Octyl gallate decrease lymphocyte activation and regulates neutrophil extracellular traps release.

BACKGROUND: Inflammation is a complex mechanism with an objective to destroy and eliminate the invading microorganisms. During acute inflammation, the neutrophils are the major cells involved in this process and, although they defend the organism, must die to not generate damage. The two major mechanisms that drive neutrophils to death are: apoptosis and a novel mechanism recently discovered denominated NETosis. This process is a "suicidal mechanism", in which the cells release "neutrophil extracellular traps" (NETs) during the inflammatory response. Octyl gallate (OG) is one of the gallic acid derivates, with several protective effects, such as antioxidant and anti-inflammatory in cancer models. Thus, this study aimed to investigate the action of OG on the proliferation of lymphocytes, neutrophils activation, and its effectiveness in an experimental sepsis model. METHODS: Lymphocytes and neutrophils were obtained from healthy donors. Cell viability, apoptosis, NETs release and antioxidant capacity of OG were observed. In addition, survival was evaluated in an experimental model of sepsis in C57BL/6 mice. RESULTS: Our study demonstrated, for the first time, that the OG can act as an inhibitor of reactive oxygen species (ROS) release, NETs formation in primary human neutrophils and, modulates the lipopolysaccharide (LPS) effect in neutrophil apoptosis. The OG also inhibited peripheral blood mononuclear cells (PBMCs) proliferation in vitro. Despite the positive results, we did not observe an increase in the survival of septic animals. CONCLUSIONS: The pharmacological potential of OG, modulating activation of neutrophils and lymphocytes, suggests the use as an adjuvant therapeutic strategy in inflammatory diseases.

Impact of maternal physical exercise on inflammatory and hypothalamic-pituitary-adrenal axis markers in the brain and lungs of prenatally stressed neonatal mice.

This study aimed to evaluate the effects of maternal exercise on alterations induced by prenatal stress in markers of the inflammatory process and the hypothalamic-pituitary-adrenal axis in the brain and lungs of neonatal mice. Female Balb/c mice were divided into three groups: control, prenatal restraint stress, prenatal restraint stress and physical exercise before and during the gestational period. On day 0 (PND0) and 10 (PND10), mice were euthanized for brain and lung analyses. The gene expression of GR, MR, IL-6, IL-10, and TNF in the brain and lungs and the protein expression of MMP-2 in the lungs were analyzed. Maternal exercise reduced IL-6 and IL-10 gene expression in the brain of PND0 mice. Prenatal stress and maternal exercise decreased GR, MR, IL-6, and TNF gene expression in the lungs of PND0 mice. In the hippocampus of PND10 females, exercise inhibited the effects of prenatal stress on the expression of MR, IL-6, and IL-10. In the lungs of PND10 females, exercise prevented the decrease in GR expression caused by prenatal stress. In the hippocampus and lungs of PND10 males, prenatal stress decreased GR gene expression. Our findings confirm the effects induced by prenatal stress and demonstrate that physical exercise before and during the gestational period may have a protective role on inflammatory changes.

Resveratrol increases the activation markers and changes the release of inflammatory cytokines of hepatic stellate cells.

The phytoalexin Resveratrol (3,5,4'-trihydroxystilbene; RSV) has been related to numerous beneficial effects on health by its cytoprotection and chemoprevention activities. Liver fibrosis is characterized by the extracellular matrix accumulation after hepatic injury and can lead to cirrhosis. Hepatic stellate cells (HSC) play a crucial role during fibrogenesis and liver wound healing by changing their quiescent phenotype to an activated phenotype for protecting healthy areas from damaged areas. Strategies on promoting the activated HSC death, the quiescence return or the cellular activation stimuli decrease play an important role on reducing liver fibrosis. Here, we evaluated the RSV effects on some markers of activation in GRX, an HSC model. We further evaluated the RSV influence in the ability of GRX on releasing inflammatory mediators. RSV at 1 and 10 µM did not alter the protein content of α-SMA, collagen I and GFAP; but 50 µM increased the content of these activation-related proteins. Also, RSV did not change the myofibroblast-like morphology of GRX. Interestingly, RSV at 10 and 50 µM decreased the GRX migration and collagen-I gel contraction. Finally, we showed that RSV triggered the increase in the TNF-α and IL-10 content in culture media of GRX while the opposite occurred for the IL-6 content. Altogether, these results suggested that RSV did not decrease the activation state of GRX and oppositely, triggered a pro-activation effect at the 50 µM concentration. However, despite the increase of TNF- α in culture media, these results on IL-6 and IL-10 secretion were in accordance with the anti-inflammatory role of RSV in our model.

Fructose-1,6-bisphosphate induces generation of reactive oxygen species and activation of p53-dependent cell death in human endometrial cancer cells.

Fructose-1,6-bisphosphate (F1,6BP), an intermediate of the glycolytic pathway, has been found to play a promising anticancer effect; nevertheless, the mechanisms involved remain poorly understood. The present study aimed to evaluate the effect and mechanisms of F1,6BP in a human endometrial cancer cell line (Ishikawa). F1,6BP showed an antiproliferative and non-cytotoxic effect on endometrial cancer cells. These effects are related to the increase in reactive oxygen species (ROS) levels and mitochondrial membrane potential (ΔΨm). These harmful stimuli trigger the upregulation of the expression of pro-apoptotic genes (p53 and Bax), leading to the reduction of cell proliferation through inducing programmed cell death by apoptosis. Furthermore, F1,6BP-treated cells had the formation of autophagosomes induced, as well as a decrease in their proliferative capacity after withdrawing the treatment. Our results demonstrate that F1,6BP acts as an anticancer agent through the generation of mitochondrial instability, loss of cell function, and p53-dependent cell death. Thus, F1,6BP proves to be a potential molecule for use in the treatment against endometrial cancer.

Anti-inflammatory effect of octyl gallate in alveolar macrophages cells and mice with acute lung injury.

Acute lung injury (ALI) is an inflammatory process, and has high incidence and mortality. ALI and the acute respiratory distress syndrome are two common complications worldwide that result in acute lung failure, sepsis, and death. Pro-inflammatory substances, such as cytokines and chemokines, are responsible for activating the body's defense mechanisms and usually mediate inflammatory processes. Therefore, the research of substances that decrease the uncontrolled response of organism is seen as potential for patients with ALI. Octyl gallate (OG) is a phenolic compound with therapeutic actions namely antimicrobial, antiviral, and antifungal. In this study, we evaluated its action on lipopolysaccharide (LPS)-activated alveolar macrophages RAW 264.7 cells and ALI in male mice. Our results demonstrated protective effects of OG in alveolar macrophages activated with LPS and mice with ALI. The OG treatment significantly decreased the inflammatory markers in both studies in vitro and in vivo. The data suggested that OG can act as an anti-inflammatory agent for ALI.

CPBMF65, a synthetic human uridine phosphorylase-1 inhibitor, reduces HepG2 cell proliferation through cell cycle arrest and senescence.

Hepatocellular carcinoma (HCC) is the most prevalent type of tumor among primary liver tumors and is the second highest cause of cancer-related deaths worldwide. Current therapies are controversial, and more research is needed to identify effective treatments. A new synthetic compound, potassium 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-olate (CPBMF65), is a potent inhibitor of the human uridine phosphorylase-1 (hUP1) enzyme, which controls the cell concentration of uridine (Urd). Urd is a natural pyrimidine nucleoside involved in cellular processes, such as RNA synthesis. In addition, it is considered a promising biochemical modulator, as it may reduce the toxicity caused by chemotherapeutics without impairing its anti-tumor activity. Thus, the objective of this study is to evaluate the effects of CPBMF65 on the proliferation of the human hepatocellular carcinoma cell line (HepG2). Cell proliferation, cytotoxicity, apoptosis, senescence, autophagy, intracellular Urd levels, cell cycle arrest, and drug resistance were analyzed. Results demonstrate that, after incubation with CPBMF65, HepG2 cell proliferation decreased, mainly through cell cycle arrest and senescence, increasing the levels of intracellular Urd and maintaining cell proliferation reduced during chronic treatment. In conclusion, results show, for the first time, the ability of a hUP1 inhibitor (CPBMF65) to reduce HepG2 cell proliferation through cell cycle arrest and senescence.

Maternal separation induces long-term oxidative stress alterations and increases anxiety-like behavior of male Balb/cJ mice.

Early life stress (ELS) exposure is a well-known risk factor for the development of psychiatric conditions, including anxiety disorder. Preclinical studies show that maternal separation (MS), a classical model of ELS, causes hypothalamic-pituitary-adrenal (HPA) axis alterations, a key contributor to the stress response modulation. Given that HPA axis activation has been shown to induce oxidative stress, it is possible to hypothesize that oxidative stress mediates the relationship between chronic ELS exposure and the development of several disorders. Here, we investigate the effects of MS in the oxidative status [plasma and brain reduced glutathione, catalase and thiobarbituric acid reactive substances (TBARS)], metabolism (glucose, triglycerides and cholesterol) and anxiety-like behaviors in adult Balb/cJ mice. In short, we found that MS increased anxiety-like behaviors in the open field, light/dark test but not in the elevated-plus maze. Animals also presented increased circulating cholesterol, increased TBARS in the plasma and decreased catalase in the hippocampus. Our findings suggest that MS induces long-term alterations in oxidative stress and increased anxiety-like behaviors.

Metabolic dysfunction in a rat model of early-life scarcity-adversity: Modulatory role of cafeteria diet.

NEW FINDINGS: What is the central question of this study? Early-life adversity is associated with increased risk for obesity and metabolic dysfunction. However, it is unclear whether obesity and metabolic dysfunction result from coping strategies to deal with adversity-related emotional dysregulation, a direct programming of systems regulating metabolic function, or a combination of both. What is the main finding and its importance? Early-life adversity increases vulnerability to later-life obesity and metabolic dysfunction, indicating that genetics and adult lifestyle are not the only determinants of obesity and related metabolic dysfunction. Moreover, consumption of cafeteria diet exacerbated metabolic dysfunction associated with early-life adversity, suggesting that poor dietary choices might have a bigger impact in the context of early-life adversity. ABSTRACT: Early-life adversity has become recognized as an important factor contributing to adult obesity and associated metabolic dysfunction. However, it is unclear whether obesity and metabolic dysfunction associated with early-life adversity result from coping strategies to deal with adversity-related emotional dysregulation, a direct programming of systems regulating metabolic function, or a combination. Interestingly, both early-life adversity and later-life dietary choices affect immune function, favouring pro-inflammatory mechanisms that are associated with obesity-related metabolic dysfunction. To investigate the unique and/or interactive effects of early-life adversity and later-life dietary choices for increased vulnerability to obesity and metabolic dysfunction, and specifically the role of the immune system in this vulnerability, we combined a naturalistic rat model of early-life scarcity-adversity with a rat model of obesity, the cafeteria diet. Our results indicate that early-life adversity alone induces insulin resistance, reduces pancreatic insulin secretion, plasma concentrations of triglycerides and cholesterol, and increases fasting glucose and tumour necrosis factor-α plasma concentrations. Importantly, animals exposed to adverse rearing were more vulnerable to metabolic dysregulation associated with the cafeteria diet, given that they consumed more energy, showed more severe hepatic steatosis and increased concentrations of the pro-inflammatory cytokine interleukin-1ß than normally reared animals fed the cafeteria diet. Together, our results suggest that early-life adversity negatively programmes physiological systems that regulate metabolic function and increases vulnerability to obesity and metabolic dysfunction in adulthood. These results highlight the intrinsic relationship between the quality of the early postnatal environment and later-life dietary choices on adult health outcomes.

Mesenchymal stem cells improves survival in LPS-induced acute lung injury acting through inhibition of NETs formation.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of acute hypoxemic respiratory failure resulting from a variety of direct and indirect injuries to the gas exchange parenchyma of the lungs. During the ALI, we have an increase release of proinflammatory cytokines and high reactive oxygen species (ROS) formation. These factors are responsible for the release and activation of neutrophil-derived proteases and the formation of neutrophil extracellular traps (NETs). The excessive increase in the release of NETs cause damage to lung tissue. Recent studies have studies involving the administration of mesenchymal stem cells (MSCs) for the treatment of experimental ALI has shown promising results. In this way, the objective of our study is to evaluate the ability of MSCs, in a lipopolysaccharide (LPS)-induced ALI model, to reduce inflammation, oxidative damage, and consequently decrease the release of NETs. Mice were submitted lung injury induced by intratracheal instillation of LPS and subsequently treated or not with MSCs. Treatment with MSCs was able to modulate pulmonary inflammation, decrease oxidative damage, and reduce the release of NETs. These benefits from treatment are evident when we observe a significant increase in the survival curve in the treated animals. Our results demonstrate that MSCs treatment is effective for the treatment of ALI. For the first time, it is described that MSCs can reduce the formation of NETs and an experimental model of ALI. This finding is directly related to these cells modulate the inflammatory response and oxidative damage in the course of the pathology.

Mesenchymal stem cells cannot affect mRNA expression of toll-like receptors in different tissues during sepsis.

OBJECTIVE AND DESIGN: Experimental animal models and human clinical studies support a crucial role for TLRs in infectious diseases. The aim of this study was to test the ability of MSCs, which have immunomodulatory effects, of altering the mRNA expression of toll-like receptors during a experimental model of sepsis in different tissues. MATERIALS AND METHODS: Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 106 cells/animal). Lungs, cortex, kidney, liver and colon tissue were dissected after 12 h of sepsis induction and TLR2/3/4/9 mRNA were evaluated by RT-qPCR. RESULTS: We observed a decrease of TLR2 and 9 mRNA expression in the liver of the sepsis group, while TLR3 was decreased in the lung and liver. No change was found between the sepsis group and the sepsis + MSC group. CONCLUSIONS: In this model of experimental sepsis the MSCs were unable to modify the mRNA expression of the different toll-like receptors evaluated.

Fructose-1,6-bisphosphate reverts iron-induced phenotype of hepatic stellate cells by chelating ferrous ions.

Hepatic fibrosis is an extracellular matrix deposition by hepatic stellate cells (HSC). Fibrosis can be caused by iron, which will lead to hydroxyl radical production and cell damage. Fructose-1,6-bisphosphate (FBP) has been shown to deliver therapeutic effects in many pathological situations. In this work, we aimed to test the effects of FBP in HSC cell line, GRX, exposed to an excess of iron (Fe). The Fe-treatment increased cell proliferation and FBP reversed this effect, which was not due to increased necrosis, apoptosis or changes in cell cycle. Oil Red-O staining showed that FBP successfully increased lipid content and lead GRX cells to present characteristics of quiescent HSC. Fe-treatment decreased PPAR-γ expression and increased Col-1 expression. Both effects were reversed by FBP which also decreased TGF-ß1 levels in comparison to both control and Fe groups. FBP, also, did not present scavenger activity in the DPPH assay. The treatment with FBP resulted in decreased proliferation rate, Col-1 expression and TGF-ß1 release by HSC cells. Furthermore, activated PPAR-γ and increased lipid droplets induce cells to become quiescent, which is a key event to reversion of hepatic fibrosis. FBP also chelates iron showing potential to improve Cell redox state.

Mesenchymal stem cells decrease splenocytes apoptosis in a sepsis experimental model.

OBJECTIVE AND DESIGN: Mesenchymal stem cells (MSCs) are potent modulators of immune responses. Sepsis is the association of a systemic inflammatory response with an infection. The aim of this study was to test the ability of MSCs derived from adipose tissue, which have immunomodulatory effects, and to inhibit the septic process in an experimental model of mice. METHODS: Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 10(6) cells/animal). RESULTS: In the control group, there were no deaths; in the untreated septic group, the mortality rate was 100 % within 26 h; in the septic group treated with MSCs, the mortality rate reached 40 % within 26 h. The group treated with MSCs was able to reduce the markers of tissue damage in the liver and pancreas. The treated group had a reduction of inflammatory markers. Furthermore, the MSCs-treated group was able to inhibit the increase of apoptosis in splenocytes observed in the untreated septic group. CONCLUSIONS: Our data showed that MSCs ameliorated the immune response with decrease of inflammatory cytokines and increase anti-inflammatory IL-10; moreover, inhibited splenocytes apoptosis and, consequently, inhibited tissue damage during sepsis.

(+)-Catechin attenuates activation of hepatic stellate cells.

(+)-Catechin is a type of catechin present in large amounts in açaí fruits and cocoa seeds. Besides its antioxidant and anti-inflammatory activities, little is known about its effects in the liver, especially during hepatic fibrosis. We report here the effects of (+)-catechin on hepatic stellate cells. (+)-Catechin induced quiescent phenotype in GRX cells, along with an increase in lipid droplets. Proliferator-activated receptor γ mRNA expression was upregulated, whereas type I collagen mRNA expression was downregulated. Pro-inflammatory cytokines were not influenced by (+)-catechin, whereas the levels of interleukin 10 were significantly increased. The data provide evidence that (+)-catechin can reduce hepatic stellate cell activation.

The potential of circHIPK3 as a biomarker in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by leukocytosis and left shift. The primary molecular alteration is the BCR::ABL1, chimeric oncoprotein with tyrosine kinase activity, responsible for the initial oncogenesis of the disease. Therapy of CML was revolutionized with the advent of tyrosine kinase inhibitors, but it is still not considered curative and may present resistance and serious adverse effects. Discoveries in CML inaugurated a new era in cancer treatment and despite all the advances, a new biomarker is needed to detect resistance and adverse effects. Circular RNAs (circRNAs) are a special type of non-coding RNA formed through a process called backsplicing. The majority of circRNAs are derived from protein-coding genes. CircHIPK3 is formed from the second exon of the HIPK3 gene and has been found in various pathologies, including different types of cancer. New approaches have demonstrated the potential of circular RNAs in cancer research, and circHIPK3 has shown promising results. It is often associated with cellular regulatory pathways, suggesting an important role in the molecular dynamics of tumors. The identification of biomarkers is an important tool for therapeutic improvement; thus we review the role of circHIPK3 and its potential as a biomarker in CML.

Baccharis anomala DC. extract reduces inflammation and attenuates hepatic fibrosis in vivo by decreasing NF-kB and extracellular matrix compounds.

Baccharis anomala DC. (BA) is a plant species found in the tropical regions of South America and is widely used for its hepatoprotective effects, as well as for the treatment of gastrointestinal diseases. Studies have recently reported its antioxidant and anti-inflammatory potential. BA extract can reverse the activated phenotype of hepatic stellate cells (HSC), which plays a central role in extracellular matrix (ECM) deposition in the development of liver fibrosis. Thus, this study aimed to evaluate the effects of the treatment with BA extract on liver fibrosis in a CCl4-induced liver fibrosis model in BALB/c mice. Methanolic extract was obtained from BA leaves, a gas chromatography/mass spectrometry (GC/MS) to detect the compounds present was performed, and then administered by intraperitoneal injection in Balb/C mice at a concentration of 50 and 100 mg/kg together with the administration of CCl4 for inducing liver fibrosis. After 10 weeks, blood analysis, histopathology, oxidative stress, as well as protein and gene expression in the hepatic tissue were performed. Treatment with BA extract was able to reduce profibrotic markers by reducing the expression of α-SMA and Col-1 proteins, as well as reducing the formation of free radicals and lipid peroxidation. (BA extract showed anti-inflammatory effects in the liver by suppressing NF-kB activation and reducing gene expression of signaling targets (IL-6 and iNOS). The data obtained showed that BA extract has antifibrotic and anti-inflammatory effects.

Phase angle of bioimpedance as a marker of inflammation in cardiovascular diseases: A systematic review.

OBJECTIVE: The aim of this systematic review was to investigate whether phase angle (PhA) of bioelectrical impedance is associated with inflammatory markers in cardiovascular diseases (CVDs). METHODS: A search was performed in the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American Caribbean Health Sciences Literature (LILACS), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science and Scopus; and in the gray literature up to January 2022. Studies with individuals with CVDs were included, to evaluate the association between PhA and the inflammatory markers interleukin (IL)-6, IL-10, IL-18, IL-1ß, IL-33, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), toll-like receptor (TLR) 2, TLR 4, nuclear factor κB, pathogen-associated molecular pattern molecules, lipopolysaccharides, interferon-γ-inducing factor, and JAK STAT. RESULTS: We identified 755 articles and, after an eligibility analysis, 5 studies were included. The inflammatory markers investigated in the studies were CRP, TNF-α, and IL-33. In patients with CVDs, PhA was negatively associated with CRP and TNF-α in 80% and 100% of the studies, respectively. CONCLUSIONS: The present results suggested that PhA is inversely associated with inflammatory markers in individuals with CVDs, and its clinical use is encouraged for better therapeutic planning.

Coumaric acid from M. polymorphum extracts reverses the activated state of hepatic stellate cells (GRX) and inhibits their proliferation by decreasing the p53/p21 pathway.

Coumaric acid is a phenolic compound found in medicinal plants. Its use has been reported in the treatment of inflammatory diseases, prevention of alterations induced by oxidative stress, as well as acetaminophen-induced hepatotoxicity. Thus, this study evaluated coumaric acid as a potential treatment for liver fibrosis. Cell proliferation was assessed by the trypan blue exclusion technique and the cytotoxicity of coumaric acid was performed using an LDH assay. Mechanisms of cell apoptosis were evaluated by flow cytometry. The expression of genes associated with apoptosis, cell cycle control, and fibrosis was assessed by qPCR. The production of lipid droplets was quantified by oil red staining. The experiments performed showed that the treatment with coumaric acid was able to reduce cell proliferation without causing cell cytotoxicity or apoptosis. Coumaric acid was able to inhibit the expression of cyclin D1 and CDK's (CDK2, CDK4, and CDK6), increasing p53 and p21, which could lead to cell cycle arrest. Treatment with coumaric acid was also able to revert the activated phenotype of GRX cells to their quiescent state. Thus, our results suggest that coumaric acid has a potential therapeutic effect against liver fibrosis.

Moquiniastrum polymorphum subsp. polymorphum extract inhibits the proliferation of an activated hepatic stellate cell line (GRX) by regulating the p27 pathway to generate cell cycle arrest.

ETHNOPHARMACOLOGICAL RELEVANCE: The chosen plant and its extracts have been an alternative in the treatment of several inflammatory and oxidant diseases, and is therefore a viable option for the treatment of hepatic fibrosis. AIM OF THE STUDY: This study aimed to use Moquiniastrum polymorphum subsp. polymorphum, mainly the ethanolic extract and fractions, in the treatment of hepatic fibrosis. MATERIALS AND METHODS: Extracts were prepared from dried leaves in 100% ethanol (ET) and fractionated with an increased polarity solvent (dichloromethane to methanol). The quantification of compounds in the extracts was characterized by GCMS. The decrease in cell proliferation and the cytotoxicity of the extracts were evaluated together with the mechanisms of apoptosis and autophagy. The expression of genes associated with decreased fibrosis and cell cycle control was assessed and the production of lipid droplets was quantified by Oil Red O staining. RESULTS: The experiments showed that treatment with ET and fraction 1 (F1) inhibited the expression of CDKIs (CCDN1, CDK2, CDK4 and CDK6) through an increase in p27, related to an increase in autophagic vesicles. The extract and F1 were able to decrease proliferation and revert the activated state of GRX cells to their quiescent state. CONCLUSION: Our results suggest that extracts obtained from Moquiniastrum polymorphum subsp. polymorphum have a potential therapeutic effect against liver fibrosis.

Simvastatin attenuates inflammatory process on LPS-induced acute lung injury in mice.

Acute lung injury (ALI) is a disease of high prevalence and is characterized by the excessive production of inflammatory mediators in the lungs of people sick. Inflammation is the major characteristic of ALI and studies report that inhibition of inflammatory cytokines could be an alternative treatment. Statins such as Simvastatin (SV) are known to their use for cholesterol reduction but also for inflammatory and immunoregulatory processes. In this study, we evaluated the effects of SV on LPS-induced alveolar macrophages and in ALI mice model. Our study has demonstrated the protective effects of SV on LPS-activated alveolar macrophages RAW 264.7 and LPS-induced ALI in mice. SV treatment significantly inhibited the alveolar macrophages activation by decreasing the iNOS, IL-1ß, and IL-6 gene expression in vitro and in vivo. The treatment also decreased the inflammatory cells migration and the cytokines gene expression. Our findings suggest that SV can act as an anti-inflammatory agent for acute lung injury.

Bezafibrate reduces the damage, activation and mechanical properties of lung fibroblast cells induced by hydrogen peroxide.

In pulmonary fibrosis, the proliferation of fibroblasts and their differentiation into myofibroblasts is often caused by tissue damage, such as oxidative damage caused by reactive oxygen species, which leads to progressive rupture and thus destruction of the alveolar architecture, resulting in cell proliferation and tissue remodeling. Bezafibrate (BZF) is an important member of the peroxisome proliferator-activated receptor (PPARs) family agonists, used in clinical practice as antihyperlipidemic. However, the antifibrotic effects of BZF are still poorly studied. The objective of this study was to evaluate the effects of BZF on pulmonary oxidative damage in lung fibroblast cells. MRC-5 cells were treated with hydrogen peroxide (H2O2) to induce oxidative stress activation and BZF treatment was administered at the same moment as H2O2 induction. The outcomes evaluated were cell proliferation and cell viability; oxidative stress markers such as reactive oxygen species (ROS), catalase (CAT) levels and thiobarbituric acid reactive substances (TBARS); col-1 and α-SMA mRNA expression and cellular elasticity through Young's modulus analysis evaluated by atomic force microscopy (AFM). The H2O2-induced oxidative damage decreased the cell viability and increased ROS levels and decreased CAT activity in MRC-5 cells. The expression of α-SMA and the cell stiffness increased in response to H2O2 treatment. Treatment with BZF decreased the MRC-5 cell proliferation, ROS levels, reestablished CAT levels, decreased the mRNA expression of type I collagen protein (col-1) and α-smooth muscle actin (α-SMA), and cellular elasticity even with H2O2 induction. Our results suggest that BZF has a potential protective effect on H2O2-induced oxidative stress. These results are based on an in vitro experiment, derived from a fetal lung cell line and may emerge as a possible new therapy for the treatment of pulmonary fibrosis.