBp65 and NF-κBp50 proteins and their total contents in MG; 5) TNF-α content in MG. The results demonstrated that maternal periodontal disease promotes in its adult offspring low birth weight (LBW), insulin resistance, increased TNF-α content in MG, increased IKKα/ß, ERK 1/2, NF-κBp65 (phosphorylation status and content) and NF-κBp50 phosphorylation status in the MG, decrease in gene expression of GLUT4 and increase in IRS1 gene expression; but does not promote in this progeny change in the degree of DNA methylation in the promoter region of the GLUT4 gene, and JNK phosphorylation status in MG. Therefore, this study is of fundamental importance for the understanding of some of the mechanisms involved in the relationship between maternal periodontal disease and insulin resistance in adult offspring. In addition, it shows that ideal maternal oral health can help prevent future illnesses in adult offspring(AU)

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AIM: This study aimed to investigate the effects of melatonin (ME) on insulin resistance (IR) and signaling (IS), proinflammatory cytokine levels, and lipid profiles in pinealectomyzed (PNX) rats with periodontal disease (PD). MAIN METHODS: One hundred and forty-four rats (age = 40 days) were distributed into 8 groups: 1) control (CN); 2) PD only; 3) PNX only; 4) PNX and PD (PNXPD); 5) CN treated with ME (CNM); 6) PD treated with ME (PDM); 7) PNX treated with ME(PNXM); 8) PNX and PD treated with ME(PNXPDM). The PNX groups were subjected to pinealectomy at 40 and at 60 days of age. The animals were then subjected to PD induction in the mandibular first molars. After PD induction, the ME replacement therapy (MERT-5 mg/kg body weight) was performed using water for 28 days. After this period, the plasma concentration of glucose, insulin, TNF, IL-6, triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, and VLDL-cholesterol and the HOMA-IR index were determined. Akt serine phosphorylation status in the white adipose tissue, gastrocnemius muscle, and rat liver were also evaluated. KEY FINDINGS: PD, PNX, and PNXPD groups showed an increase in IR with elevated plasma levels of insulin and TNF compared to CN group. PNX and PNXPD groups presented alteration in lipid profile compared to CN group. MERT improved all of the analyzed parameters. No difference was observed in the IS among different groups. SIGNIFICANCE: The results suggest that MERT efficiently prevents IR, improves lipid profile, and increases plasma levels of insulin and TNF in PD and PNX rats.

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INTRODUCTION: Our previous studies have shown that periapical lesions (PLs) in rats cause systemic disorders such as increased tumor necrosis factor-α plasma levels, insulin resistance, and impairment in insulin signal transduction in muscle tissue. However, the mechanisms involved in these alterations are not fully understood. Under chronic inflammatory conditions such as obesity, it has been shown that the skeletal muscle is affected by inflammation, and the number of resident macrophages that are associated with impairments of insulin action and sensitivity is increased. This study aimed to investigate the presence of macrophages, activation of inflammatory pathways in muscle tissue, glycemia, and insulinemia of rats with PLs. METHODS: Sixty Wistar rats were distributed into a control group; a group with 1 PL (1PL), which was induced in the right maxillary first molar; and a group with 4 PLs (4PL), which were induced in the right upper and lower first and second molars. We quantified macrophage content by immunohistochemistry for the F4/80 protein. We evaluated Jun N-terminal kinase and IKKα/ß phosphorylation status in the muscle tissue by Western blotting. Serum levels of lipopolysaccharide (LPS) and HSP70 and plasma levels of glucose and insulin were assessed by using commercial kits. RESULTS: The 1PL and 4PL groups showed increase in macrophage content, IKKα/ß, and Jun N-terminal kinase phosphorylation status, serum LPS and HSP70 levels, and insulin resistance and no changes in glycemia and insulinemia compared with the control group. There was no difference in these parameters between the 1PL and 4PL groups. CONCLUSIONS: PLs promoted an increase in macrophage infiltration, activation of inflammatory pathways in muscle tissue, and serum concentrations of HSP70 and LPS in rats. The present study improves the knowledge on the impact of oral inflammations on the development of systemic alteration, which can induce insulin resistance.

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Fluoride is an essential trace element for the maintenance of bone health owing to its capacity to stimulate proliferation and osteoblastic activity that can lead to increased bone formation. However, excessive sodium fluoride (NaF) intake can impair carbohydrate metabolism thereby promoting hyperglycemia, insulin resistance, and changes in insulin signaling. Thus, this study aimed to evaluate the effect of chronic treatment with NaF in bone metabolism, insulin signaling, and plasma concentrations of glucose, insulin, tumor necrosis factor-α (TNF-α), osteocalcin (OCN), and fluoride in ovariectomized rats. Thirty-two ovariectomized Wistar rats were randomly distributed into two groups: Control (OVX-C) and those undergoing treatment with NaF (50mg F/L) in drinking water for 42days (OVX-F). Glucose and insulin levels were assessed, followed by homeostasis model assessment of insulin resistance (HOMA-IR). Akt serine phosphorylation was evaluated by western blotting. Plasma concentrations of TNF-α and OCN were evaluated by ELISA. The left and right tibia was collected for immunohistochemical and histomorphometric analysis, respectively. Chronic treatment with NaF promoted insulin resistance, decreased insulin signal, increased plasma concentration of insulin, fluoride, OCN and TNF-α, decreased trabecular bone area of the tibia, and caused changes in bone metabolism markers in ovariectomized rats. These results suggest the need for caution in the use of NaF for the treatment of osteoporosis, especially in postmenopausal woman.

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Pregnancy is a period involving important metabolic changes that enable the maintenance of the mother's health and development of the fetus. This study aimed to assess the relationship among periodontal disease, insulin resistance, salivary cortisol concentration and level of perceived stress in pregnant women. This was a cross-sectional study. The sample comprised 96 pregnant women between the fifth and seventh month of pregnancy registered at the Basic Health Units of the Unified Health System (SUS). The periodontal condition was assessed after obtainment free and informed consent from the participants. Participants were divided into three groups: control subjects with a healthy periodontal condition (CN; n=46), patients with gingivitis (GI; n=26), and patients with periodontitis (PI; n=24). Saliva and blood samples were collected for evaluation of salivary cortisol concentration, glycemia, insulinemia and Homeostasis Model Assessment-Insulin Resistance index. A validated survey for the assessment of perceived stress levels was also performed. PI group showed significantly higher (p<0.05) blood glucose levels (CN: 4.43±0.05; GI: 4.46±0.04; PI: 4.68±0.08), insulinemia (CN: 6.93±0.45; GI: 8.87±0.79; PI: 12.77±1.30), insulin resistance (CN: 1.40±0.10; GI: 1.81±0.18; PI: 2.66±0.29) compared with the CN and GI groups. The levels of perceived stress were higher (p<0.05) in PI and GI groups when compared to CN group (CN: 20.5±1.26; GI: 25.8±1.95; PI: 26.6±1.36). There was no significant difference in the concentration of salivary cortisol between the groups (CN: 11.13±0.58; GI: 11.96±0.74; PI: 11.47±0.74). It was concluded that there is a relationship between higher levels of perceived stress, insulin resistance and the occurrence of periodontal disease during pregnancy. This study emphasizes the importance of preventing periodontitis in order to avoid insulin resistance and stress during pregnancy since these can cause systemic complications for the mother and the fetus.

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Abstract Pregnancy is a period involving important metabolic changes that enable the maintenance of the mother's health and development of the fetus. This study aimed to assess the relationship among periodontal disease, insulin resistance, salivary cortisol concentration and level of perceived stress in pregnant women. This was a cross-sectional study. The sample comprised 96 pregnant women between the fifth and seventh month of pregnancy registered at the Basic Health Units of the Unified Health System (SUS). The periodontal condition was assessed after obtainment free and informed consent from the participants. Participants were divided into three groups: control subjects with a healthy periodontal condition (CN; n=46), patients with gingivitis (GI; n=26), and patients with periodontitis (PI; n=24). Saliva and blood samples were collected for evaluation of salivary cortisol concentration, glycemia, insulinemia and Homeostasis Model Assessment-Insulin Resistance index. A validated survey for the assessment of perceived stress levels was also performed. PI group showed significantly higher (p<0.05) blood glucose levels (CN: 4.43±0.05; GI: 4.46±0.04; PI: 4.68±0.08), insulinemy (CN: 6.93±0.45; GI: 8.87±0.79; PI: 12.77±1.30), insulin resistance (CN: 1.40±0.10; GI: 1.81±0.18; PI: 2.66±0.29) compared with the CN and GI groups. The levels of perceived stress were higher (p<0.05) in PI and GI groups when compared to CN group (CN: 20.5±1.26; GI: 25.8±1.95; PI: 26.6±1.36). There was no significant difference in the concentration of salivary cortisol between the groups (CN: 11.13±0.58; GI: 11.96±0.74; PI: 11.47±0.74). It was concluded that there is a relationship between higher levels of perceived stress, insulin resistance and the occurrence of periodontal disease during pregnancy. This study emphasizes the importance of preventing periodontitis in order to avoid insulin resistance and stress during pregnancy since these can cause systemic complications for the mother and the fetus.

Resumo A gravidez é um período que envolve alterações metabólicas importantes que permitem a manutenção da saúde e desenvolvimento fetal e materno. Este estudo teve como objetivo avaliar a relação entre doença periodontal, resistência à insulina, concentração de cortisol salivar e nível de estresse percebido em gestantes. Trata-se de um estudo transversal. A amostra foi composta por 96 gestantes entre o quinto e sétimo mês, registradas em Unidades Básicas de Saúde do Sistema Único de Saúde. A condição periodontal foi avaliada após a obtenção do consentimento livre e esclarecido das participantes. As participantes foram divididas em três grupos: pacientes controle com condição periodontal saudável (CN; n=46), com gengivite (GI; n=26) e com periodontite (PI; n=24). As amostras salivares e sanguíneas foram coletadas para avaliação da concentração salivar de cortisol, glicemia, insulinemia e índice HOMA-IR. Foi aplicado um questionário validado para verificação dos níveis de estresse percebido. Grupo PI apresentou níveis significativamente mais elevados (p<0,05) de glicose no sangue (CN: 4,43±0,05; GI: 4,46±0,04; PI: 4,68±0,08), insulinemia (CN: 6,93±0,45; GI: 8,87±0,79; PI: 12,77±1,30), resistência à insulina (CN: 1,40±0,10; GI: 1,81±0,18; PI: 2,66±0,29) em comparação com os grupos CN e GI. Os níveis de estresse percebido foram maiores (p<0,05) nos grupos PI e GI quando comparados ao grupo CN (CN: 20,5±1,26; GI: 25,8±1,95; PI: 26,6±1,36). Não houve diferença significativa na concentração de cortisol salivar entre os grupos (CN: 11,13±0,58; GI: 11,96±0,74; PI: 11,47±0,74). Concluiu-se que há uma relação entre os níveis mais elevados de estresse percebido, resistência à insulina e ocorrência da doença periodontal durante a gravidez. Este estudo enfatiza a importância de prevenir a periodontite, a fim de evitar a resistência à insulina e estresse durante a gravidez, uma vez que estes podem causar complicações sistêmicas para a mãe e para o feto.

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AIMS: The fetal programming hypothesis suggests that intrauterine stimuli can induce metabolic changes in offspring, increasing the disease risk in adulthood. Periodontal disease may enhance serum cytokine levels. Cytokines such as tumor necrosis factor-alpha (TNF-α) have been associated with reduced glucose transporter type 4 (GLUT4) expression, decreased protein kinase B (Akt) phosphorylation, and insulin resistance. This study aimed to evaluate GLUT4 content, and Akt serine phosphorylation status in the gastrocnemius skeletal muscle (GSM), glycemia, insulinemia and change in body weight in offspring of rats with periodontal disease. MAIN METHODS: Female Wistar rats were distributed into a control group (CN) and an experimental periodontal disease group (PD), in which a ligature was placed around the mandibular first molars. Seven days after ligature placement, both groups were mated with normal male rats. The ligatures remained throughout pregnancy until weaning, after which the male offspring were distributed into groups: CN-o, control rat offspring; and PD-o, periodontal disease rat offspring. The body weight from 0 to 75days of age was measured. At 75days, the glycemia, insulinemia, TNF-α levels, Akt serine phosphorylation, and GLUT4 content in the GSM were measured in the offspring. KEY FINDINGS: The PD-o group showed a low birth weight (LBW), unchanged glycemia, increased insulinemia, insulin resistance, increased TNF-α levels, decreased Akt serine phosphorylation status, and reduced GLUT4 content in the plasma membrane and translocation index after insulin stimulation. SIGNIFICANCE: Maternal periodontal disease causes LBW, insulin resistance, and alterations in the final stage of insulin signaling in the GSM of adult offspring.

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Osteoporosis is a systemic disease characterized by bone degradation and decreased bone mass that promotes increased bone fragility and eventual fracture risk. Studies have investigated the use of sodium fluoride (NaF) for the treatment of osteoporosis. However, fluoride can alter glucose homeostasis. The aim of this study was to evaluate the effects of NaF intake (50 mg/L) from water on the following parameters of ovariectomized (OVX) rats: (1) tyrosine phosphorylation status of insulin receptor substrate (pp185 (IRS-1/IRS-2)) in white adipose tissue; (2) insulin sensitivity; (3) plasma concentrations of glucose, insulin, total cholesterol, triglyceride, TNF-α, IL-6, osteocalcin, calcium, and fluoride; (4) bone density and biomechanical properties in the tibia; and (5) tibia histomorphometric analysis. Fifty-two Wistar rats (2 months old) were ovariectomized and distributed into two groups: control group (OVX-C) and NaF group (OVX-F), which was subjected to treatment with NaF (50 mg/L) administered in drinking water for 42 days. The chronic treatment with NaF promoted (1) a decrease in pp185 (IRS-1/IRS-2) tyrosine phosphorylation status after insulin infusion in white adipose tissue and in insulin sensitivity; (2) an increase in the plasma concentration of insulin, fluoride, osteocalcin, calcium, triglyceride, VLDL-cholesterol, TNF-α, and IL-6; (3) a reduction in the trabecular width, bone area, stiffness, maximum strength, and tenacity; (4) no changes in body weight, food and water intake, plasma glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, bone mineral content, and bone mineral density. It was concluded that chronic treatment with NaF (50 mg/L) in OVX rats causes a decrease in insulin sensitivity, insulin signaling transduction, and biochemical, biomechanical, and histomorphometric bone parameters.

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OBJECTIVES: Periapical lesion (PL) promotes insulin resistance; however, the mechanisms underlying this alteration are not fully understood. Therefore, in this study, we aimed to evaluate the Akt serine phosphorylation status and GLUT4 expression levels in the gastrocnemius muscle (GM) of rats with PL. MATERIALS AND METHODS: Male Wistar rats (n = 42) were distributed equally into control (CN) and PL groups. The pulpal tissue of the PL group rats was exposed to the oral environment for 30 days. Thereafter, glucose and insulin levels were assessed, followed by homeostasis model assessment of insulin resistance (HOMA-IR). The Akt serine phosphorylation and GLUT4 levels of microsomal (M) and plasma membrane (PM) fractions were evaluated by western blotting and analyzed statistically. RESULTS: Compared to CN group rats, PL group rats had lower insulin sensitivity (as observed by HOMA-IR), lower Akt serine phosphorylation status after insulin stimulus, and lower GLUT4 levels in the PM fraction. However, the M fraction in the PL group did not differ significantly from that of the CN group. CONCLUSIONS: PL decreases insulin sensitivity, Akt phosphorylation, and PM GLUT4 content. CLINICAL RELEVANCE: The present study indicates that preventing endodontic disease can thwart insulin resistance.

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A hipótese da programação fetal sugere que estímulos ou agressões durante a vida intrauterina podem resultar em alterações permanentes na fisiologia e metabolismo da descendência, aumentando o risco de doenças na vida adulta. Estudos demonstraram que tanto a doença periodontal (DP) como o aumento do tecido adiposo elevam a concentração plasmáticas de citocinas. E citocinas, como por exemplo, o TNF-, têm sido relacionadas com a redução da expressão de GLUT4 e resistência à insulina. Sabendo que o GLUT4 é importante para homeostase glicídica, o objetivo do presente estudo foi avaliar em ratos, proles de ratas com doença periodontal ao nascimento, a massa corpórea, e na vida adulta: 1) massa corpórea ao longo de 75 dias de idade; 2) o conteúdo da proteína transportadora de glicose GLUT4 e o seu índice de translocação em tecido muscular esquelético gastrocnêmio (MG); 3) o grau de fosforilação em serina da Akt em MG. As ratas foram distribuidas em dois grupos: a) com doença periodontal (DP), no qual esta doença foi induzida por meio de ligadura com fio de seda ao redor do 1º molar inferior de ambos os lados; b) ratas controle (CN). Após 7 dias da colocação da ligadura, as ratas de ambos os grupos foram colocadas para acasalamento, verificou-se diariamente, por esfregaço vaginal, o dia da copulação. As ratas prenhas foram separadas em caixas individuais. A massa corpórea da prole foi avaliada ao nascimento e durante os 75 dias de idade. Quando os filhotes machos destas ratas completaram 75 dias, realizou-se: 1) dosagem de glicemia e insulinemia; 2) avaliação da proteína transportadora de glicose GLUT4 e seu índice de translocação em MG; 3) avaliação do grau de fosforilação em serina da Akt em MG. Os resultados demonstraram que a doença periodontal materna promove em sua prole ao nascimento baixo peso e na vida adulta: 1) nenhuma alteração nas concentrações plasmáticas de glicose; 2) aumento nas concentrações plasmáticas de insulina; 3) redução na sensibilidade..

The fetal programming hypothesis suggests that intrauterine stimuli or aggression can induce metabolic and physiology changes in offspring, increasing the diseases risk in adulthood. Studies have demonstrated that periodontal disease (PD) and adipose tissue augmentation enhance the cytokines levels. Cytokines such as TNF-α have been associated with reduced GLUT4 expression and insulin resistance. Knowing that GLUT4 is important for glucose homeostasis, the aim of present study was to evaluate in adult rats, offspring of rats with periodontal disease: 1) birth weight and during the 75 days of age; 2) GLUT4 content and its translocation index in gastrocnemius skeletal muscle tissue (GM); 3) Akt serine phosphorylation status in MG. Female Wistar rats were distributed into a control group (CN, n = 4) and a experimental periodontal disease group (PD, n = 4), in which the disease is induced by ligation with silk thread around the 1st molar. Seven days after ligature placement, animals from both groups mated and daily vaginal smears were taken to verify the presence of sperm. Pregnant rats were kept in individual cages. The body weights of the offspring were measured once weekly from birth until 75 days of age. When male offspring of these rats completed 75 days, the experiments were performed: 1) assessment of plasma concentrations of glucose and insulin; 2) evaluation of the GLUT4 content and its translocation index in GM; 3) Akt serine phosphorylation status in GM. The results showed that maternal periodontal disease causes in their offspring low birth weight, and in adulthood: 1) no changes in glycemia; 2) increase in insulinemia; 3) insulin resistance; 4) decrease in GLUT4 content in the plasma membrane and its translocation index in GM; 5) reduction in the Akt serine phosphorylation status in GM. Therefore, we can conclude that maternal periodontal disease causes low birth weight and alterations in the final stage of insulin signaling in skeletal muscle of...

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