Naringenin attenuates cerebral ischemia/reperfusion injury by inhibiting oxidative stress and inflammatory response via the activation of SIRT1/FOXO1 signaling pathway in vitro

Purpose: To explore the protection of naringenin against oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell injury, a cell model of cerebral ischemia/reperfusion (I/R) injury in vitro, focusing on SIRT1/FOXO1 signaling pathway. Methods: Cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, malondialdehyde (MDA) content, 4-hydroxynonenoic acid (4-HNE) level, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured by commercial kits. Inflammatory cytokines levels were determined by enzyme-linked immunosorbent assay (ELISA). The protein expressions were monitored by Western blot analysis. Results: Naringenin significantly ameliorated OGD/Rinduced cytotoxicity and apoptosis in HT22 cells. Meanwhile, naringenin promoted SIRT1 and FOXO1 protein expressions in OGD/R-subjected HT22 cells. In addition, naringenin attenuated OGD/R-induced cytotoxicity, apoptosis, oxidative stress (the increased ROS, MDA and 4-HNE levels, and the decreased SOD, GSH-Px and CAT activities) and inflammatory response (the increased tumor necrosis factor-α, interleukin [IL]-1ß, and IL-6 levels and the decreased IL-10 level), which were blocked by the inhibition of the SIRT1/FOXO1 signaling pathway induced by SIRT1-siRNA transfection. Conclusion: Naringenin protected HT22 cells against OGD/R injury depending on its antioxidant and anti-inflammatory activities via promoting the SIRT1/FOXO1 signaling pathway.

Canine atopic dermatitis: systemic immunomodulatory protocol based on clinical phenotype / Dermatite atópica canina: protocolos imunomodulatórios sistêmicos baseados no fenótipo clínico

Canine atopic dermatitis (cAD) is a multifactorial allergic disease associated with immune dysfunction and abnormal skin barrier. Several immunological mediators play a role in its pathogenesis. Such molecules are produced by the activation of T helper lymphocytes (Th) through polarization to Th1 and/or Th2, which contributes to different lesion patterns. Acute lesions are mediated by an activation of the Th2 cytokine axis, which clinically induces erythema and pruritus. Conversely, in chronic injuries a mixed immune response of Th1/Th2 cytokines occurs, leading to hyperpigmented and lichenified skin. The clinical understanding of these patterns and the mode of action of immunomodulators are crucial for the best clinical management of the atopic patient. In this context, this review discussed the role of the immune response and the immunomodulatory drugs in dogs with atopic dermatitis and suggested a therapeutic protocol based on clinical phenotype. Based on the evidences showed in this review, it is considered appropriate to use immunomodulatory drugs that target cytokine spectrum related with the clinical phenotype of cAD.

A dermatite atópica canina (DAC) é uma doença alérgica multifatorial associada à disfunção imune e barreira cutânea anormal. Vários mediadores imunológicos desempenham um papel na sua patogênese. Tais moléculas são produzidas pela ativação de linfócitos T auxiliares (Th) por meio da polarização para Th1 e/ou Th2, o que contribui para diferentes padrões de lesão. Lesões agudas são mediadas pela ativação do eixo de citocinas Th2, que clinicamente induz eritema e prurido. Por outro lado, nas lesões crônicas ocorre uma resposta imune mista de citocinas Th1/Th2, levando à pele hiperpigmentada e liquenificada. O entendimento clínico desses padrões e o modo de ação dos imunomoduladores são cruciais para o melhor manejo clínico do paciente atópico. Esta revisão visa discutir o papel da resposta imune e das drogas imunomoduladoras em cães com dermatite atópica e sugerir um protocolo terapêutico baseado no fenótipo clínico. Baseado nas evidências apresentadas nessa revisão, é considerado apropriado utilizar drogas imunomoduladoras que abrangem o espectro de citocinas relacionadas ao fenótipo clínico da DAC.

Tarantula cubensis extract (Theranekron®) inhibits inflammation in carrageenan-induced acute paw edema in rats / [Extrato de tarântula cubensis (Theranekron®) inibe a inflamação no edema induzido por algas vermelhas na pata de ratos]

The aim of this study was to investigate the anti-inflammatory effect of alcoholic extract of Tarantula cubensis alcoholic extract (TCAE) in experimentally induced inflammation in rats. Fifty-four adult Sprague-Dawley male rats were randomly divided into nine groups. Paw edema was induced by 0.2mL subplantar (s.p.) injection of 1% carrageenan (CAR) into the right hind paw. Rats were treated with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (INDO) (10mg/kg, p.o.) or TCAE at different doses (1, 10 or 100µg/kg) injected s.c. for systemic or s.p. for local anti-inflammatory effect. Saline was used as control. Changes in paw thickness, volume, and weight were calculated as percentages. Formalin-fixed paws were used for histopathological examination. We detected that TCAE applied s.c. at 10µg/kg and 100µg/kg doses resulted in thinner paw thickness, lower paw volume, and lower paw weights four hours after the induction of inflammation when compared with the INDO group (p<0.05). The paw edema inhibitory effect of TCAE applied at a dose of 10µg/kg, s.c. was 68% when compared with the INDO which had an inhibitory effect of 56%. These results were verified with similar histopathological findings. The anti-inflammatory feature of 10µg/kg of TCAE given systematically was similar to the effects of INDO. Our results suggest that TCAE has anti-inflammatory effects by reducing edema and decreasing inflammatory reaction. These results may be attributed to the inhibition of the production of proinflammatory mediators. Thus, TCAE may be considered as a potential anti-inflammatory agent for treating acute inflammatory conditions.

O objetivo deste estudo foi investigar o efeito anti-inflamatório do extrato alcoólico de Tarantula cubensis (TCAE) na inflamação induzida experimentalmente em ratos. Cinqüenta e quatro ratos Sprague-Dawley adultos machos foram divididos aleatoriamente em nove grupos. O edema da pata foi induzido pela injeção de 0,2mL de subplantar (s.p.) de 1% de carragena (CAR) na pata traseira direita. Ratos foram tratados com o medicamento antiinflamatório não esteróide (NSAID) indometacina (INDO) (10mg/kg, p.o.) ou TCAE em doses diferentes (1, 10 ou 100µg/kg) injetado s.c. para efeito sistêmico ou s.p. para efeito antiinflamatório local. A soro fisiológico foi usado como controle. As mudanças na espessura da pata, volume e peso foram calculadas como porcentagens. As patas fixadas com fórmalina foram usadas para exame histopatológico. Detectamos que o TCAE aplicado s.c. em doses de 10µg/kg e 100µg/kg resultou em menor espessura da pata, menor volume da pata e menor peso da pata quatro horas após a indução da inflamação quando comparado com o grupo INDO (p<0,05). O efeito inibidor do edema da pata de TCAE aplicado na dose de 10µg/kg, s.c. foi de 68% quando comparado com o INDO que teve um efeito inibidor de 56%. Estes resultados foram verificados com resultados histopatológicos semelhantes. A característica anti-inflamatória de 10µg/kg de TCAE dada sistematicamente foi semelhante aos efeitos do INDO. Nossos resultados sugerem que o TCAE tem efeitos anti-inflamatórios reduzindo o edema e diminuindo a reação inflamatória. Estes resultados podem ser atribuídos à inibição da produção de mediadores pró-inflamatórios. Assim, o TCAE pode ser considerado como um agente antiinflamatório potencial para o tratamento de condições inflamatórias agudas.

The ethanol extract of Periplaneta Americana L. improves ulcerative colitis induced by a combination of chronic stress and TNBS in rats

Purpose: To investigate the effects of Periplaneta americana L. on ulcerative colitis (UC) induced by a combination of chronic stress (CS) and 2,4,6-trinitrobenzene sulfonic acid enema (TNBS) in rats. Methods: The experiment UC model with CS was established in rats by a combination of chronic restraint stress, excess failure, improper, and TNBS. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS) and pro-inflammatory mediators were measured. The content of corticotropin-releasing hormone (CRH) in hypothalamus or adrenocorticotropic hormone (ACTH) and corticosteroids (CORT) in plasma were evaluated by enzyme-linked immunosorbent assay. The proportion of T lymphocyte subsets was detected by flow cytometry, and gut microbiota was detected by 16S rDNA amplicon sequencing. Results: Weight loss, DAI, CMDI, HS and proinflammatory mediators were reversed in rats by P. americana L. treatment after UC with CS. Increased epidermal growth factor (EGF) was observed in P. americana L. groups. In addition, P. americana L. could reduce the content of CRH and ACTH and regulate the ratio of CD3+, CD3+CD8+ and CD3+CD4+CD25+/CD4+ in spleen. Comparably, P. americana L. changes composition of gut microbiota. Conclusions: The ethanol extract of Periplaneta Americana L. improves UC induced by a combination of CS and TNBS in rats.

Inflammation: improving understanding to prevent or ameliorate kidney diseases

Abstract Inflammatory processes are believed to play an important role in immune response to maintain tissue homeostasis by activating cellular signaling pathways and releasing inflammatory mediators in the injured tissue. Although acute inflammation can be considered protective, an uncontrolled inflammation may evolve to tissue damage, leading to chronic inflammatory diseases. Inflammation can be considered the major factor involved in the pathological progression of acute and chronic kidney diseases. Functional characteristics of this organ increase its vulnerability to developing various forms of injuries, including acute kidney injury (AKI) and chronic kidney disease (CKD). In view of translational research, several discoveries should be considered regarding the pathogenesis of the inflammatory process, which results in the validation of biomarkers for early detection of kidney diseases. Biomarkers enable the identification of proinflammatory mediators in kidney affections, based on laboratory research applied to clinical practice. Some inflammatory molecules can be useful biomarkers for the detection and diagnosis of kidney diseases, such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and interleukin 18.

Effects of venoms on neutrophil respiratory burst: a major inflammatory function

Neutrophils play a pivotal role in innate immunity and in the inflammatory response. Neutrophils are very motile cells that are rapidly recruited to the inflammatory site as the body first line of defense. Their bactericidal activity is due to the release into the phagocytic vacuole, called phagosome, of several toxic molecules directed against microbes. Neutrophil stimulation induces release of this arsenal into the phagosome and induces the assembly at the membrane of subunits of the NAPDH oxidase, the enzyme responsible for the production of superoxide anion that gives rise to other reactive oxygen species (ROS), a process called respiratory burst. Altogether, they are responsible for the bactericidal activity of the neutrophils. Excessive activation of neutrophils can lead to extensive release of these toxic agents, inducing tissue injury and the inflammatory reaction. Envenomation, caused by different animal species (bees, wasps, scorpions, snakes etc.), is well known to induce a local and acute inflammatory reaction, characterized by recruitment and activation of leukocytes and the release of several inflammatory mediators, including prostaglandins and cytokines. Venoms contain several molecules such as enzymes (phospholipase A2, L-amino acid oxidase and proteases, among others) and peptides (disintegrins, mastoporan, parabutoporin etc.). These molecules are able to stimulate or inhibit ROS production by neutrophils. The present review article gives a general overview of the main neutrophil functions focusing on ROS production and summarizes how venoms and venom molecules can affect this function.(AU)

Effects of venoms on neutrophil respiratory burst: a major inflammatory function

Neutrophils play a pivotal role in innate immunity and in the inflammatory response. Neutrophils are very motile cells that are rapidly recruited to the inflammatory site as the body first line of defense. Their bactericidal activity is due to the release into the phagocytic vacuole, called phagosome, of several toxic molecules directed against microbes. Neutrophil stimulation induces release of this arsenal into the phagosome and induces the assembly at the membrane of subunits of the NAPDH oxidase, the enzyme responsible for the production of superoxide anion that gives rise to other reactive oxygen species (ROS), a process called respiratory burst. Altogether, they are responsible for the bactericidal activity of the neutrophils. Excessive activation of neutrophils can lead to extensive release of these toxic agents, inducing tissue injury and the inflammatory reaction. Envenomation, caused by different animal species (bees, wasps, scorpions, snakes etc.), is well known to induce a local and acute inflammatory reaction, characterized by recruitment and activation of leukocytes and the release of several inflammatory mediators, including prostaglandins and cytokines. Venoms contain several molecules such as enzymes (phospholipase A2, L-amino acid oxidase and proteases, among others) and peptides (disintegrins, mastoporan, parabutoporin etc.). These molecules are able to stimulate or inhibit ROS production by neutrophils. The present review article gives a general overview of the main neutrophil functions focusing on ROS production and summarizes how venoms and venom molecules can affect this function.(AU)

Once upon a time, inflammation

Inflammation has accompanied humans since their first ancestors appeared on Earth. Aulus Cornelius Celsus (25 BC-50 AD), a Roman encyclopedist, offered a still valid statement about inflammation: "Notae vero inflammationis sunt quatuor: rubor et tumor cum calore and dolore", defining the four cardinal signs of inflammation as redness and swelling with heat and pain. While inflammation has long been considered as a morbid phenomenon, John Hunter (18th century) and Elie Metchnikoff (19th century) understood that it was a natural and beneficial event that aims to address a sterile or an infectious insult. Many other famous scientists and some forgotten ones have identified the different cellular and molecular players, and deciphered the different mechanisms of inflammation. This review pays tribute to some of the giants who made major contributions, from Hippocrates to the late 19th and first half of the 20th century. We particularly address the discoveries related to phagocytes, diapedesis, chemotactism, and fever. We also mention the findings of the various inflammatory mediators and the different approaches designed to treat inflammatory disorders.(AU)

Once upon a time, inflammation

Inflammation has accompanied humans since their first ancestors appeared on Earth. Aulus Cornelius Celsus (25 BC-50 AD), a Roman encyclopedist, offered a still valid statement about inflammation: "Notae vero inflammationis sunt quatuor: rubor et tumor cum calore and dolore", defining the four cardinal signs of inflammation as redness and swelling with heat and pain. While inflammation has long been considered as a morbid phenomenon, John Hunter (18th century) and Elie Metchnikoff (19th century) understood that it was a natural and beneficial event that aims to address a sterile or an infectious insult. Many other famous scientists and some forgotten ones have identified the different cellular and molecular players, and deciphered the different mechanisms of inflammation. This review pays tribute to some of the giants who made major contributions, from Hippocrates to the late 19th and first half of the 20th century. We particularly address the discoveries related to phagocytes, diapedesis, chemotactism, and fever. We also mention the findings of the various inflammatory mediators and the different approaches designed to treat inflammatory disorders.(AU)

Inflammation: improving understanding to prevent or ameliorate kidney diseases

Inflammatory processes are believed to play an important role in immune response to maintain tissue homeostasis by activating cellular signaling pathways and releasing inflammatory mediators in the injured tissue. Although acute inflammation can be considered protective, an uncontrolled inflammation may evolve to tissue damage, leading to chronic inflammatory diseases. Inflammation can be considered the major factor involved in the pathological progression of acute and chronic kidney diseases. Functional characteristics of this organ increase its vulnerability to developing various forms of injuries, including acute kidney injury (AKI) and chronic kidney disease (CKD). In view of translational research, several discoveries should be considered regarding the pathogenesis of the inflammatory process, which results in the validation of biomarkers for early detection of kidney diseases. Biomarkers enable the identification of proinflammatory mediators in kidney affections, based on laboratory research applied to clinical practice. Some inflammatory molecules can be useful biomarkers for the detection and diagnosis of kidney diseases, such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and interleukin 18.(AU)