Autophagy in periodontitis patients and gingival fibroblasts: unraveling the link between chronic diseases and inflammation.

BACKGROUND: Periodontitis, the most prevalent chronic inflammatory disease, has been related to cardiovascular diseases. Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway. The aim of this research was to study the role of autophagy in peripheral blood mononuclear cells from patients with periodontitis and gingival fibroblasts treated with a lipopolysaccharide of Porphyromonas gingivalis. Autophagy-dependent mechanisms have been proposed in the pathogenesis of inflammatory disorders and in other diseases related to periodontitis, such as cardiovascular disease and diabetes. Thus it is important to study the role of autophagy in the pathophysiology of periodontitis. METHODS: Peripheral blood mononuclear cells from patients with periodontitis (n = 38) and without periodontitis (n = 20) were used to study autophagy. To investigate the mechanism of autophagy, we evaluated the influence of a lipopolysaccharide from P. gingivalis in human gingival fibroblasts, and autophagy was monitored morphologically and biochemically. Autophagosomes were observed by immunofluorescence and electron microscopy. RESULTS: We found increased levels of autophagy gene expression and high levels of mitochondrial reactive oxygen species production in peripheral blood mononuclear cells from patients with periodontitis compared with controls. A significantly positive correlation between both was observed. In human gingival fibroblasts treated with lipopolysaccharide from P. gingivalis, there was an increase of protein and transcript of autophagy-related protein 12 (ATG12) and microtubule-associated protein 1 light chain 3 alpha LC3. A reduction of mitochondrial reactive oxygen species induced a decrease in autophagy whereas inhibition of autophagy in infected cells increased apoptosis, showing the protective role of autophagy. CONCLUSION: Results from the present study suggest that autophagy is an important and shared mechanism in other conditions related to inflammation or alterations of the immune system, such as periodontitis.

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Mitochondrial dysfunction promoted by Porphyromonas gingivalis lipopolysaccharide as a possible link between cardiovascular disease and periodontitis.

Oxidative stress is one of the factors that could explain the pathophysiological mechanism of inflammatory conditions that occur in cardiovascular disease (CVD) and periodontitis. Such inflammatory response is often evoked by specific bacteria, as the lipopolysaccharide (LPS) of Porphyromonas gingivalis is a key factor in this process. The aim of this research was to study the role of mitochondrial dysfunction in peripheral blood mononuclear cells (PBMCs) from periodontitis patients and to evaluate the influence of LPS on fibroblasts to better understand the pathophysiology of periodontitis and its relationship with CVD. PBMCs from patients showed lower CoQ10 levels and citrate synthase activity, together with high levels of ROS production. LPS-treated fibroblasts provoked increased oxidative stress and mitochondrial dysfunction by a decrease in mitochondrial protein expression, mitochondrial mass, and mitochondrial membrane potential. Our study supports the hypothesis that LPS-mediated mitochondrial dysfunction could be at the origin of oxidative stress in periodontal patients. Abnormal PBMC performance may promote oxidative stress and alter cytokine homeostasis. In conclusion, mitochondrial dysfunction could represent a possible link to understanding the interrelationships between two prominent inflammatory diseases: periodontitis and CVD.

La disfunción mitocondrial en la fibromialgia y su implicación en la patogénesis de la enfermedad / Mitochondrial dysfunction in fibromyalgia and its implication in the pathogenesis of disease

La fibromialgia (FM) es un síndrome de dolor crónico generalizado de etiología desconocida. Recientes estudios han mostrado evidencias sobre el papel que podría tener el estrés oxidativo en la fisiopatología de la FM, pero aún no está claro si es la causa o el efecto de las anormalidades observadas en esta. Además, se desconoce la función de la mitocondria en la fisiopatología de la enfermedad, sin embargo, se han observado signos de alteración mitocondrial en esta. Se sabe que la mitocondria es una importante productora de especies reactivas de oxígeno, por lo que se la ha relacionado con el mecanismo patogénico de numerosas enfermedades, incluida la FM. A este respecto, se ha observado que los tratamientos con antioxidantes podrían ser beneficiosos para mejorar el funcionamiento mitocondrial. Por tanto, la disfunción mitocondrial abre un gran campo de investigación terapéutica, por lo que se debería empezar a considerar en la medicina clínica el abordaje de la FM mediante tratamiento con antioxidantes y fármacos relacionados con la biogénesis mitocondrial (AU)

Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology. Recent studies have shown evidence demonstrating that oxidative stress may have a role in the pathophysiology of FM, however it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in FM. Furthermore, it is also controversial the role of mitochondria in the pathophysiology of FM, however signs associated with mitochondrial dysfunction have been observed in FM. Mitochondria are also known to be strong producers of ROS, so have been related with the pathogenic mechanism of numerous diseases including FM. To this respect, it has been observed antioxidants therapies might be beneficial to improve the mitochondrial performance. Therefore, the dysfunction mitochondrial opens a great field of therapeutic research, for what it should start considering in the clinical medicine the boarding of the FM by means of therapy with antioxidant and drugs related to the mitochondrial biogenesis (AU)

[Mitochondrial dysfunction in fibromyalgia and its implication in the pathogenesis of disease]. / La disfunción mitocondrial en la fibromialgia y su implicación en la patogénesis de la enfermedad.

Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology. Recent studies have shown evidence demonstrating that oxidative stress may have a role in the pathophysiology of FM, however it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in FM. Furthermore, it is also controversial the role of mitochondria in the pathophysiology of FM, however signs associated with mitochondrial dysfunction have been observed in FM. Mitochondria are also known to be strong producers of ROS, so have been related with the pathogenic mechanism of numerous diseases including FM. To this respect, it has been observed antioxidants therapies might be beneficial to improve the mitochondrial performance. Therefore, the dysfunction mitochondrial opens a great field of therapeutic research, for what it should start considering in the clinical medicine the boarding of the FM by means of therapy with antioxidant and drugs related to the mitochondrial biogenesis.

Bajos valores de serotonina en suero se correlacionan con la gravedad de los síntomas de la fibromialgia / Low levels of serotonin in serum correlates with severity of fibromyalgia

Objetivo: La fibromialgia es un síndrome de dolor crónico generalizado de etiología desconocida, que afecta predominantemente a mujeres. Dentro de las hipótesis que se han descrito como posibles mecanismos etiopatogénicos destaca la alteración de los valores y metabolismo de la serotonina y su relación con los síntomas en la fibromialgia. El objetivo del presente estudio fue demostrar si existía una correlación entre valores bajos de serotonina y los síntomas de la fibromialgia. Pacientes y método: Se determinó la concentración de serotonina sérica mediante enzimoinmunoensayo en una muestra de 38 pacientes y 25 sujetos sanos. Se correlacionaron los resultados con los síntomas relacionados con el dolor, la depresión, el impacto de la enfermedad (mediante el test Fibromyalgia Impact Questionnaire [FIQ]) y la edad de las pacientes. Resultados: Las pacientes presentaban un descenso de los valores de serotonina de un 45% respecto a los sujetos sanos. Se observó correlación con los parámetros predeterminados de dolor, depresión, FIQ y edad.Conclusión: Los valores de serotonina correlacionan con la gravedad de la fibromialgia. Además, existe una relación entre la edad y el descenso de la serotonina (AU)

Objetive: Fibromyalgia (FM) is a chronic pain syndrome of unknown etiology, which affects predominantly women. Among the alterations that have been implicated in the pathophysiology of FM, there have been postulated disturbances in serotonin levels and metabolism, and their implication in symptoms. The aim of the present study was to assess the correlation levels between low levels of serotonin and severity of symptoms in FM. Patients and methods: We determined serotonin levels using an ELISA kit in serum from 38 FM patients and 25 healthy individual. Results were correlated with symptoms regarding pain, depression, impact of disease (FIQ) and age. Results: Serotonin levels were decreased by 45% compared to healthy individual. An important correlation was observed between serotonin levels and predetermined parameters of pain, depression, FIQ and age. Conclusion: Serotonin levels are correlated with severity of FM. In addition, there is an interesting correlation between serotonin levels and age of patients (AU)

Acute oxidant damage promoted on cancer cells by amitriptyline in comparison with some common chemotherapeutic drugs.

Oxidative therapy is a relatively new anticancer strategy based on the induction of high levels of oxidative stress, achieved by increasing intracellular reactive oxygen species (ROS) and/or by depleting the protective antioxidant machinery of tumor cells. We focused our investigations on the antitumoral potential of amitriptyline in three human tumor cell lines: H460 (lung cancer), HeLa (cervical cancer), and HepG2 (hepatoma); comparing the cytotoxic effect of amitriptyline with three commonly used chemotherapeutic drugs: camptothecin, doxorubicin, and methotrexate. We evaluated apoptosis, ROS production, mitochondrial mass and activity, and antioxidant defenses of tumor cells. Our results show that amitriptyline produces the highest cellular damage, inducing high levels of ROS followed by irreversible serious mitochondrial damage. Interestingly, an unexpected decrease in antioxidant machinery was observed only for amitriptyline. In conclusion, based on the capacity of generating ROS and inhibiting antioxidants in tumor cells, amitriptyline emerges as a promising new drug to be tested for anticancer therapy.

[Low levels of serotonin in serum correlates with severity of fibromyalgia]. / Bajos valores de serotonina en suero se correlacionan con la gravedad de los síntomas de la fibromialgia.

OBJECTIVE: Fibromyalgia (FM) is a chronic pain syndrome of unknown etiology, which affects predominantly women. Among the alterations that have been implicated in the pathophysiology of FM, there have been postulated disturbances in serotonin levels and metabolism, and their implication in symptoms. The aim of the present study was to assess the correlation levels between low levels of serotonin and severity of symptoms in FM. PATIENTS AND METHODS: We determined serotonin levels using an ELISA kit in serum from 38 FM patients and 25 healthy individual. Results were correlated with symptoms regarding pain, depression, impact of disease (FIQ) and age. RESULTS: Serotonin levels were decreased by 45% compared to healthy individual. An important correlation was observed between serotonin levels and predetermined parameters of pain, depression, FIQ and age. CONCLUSION: Serotonin levels are correlated with severity of FM. In addition, there is an interesting correlation between serotonin levels and age of patients.