Sodium Butyrate Research Articles

English Effects of sodium butyrate and rosemary leaves on performance, biochemical parameters, immune status, and carcass traits of broiler chickens

English Effects of sodium butyrate and rosemary leaves on performance, biochemical parameters, immune status, and carcass traits of broiler chickens

Rolling-Translated circRUNX2.2 Promotes Lymphoma Cell Proliferation and Cycle Transition in Marek’s Disease Model

Marek’s disease (MD), an immunosuppressive disease induced by the Marek’s disease virus (MDV), is regarded as an ideal model for lymphoma research to elucidate oncogenic and anti-oncogene genes. Using this model, we found that circRUNX2.2, derived from exon 6 of RUNX2, was significantly upregulated in MDV-infected tumorous spleens. In this study, we deeply analyzed the potential role of circRUNX2.2 in lymphoma cells. An open reading frame (ORF) in circRUNX2.2 with no stop codon was predicted, and small peptides (named circRUNX2.2-rt) presenting multiple ladder-like bands with different molecular weights encoded by circRUNX2.2 were detected via Western blotting assay. The polysome fraction assay reconfirmed the translation ability of circRUNX2.2, which could be detected in polysome fractions. Subsequent analysis verified that it translated in a rolling circle manner, rather than being assisted by the internal ribosome entry site (IRES) or m6A-mediated mechanism. Furthermore, we found that circRUNX2.2-rt was potently induced in MSB1 cells treated with sodium butyrate (NaB), which reactivated MDV and forced the MDV transition from the latent to reactivation phase. During this phase, MDV particles were clearly observed by electron microscopy, and the viral gene pp38 was also significantly upregulated. A biological function study showed that circRUNX2.2-rt promoted cell proliferation and cell cycle transition from the S to G2 phase and inhibited the apoptosis of MSB1. Further immunoprecipitation and mass spectrometry assays showed that 168 proteins potentially interacting with circRUNX2.2-rt were involved in multiple pathways related to cell cycle regulation, which proved that circRUNX2.2-rt could bind or recruit proteins to mediate the cell cycle.

Expression of PGC-1α, PPAR-α and UCP1 genes, metabolic and anthropometric factors in response to sodium butyrate supplementation in patients with obesity: a triple-blind, randomized placebo-controlled clinical trial.

There is increasing evidence that gut metabolites have a role in the etiology of obesity. This study aimed to investigate the effects of sodium butyrate (NaB) supplementation on the expression of peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1α (PGC-1α), PPAR-α, and uncoupling protein-1 (UCP-1) genes, as well as on the metabolic parameters and anthropometric indices in persons with obesity. In this triple-blind placebo-controlled randomized clinical trial, 50 individuals with obesity were randomly assigned to NaB (600 mg/day) + hypo-caloric diet or placebo group + hypo-caloric diet for 8 weeks. The study measured the participants' anthropometric characteristics, food consumption, and feelings of hunger in addition to the serum levels of metabolic indices and the mRNA expression of the PGC-1α, PPAR-α, and UCP-1 genes in peripheral blood mononuclear cells (PBMCs). PGC-1α and UCP-1 genes expression significantly increased in NaB group compared to the placebo at the endpoint. A significant decrease in weight, BMI, and waist circumference (WC) was observed in NaB group. Among the metabolic factors, NaB significantly decreased fasting blood sugar (FBS) (P = 0.04), low-density lipoprotein cholesterol (LDL-C) (P = 0.038) and increased high-density lipoprotein cholesterol (HDL-C) (P = 0.016). NaB could not significantly change serum GLP-1 level. This study unveiled NaB supplementation alone cannot have significant beneficial effects on anthropometric, and biochemical factors. NaB could affect anthropometric and metabolic risk variables associated with obesity only when prescribed, along with calorie restriction. This study was registered in the Iranian Registry of Clinical Trials ( https://en.irct.ir/trial/53968 ) on 31 January 2021 (registry number IRCT20190303042905N2).

Sodium Butyrate as Gut Microbiota Modulators: Mechanisms of Action and Potential Clinical Applications - Literature Review and New Perspectives

IntroductionSodium butyrate is an organic chemical compound belonging to sodium salts, which has the potential to be used in anticancer therapy. It reduces inflammation of the intestinal mucosa and promotes the development of beneficial intestinal flora, thanks to which it helps maintain homeostasis. Therefore, butyrate reduces the risk of developing colon cancer or reverses pathological changes occurring under the influence of this cancer. Scientific studies have also shown a beneficial effect of butyrate on the side effects of anticancer treatment - chemotherapy and radiotherapy. A proper diet also has a beneficial effect on the production of endogenous butyrate and reduces the risk of developing colon cancer. It is recommended to use a Mediterranean diet, rich in dietary fiber, highly unsaturated fatty acids and fresh vegetables and fruits. It is recommended to avoid highly processed products, rich in simple sugars and saturated fatty acids, and to limit the consumption of red meat. Materials and methods This article is based on the literature found in the PubMed and other scientific databases from the period of 1978-2023 with the use of key words such as “butyrate” “sodium butyrate” “colon cancer” “anticancer treatment” “intestinal microbiota” “Mediterranean diet” Conclusion Sodium butyrate is a potential substance that, through its properties, may support the treatment of colorectal cancer. Additionally, the use of an appropriate diet has a positive effect on the intestinal microflora, allowing the action of sodium butyrate and reducing the risk of colorectal cancer.

Probiotic and sodium butyrate in dog food: effects on digestibility and hematological, metabolic and oxidative biomarkers

Probiotic and sodium butyrate in dog food: effects on digestibility and hematological, metabolic and oxidative biomarkers

Sodium butyrate activates peroxisome proliferator-activated receptor γ to suppress lithogenic diet-induced cholesterol gallstones in mice

Sodium butyrate activates peroxisome proliferator-activated receptor γ to suppress lithogenic diet-induced cholesterol gallstones in mice

Review of the effects of sodium butyrate on obesity, inflammatory bowel disease, pregnancy and colorectal cancer

Introduction and Purpose: Short-chain fatty acids (SCFAs), including butyric acid, acetic acid and propionic acid, are naturally produced in the large intestine by bacterial fermentation of insoluble carbohydrates and oligosaccharides. Butyric acid, which is the main source of energy for colon cells, has regenerative, cytoprotective and anti-inflammatory effects. Its physiological importance lies in maintaining the integrity and function of the intestinal epithelium, which protects the body against pathogens and oxidative stress. SCFA deficiencies resulting from low dietary fiber supply can lead to intestinal disorders. Supplementation with sodium butyrate, particularly using micro-encapsulation technology, enables efficient delivery of butyric acid to the gut, which may be beneficial in the treatment of inflammatory bowel disease and in the prevention of obesity and insulin resistance. Sodium butyrate (NaB) also has promising potential in the treatment of colorectal cancer (CRC), inducing apoptosis of cancer cells, increasing sensitivity to radiotherapy and chemotherapy and protecting healthy cells. SCFAs, especially butyrate, play a key role in reproductive medicine, oncology and gastroenterology, contributing to the maintenance of health and being potential therapeutic targets. The aim of this paper is to review the available literature on this topic. Material and methods: The review was based on articles obtained from PubMed scientific database published from 2014-2024, using the following keywords: sodium butyrate, obesity, pregnancy, inflammatory bowel disease, colorectal cancer, SCFA. Conclusions: Studies confirm the beneficial effects of sodium butyrate on metabolism, intestinal integrity and reduction of inflammation, opening up new possibilities in the treatment of metabolic disorders and intestinal diseases. However, further clinical studies conducted on humans are still needed, as most of the work to date has been conducted on mice and/or rats.

Sodium butyrate alleviates T-2 toxin-induced liver toxicity and renal toxicity in quails by modulating oxidative stress-related Nrf2 signaling pathway, inflammation, and CYP450 enzyme system.

T-2 toxin is a member of class A aspergilloides toxins, one of the most prevalent mycotoxins that contaminate feed and food. Direct ingestion of animals or feed contaminated by T-2 toxin can cause various animal diseases. Butyrate is an organic fatty acid featuring a four-carbon chain, which is commonly found in the form of sodium butyrate (NaB). NaB has several biological functions and pharmacological effects. However, the role of sodium butyrate in alleviating T-2 toxin-induced hepatorenal toxicity has not been explored. In this study, 240 juvenile quails were evenly assigned into 4 groups. The experimental setup comprised four groups: The control group received a standard diet; the toxin group received a diet containing 0.9mg/kg T-2 toxin; the butyrate group received a diet containing 0.5g/kg NaB; and the T-2 treatment group received a diet containing both 0.9mg/kg T-2 toxin and 0.5g/kg NaB. We evaluated the histopathological changes in the kidney and liver on Days 14 and 28 and explored the molecular mechanisms involving oxidative stress, inflammation, and expression of nuclear xenobiotic receptors (NXRs). Our results showed that T-2 toxin exposure-induced inflammation in the liver and kidney by activating the oxidative stress pathway and modulating expression of NXRs to regulate related CYP450 isoforms, ultimately leading to histopathological injury in the liver and kidney, whereas sodium butyrate ameliorated this injury. These results offer novel insights into the molecular mechanisms underlying the protective effects of sodium butyrate in mitigating T-2 toxin-induced hepatorenal injury in juvenile quails. PRACTICAL APPLICATION: The mechanisms of T-2 toxin toxicity have been well described in experimental animals, but studies in birds are limited. With the development of society, the market scale of quails farming has been expanding, and the value of quails meat and eggs is increasing; there is an urgent need to clarify the harm of T-2 toxin to quails and its mechanism.

Effects of Oral Butyrate on Blood Pressure in Patients With Hypertension: A Randomized, Placebo-Controlled Trial.

The microbiota-derived short chain fatty acid butyrate has been shown to lower blood pressure (BP) in rodent studies. Nonetheless, the net effect of butyrate on hypertension in humans remains uncovered. In this study, for the first time, we aimed to determine the effect of oral butyrate on BP in patients with hypertension. We performed a double-blind randomized placebo-controlled trial including 23 patients with hypertension. Antihypertensive medication was discontinued for the duration of the study with a washout period of 4 weeks before starting the intervention. Participants received daily oral capsules containing either sodium butyrate or placebo with an equivalent dosage of sodium chloride for 4 weeks. The primary outcome was daytime 24-hour systolic BP. Differences between groups over time were assessed using linear mixed models (group-by-time interaction). Study participants (59.0±3.7 years; 56.5% female) had an average baseline office systolic BP of 143.5±14.6 mm Hg and diastolic BP of 93.0±8.3 mm Hg. Daytime 24-hour systolic and diastolic BP significantly increased over the intervention period in the butyrate compared with the placebo group, with an increase of +9.63 (95% CI, 2.02-17.20) mm Hg in daytime 24-hour systolic BP and +5.08 (95% CI, 1.34-8.78) mm Hg in diastolic BP over 4 weeks. Butyrate levels significantly increased in plasma, but not in feces, upon butyrate intake, underscoring its absorption. Four-week treatment with oral butyrate increased daytime systolic and diastolic BP in subjects with hypertension. Our findings implicate that butyrate does not have beneficial effects on human hypertension, which warrants caution in future butyrate intervention studies. URL: https://onderzoekmetmensen.nl/; Unique identifier: NL8924.

Sodium Butyrate Ameliorates Postoperative Delirium by Regulating Gut Microbiota Dysbiosis to Inhibit Astrocyte Activation in Aged Mice.

Postoperative delirium (POD) is a common complication in elderly surgical patients, with limited targeted interventions due to incomplete understanding of its pathophysiological mechanisms. Central nervous system (CNS) inflammation, involving glial cell activation, particularly astrocytes, is considered crucial in POD development. Butyrate, a four-carbon fatty acid, has shown protective effects in CNS diseases, but its potential in mitigating POD remains unclear. This study aimed to investigate the impact of sodium butyrate on POD in aged mice. Behavioral tests, including open field, Y maze, and food burying tests, demonstrated that sodium butyrate preconditioning ameliorated laparotomy-induced delirium in aged mice. Pre-treatment with sodium butyrate inhibited astrocyte activation in the hippocampus, reduced interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expression levels, and protected hippocampal neurons. Furthermore, the study revealed a connection between gut microbiota regulation and central neuroprotective effects mediated by astrocyte activation inhibition. Sodium butyrate improved the intestinal morphological barrier by rebalancing gut microbiota, inhibiting Proteobacteria and Actinobacteria, reducing Allobaculum and Bacteroides abundance, and increasing Oscillospira abundance. This regulation decreased gut permeability, limiting the entry of toxic substances into the bloodstream, thereby reducing inflammation spread and astrocyte overactivation, leading to central anti-inflammatory effects. In conclusion, sodium butyrate may ameliorate POD by inhibiting astrocyte-mediated neuroinflammation through gut microbiota rebalancing.

The hepatoprotective effect of sodium butyrate on hepatic inflammatory injury mediated by the NLRP3 inflammatory pathway in subchronic fluoride-exposed mice.

Excessive subchronic fluoride exposure can cause severe damage to detoxification organs, including the liver. Sodium butyrate has anti-inflammatory, antitumor, antioxidant and immunomodulatory properties. However, relatively few studies have investigated the effects of sodium butyrate on liver injury caused by subchronic fluoride exposure. The purpose of this research was to investigate the effect and mechanism of sodium butyrate on fluoride-induced hepatic inflammatory injury via the expression of nod-like receptor protein 3 (NLRP3). Mice were subjected to randomization into four groups, control group (C), fluorosis group (F), sodium butyrate alone group (S), and treatment group (Y). The mice in groups F and F + S drank 100mg/L sodium fluoride-containing distilled water freely every day. After fluoride exposure lasted for 3 months, the mice in group S and F + S were gavaged with sodium butyrate daily at a concentration of 1000mg/kg. Following the treatment regimen, liver specimens were collected for analysis. The mRNA and protein expression levels of inflammatory factors and NLRP3 and its downstream gene were measured by RT-qPCR and western blotting. The histological hematoxylin and eosin (H&E) staining of liver showed that the subchronic fluoride-exposed group were chronic inflammation. The liver of treatment group were less vacuolar degeneration and inflammatory infiltration. The results of the biochemical assay showed that the subchronic fluoride-exposed group were liver injury. In addition, the detection of oxidative stress indicators showed that chronic subchronic fluoride exposure could lead to an increase in the level of oxidative stress in the liver, and the treatment alleviated this increase. RT-qPCR results showed that compared with those in the control group, the mRNA levels of the inflammatory factors TNF-α, IL-6 and IL-1β, the NLRP3 inflammasome and its downstream factors NLRP3, caspase-1, gasdermin D (GSDMD) and IL-18 increased in the liver tissue of mice in the subchronic fluoride-exposed group. Sodium butyrate released inflammatory factors during subchronic fluoride exposure and inhibited the protein expression of activated NLRP3 to a certain extent. Sodium butyrate may play a protective role by antagonizing the production of activated inflammasomes and their downstream inflammatory factors in the livers of subchronic fluoride-exposed mice.

Next-Generation Sequencing to Determine Changes in the Intestinal Microbiome of Juvenile Sturgeon Hybrid (Acipenser gueldenstaedtii♀ × Acipenser baerii♂) Resulting from Sodium Butyrate, Β-Glucan and Vitamin Supplementation

Background/Objectives: The effect of sodium butyrate (NaB), β-glucan (βG) and vitamins in the diet on gut microbiome, cortisol level, lysozyme activity and growth parameters of juvenile hybrid sturgeon (Acipenser gueldenstaedtii♀ × Acipenser baerii♂) was determined. Methods: Sturgeon hybrids (n = 144) were divided into three groups with enriched feeding (mg/kg of feed): FQV1 (50 NaB; 20 βG; const. vitamins), FQV2 (150 NaB; 20 βG; const. vitamins), FQV3 (50 NaB; 60 βG; const. vitamins) and control (not supplemented), each group in triplicate, 12 fish in each repetition. Rearing was carried out for 30 days in controlled conditions. Gut microbiome was characterized using Next Generation Sequencing (NGS) of DNA samples isolated from intestinal content. Cortisol level was determined using the ELISA test. Lysozyme activity was measured by turbidimetric test. Results: Based on data obtained from NGS, it was determined that the FQV1 group is characterized by the highest values of diversity indices (Shannon, Simpson and Chao-1) and the largest number of ASVs (Amplicon Sequence Variants). The highest abundance of probiotic bacteria (Lactobacillus, Lactococcus) was determined in the FQV1 group. The highest cortisol concentration was determined in the control (33.26 ng/mL), while the lowest was in FQV3 (27.75 ng/mL). The highest lysozyme activity was observed in FQV1 (154.64 U/mL), and the lowest in FQV2 (104.39 U/mL) and control (121.37 U/mL) (p < 0.05). FQV2 was characterized by significantly more favorable values of breeding indicators (p < 0.05). Conclusions: The obtained results prove that an appropriate composition of NaB, βG and vitamins can be used in the commercial breeding of juvenile hybrid sturgeons.

Analyzing the morphology and avian β-defensins genes (AvβD) expression in the small intestine of Cobb500 broiler chicks fed with sodium butyrate

BackgroundSodium butyrate is a potential antibiotic growth promoter and has had advantageous effects on the poultry industry.MethodsEvaluating the effect of sodium butyrate on the intestinal villi and the humoral part of innate immunity of the male Cobb 500 broiler using scanning electron microscopy and quantitative real-time PCR analysis, the control group and treated group of Cobb 500 with SB supplemented received water containing 0.98 mg sodium butyrate.ResultsThe administration of sodium butyrate changed the villi characters, as the shape changed from tongue to long tongue. They were mainly parallel to each other and long finger-like at the duodenum. The tips of the villi in the control group appeared thin-slight curved with a prominent center in the duodenum, thin rectangular in the jejunum, and ileum in the control group. In contrast, in the treatment group, they changed to thick rectangular in the duodenum and ileum zigzag shape in the jejunum. The epithelium lining of the duodenal villi showed a dome shape, the jejunal villi showed a polygonal shape, and the ileal villi appeared scales-like. The epithelium lining showed irregular microfolds and many different-sized pores, and the treatment group showed islands of long microvilli in the duodenum and solitary long microvilli in the ileum. Real-time PCR of AvBD 1, 2, 10, and 12 significantly (P < 0.01). The better expression of AvBD 1, 2, and 12 was determined in the duodenum, while AvBD 10 was in the jejunum.ConclusionSodium butyrate enhanced the chicks’ growth and small intestine parameters, modified the morphology of the intestinal villi, and improved the humoral part of innate immunity.

Exploring the Therapeutic Potential of Sodium Butyrate in Irritable Bowel Syndrome. A Literature Review

Introduction and purpose Irritable bowel syndrome (IBS) is a prevalent digestive condition marked by symptoms like abdominal discomfort, bloating, and irregular bowel movements. Sodium butyrate, a short-chain fatty acid recognized for its anti-inflammatory effects and benefits to gut health, has gained attention as a potential treatment for IBS. This review seeks to assess the existing research on the effectiveness and safety of sodium butyrate in managing IBS. Material and methods This work was based on a review of the literature available on PubMed. We included studies corresponding to the keywords: sodium butyrate, irritable bowel disease, butyric acid. Results Research has shown that sodium butyrate supplementation significantly alleviated abdominal pain, bloating, and overall IBS symptoms compared to a placebo. Notable improvements were seen in both visceral pain sensitivity and gut permeability. Furthermore, combining sodium butyrate with probiotics may offer additional benefits. The treatment was generally well-tolerated, easily accessible, and cost-effective. Conclusion Sodium butyrate shows promise as a therapeutic option for managing IBS, with studies indicating its effectiveness in reducing symptoms and enhancing gut health. However, more extensive, well-structured clinical trials are required to validate these results, determine optimal dosage, and assess long-term safety and efficacy.

Effect of Dietary Short-Chain Fatty Acids on the Immune Status and Disease Resistance of European Seabass Juveniles

(1) Background: This study aimed to evaluate the potential of short-chain fatty acids as functional ingredients to improve the immune status and disease resistance of European seabass (Dicentrarchus labrax) juveniles. (2) Methods: For that purpose, triplicate groups of fish with an initial body weight of 15.2 ± 0.03 g were fed isoproteic (43% crude protein) and isolipidic (18% crude lipids) diets supplemented with sodium acetate (SA), sodium propionate (SP), and sodium butyrate (SB) at two inclusion levels: 0.25% and 0.50%. An unsupplemented diet was used as a control. After 56 days of feeding with the experimental diets, fish were intraperitoneally (i.p.) injected with 100 µL of Vibrio anguillarum (1.2 × 107 Colony Forming Units (CFU)/mL) and mortality was recorded for 3 weeks. At the end of the trial, there were no differences in survival between the treatment groups and the control, but survival was higher in fish fed the diet supplemented with SB 0.50 than SP 0.25 (93.3 vs. 66.7%). Compared to the pre-challenge values, and regardless of diet composition, all hematological parameters (hemoglobin, hematocrit, red blood cells, white blood cells) measured decreased after 4 h of bacterial challenge, except for neutrophils which were increased. Independently of diet composition, lysozyme and nitric oxide decreased at 4 and 24 h post infection. Compared to the control, diets supplemented with SA and SP promoted an up-regulation of both pro- and anti-inflammatory cytokines at 4 h after the challenge, while the diets supplemented with SB promoted an up-regulation of pro- and anti-inflammatory cytokines at 24 h after the challenge. (3) Conclusions: Overall, present results suggest that SA and SP provide a fast response to a bacterial challenge in European sea bass juveniles, while SB provides increased survival.

Assessment of Sodium Butyrate’s Pharmacological Effects on Gentamicin-induced Nephrotic Disorders in a Rat Model

Background Sodium butyrate (SB) used to increase oxidative stress was reduced and the glutathione redox pathway was boosted. It inhibits proliferation, induction of differentiation, and induction or repression of gene expression and it has also anti-inflammatory action. This is endorsed for suppression of nephrotic symptoms. Objectives The present study was carried out to evaluate the nephroprotective activity of SB on gentamicin-induced nephrotoxicity in rats. Materials and Methods Present research work was designed to estimate pharmacological potential of SB in gentamicin-induced nephrotic disorder. The pharmacological prospective was estimated in gentamicin-induced rats through the oral administration of SB formulation 200 mg/kg and 300 mg/kg BW. Results The study observed that the SB significantly protects the kidneys from gentamicin-induced nephrotic disorders. Gentamicin 100 mg/kg for 7 days was used for induction of nephrotoxicity in Wistar rats by intraperitoneal administration. The administration of SB was observed to decrease the occurrence of glomerular congestion, vascular congestion, epithelial desquamation, inflammatory cell build-up, and kidney cell necrosis induced by gentamicin. The dose of SB maintained the gentamicin-induced increased creatinine (0.62±0.05), serum urea (18.10±0.79), uric acid (2.10±0.28), and blood urea nitrogen (BUN) (17.56±0.55) levels. This fact is further sustained by the histopathological examinations. Conclusion Sodium butyrate formulation with antinephrotic activity in maintaining uremic solutes such as urea, uric acid, creatinine, BUN, ketone, urobilinogen, glucose, specific gravity, and urine pH in Wistar rats with gentamicin-induced glomerulonephritis (GN). The SB was administered to the animals at doses of 200 and 300 mg/kg body weight. Pretreatment with the drug showed promising results in maintaining elevated parameters in nephritic rats within a short duration.

Sodium butyrate protect bone mass in lipopolysaccharide-treated rats by reducing oxidative stress and inflammatory

ABSTRACT Objective The study will be to observe the effect of Sodium butyrate (NaB) on bone loss in lipopolysaccharide (LPS)-treated rats. Methods In the rat model, we observed that changes in the expression of oxidative stress regulators, inflammatory markers and target genes were measured by immunofluorescence and RT–PCR after treatment. Changes in viability and osteogenesis of MC3T3-E1, osteoclast differentiation in RAW264.7 cells in the presence of LPS were evaluated using CCK-8, ALP staining, RES staining, and TRAP staining. Results In vitro experiments have shown that LPS-induced inhibition of JC-1, SIRT1, GPX1 and SOD2 is associated with increased levels of inflammation and oxidative stress. In addition, NaB has been found to suppress oxidative stress, inflammation and Mito SOX, promote osteogenic differentiation, and inhibit osteoclast differentiation. In addition, NaB significantly promoted SITR1 expression, repaired impaired bone metabolism, and improved bone strength and bone mineral density. Conclusion Given all this experimental evidence, the results strongly suggest that NaB can restore osteogenic activity in the presence of LPS by reducing intracellular ROS, inhibiting osteoclast differentiation and reducing bone loss in LPS-treated rat models.

Sodium butyrate alleviates lipopolysaccharide-induced inflammation through JAK/STAT signalling in primary human corneal fibroblasts

BackgroundBacterial keratitis is a common cause of blindness. Antibiotic treatment leads to the rapid release of lipopolysaccharide (LPS), which can activate corneal fibroblasts and cause persistent and excessive inflammatory responses. The anti-inflammatory drugs currently used to treat keratitis have serious side effects. Therefore, the ability of sodium butyrate (NaB), which can suppress the production of proinflammatory cytokines and promote the production of anti-inflammatory cytokines, to ameliorate keratitis was assessed in the present study. MethodsThe effect of NaB on the viability of primary human corneal fibroblasts was assayed with a CCK-8 kit. Cell migration was assessed by an in vitro scratch assay. Cell phenotypes were assessed by Western blotting and immunofluorescence staining. An antibody array was used to measure the production of proinflammatory cytokines and chemokines. ResultsAt 0–1 mM, NaB had no significant effect on cell viability, promoted the expression of the keratocyte marker keratocan and inhibited the fibroblast marker vimentin. Inhibition of cell migration was observed in the wound healing assay. By targeting the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway, NaB decreased the levels of inflammation-related cytokines and chemokines whose expression was induced by LPS. ConclusionsNaB maintained the keratocyte phenotype, inhibited cell migration, and relieved LPS-induced inflammatory responses through the JAK/STAT signalling pathway.

Fluoride Alters Gene Expression via Histone H3K27 Acetylation in Ameloblast-like LS8 Cells.

Excessive fluoride ingestion during tooth development can cause dental fluorosis. Previously, we reported that fluoride activates histone acetyltransferase (HAT) to acetylate p53, promoting fluoride toxicity in mouse ameloblast-like LS8 cells. However, the roles of HAT and histone acetylation status in fluoride-mediated gene expression remain unidentified. Here, we demonstrate that fluoride-mediated histone modification causes gene expression alterations in LS8 cells. LS8 cells were treated with or without fluoride followed by ChIP-Seq analysis of H3K27ac. Genes were identified by differential H3K27ac peaks within ±1 kb from transcription start sites. The levels of mRNA of identified genes were assessed using rea-time PCR (qPCR). Fluoride increased H3K27ac peaks associated with Bax, p21, and Mdm2 genes and upregulated their mRNA levels. Fluoride decreased H3K27ac peaks and p53, Bad, and Bcl2 had suppressed transcription. HAT inhibitors (Anacardic acid or MG149) suppressed fluoride-induced mRNA of p21 and Mdm2, while fluoride and the histone deacetylase (HDAC) inhibitor sodium butyrate increased Bad and Bcl2 expression above that of fluoride treatment alone. To our knowledge, this is the first study that demonstrates epigenetic regulation via fluoride treatment via H3 acetylation. Further investigation is required to elucidate epigenetic mechanisms of fluoride toxicity in enamel development.

Sodium butyrate improves cognitive dysfunction in high-fat diet/ streptozotocin-induced type 2 diabetic mice by ameliorating hippocampal mitochondrial damage through regulating AMPK/PGC-1α pathway

Cognitive dysfunction is an important comorbidity of type 2 diabetes mellitus (T2DM). Sodium butyrate (NaB) is a short-chain fatty acid and has an effect improving T2DM-associated cognitive dysfunction. Using a high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mouse model, the present study investigated the mechanism involved in the beneficial effect of butyrate on diabetic cognitive dysfunction, with a focus on ameliorating mitochondrial damage through regulating the adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α (AMPK/PGC-1α) pathway considering the important role of mitochondrial impairments in the occurrence of T2DM-associated cognitive dysfunction. We found, based on reconfirmation of the improvement of NaB on cognitive impairment, that NaB treatment improved damaged synaptic structural plasticity including the decrease in dendritic spine density and downregulation in the expression of postsynaptic density protein 95 and synaptophysin in the hippocampus in the model mice. NaB treatment also ameliorated mitochondrial ultrastructural damage, increased mitochondrial membrane potential and adenosine 5′-triphosphate content, and improved mitochondrial biogenesis and dynamics in the model mice. Furthermore, the expression of phosphorylated AMPK and PGC-1α was upregulated after NaB treatment in the model mice. In particular, the above beneficial effects of NaB were blocked by the inhibition of either AMPK or PGC-1α. In conclusion, NaB treatment improved cognitive impairment and damaged synaptic structural plasticity in the hippocampus by ameliorating damage to mitochondrial morphology and function through regulating the AMPK/PGC-1α pathway in HFD/STZ-induced T2DM mice.