Abstract  Introduction: Short chain fatty acids (SCFA) acetate, propionate and butyrate are the major anions produced by the bacterial fermentation of dietary fiber (DF) in colon. Recently, butyrate has been recently studied because is important to maintain colonic functions and because it has been related with a protective effect in colorectal cancer, which is mainly, explained by its potential to regulate gene expression by inhibiting enzyme histone-deacetylase (HDAC). Several investigationsshown that SCFAreceptor GPR43 is involved insignal transduction mechanisms once they bind to ligands such as butyrate to generate different physiological effects in colonocytes. Objective: Determine if dietary fiber consumption from nopal (Opuntia ficus I.) containing a ratio of soluble-insoluble fiber 40/60, has a direct influence on the quantitative expression of butyrate-specific receptor GPR43. Methods: Wistar rats were fed with four different diets formulated at different concentrations of dietary fiber of 0, 5, 15 and 25% of dietary fiber from opuntia, respectively. Results and discussion: The results shown an increase in the expression of GPR43 (93.1%) when rats was fed with a 5% fiber diet, using beta-actin as a reference gene. The results of this investigation will contribute to determinate the relation of diet with intestinal health for the purpose of expanding the knowledge of butyric acid on colonic functions. (Nutr Hosp. 2011;26:1052-1058) DOI: 10.3305/nh.2011.26.5.5054

Abstract  BACKGROUND: In ulcerative colitis (UC) butyrate metabolism is impaired due to a defect in the butyrate oxidation pathway and/or transport. In the present study we correlated butyrate uptake and oxidation to the gene expression of the butyrate transporter SLC16A1 and the enzymes involved in butyrate oxidation (ACSM3, ACADS, ECHS1, HSD17B10, and ACAT2) in UC and controls.

METHODS: Colonic mucosal biopsies were collected during endoscopy of 88 UC patients and 20 controls with normal colonoscopy. Butyrate uptake and oxidation was measured by incubating biopsies with (14) C-labeled Na-butyrate. To assess gene expression, total RNA from biopsies was used for quantitative reverse-transcription polymerase chain reaction (qRT-PCR). In 20 UC patients, gene expression was reassessed after treatment with infliximab.

RESULTS: Butyrate uptake and oxidation were significantly decreased in UC versus controls (P < 0.001 for both). Butyrate oxidation remained significantly reduced in UC after correction for butyrate uptake (P < 0.001), suggesting that the butyrate oxidation pathway itself is also affected. Also, the mucosal gene expression of SLC16A1, ACSM3, ACADS, ECHS1, HSD17B10, and ACAT2 was significantly decreased in UC as compared with controls (P < 0.001 for all). In a subgroup of patients (n = 20), the gene expression was reassessed after infliximab therapy. In responders to therapy, a significant increase in gene expression was observed. Nevertheless, only ACSM3 mRNA levels returned to control values after therapy in the responders groups.

CONCLUSIONS: The deficiency in the colonic butyrate metabolism in UC is initiated at the gene expression level and is the result of a decreased expression of SLC16A1 and enzymes in the β-oxidation pathway of butyrate.

Abstract  The objective of this study was the evaluation of the inclusion of calcium propionate, sodium butyrate and sodium monensin in the starter concentrate on ruminal parameters and forestomach development in dairy calves. Fifteen newborn Holstein calves were rumen cannulated and housed in individual stalls until ten weeks old, with free access to water, fed 4 liters of milk per day. split in two meals, and starter concentrate ad libitum containing sodium butyrate (0.15%), sodium monensin (30 m) or calcium propionate (0.15%). Starting at the fourth week of life, before and 2 hours after the morning feeding, ruminal fluid samples were taken weekly to determine the pH, short-chain fatty acids and ammonia-N. After 10 weeks, the animals were slaughtered to assess the forestomach growth. The rumen pH was affected by sampling time and the additives used in the starter concentrate. The total short-chain fatty acids concentration and each fatty acid concentration, were was not affected by the additives. However, except for molar concentration of acetic acid, all rumen fermentation parameters were affected by sampling time. The total forestomach weight and the average weight of each compartment and the maximum reticulum-rumen capacity were not affected by additives Supplied in the starter concentrate. No significant effects of the additives were observed on the height, width and number of papillae of the ruminal epithelium. The inclusion of these additives in starter concentrate had no effect on most of the ruminal parameters and forestomach development in suckling calves.

Abstract  In milk-fed calves, the effects of sodium-butyrate (Na-butyrate) to replace flavomycin on growth performance and some mechanisms involved were studied. Pancreatic and intestinal morphology, digestive enzyme activities, plasma gut regulatory peptide concentrations, and expression of their receptors in the gastrointestinal tract were measured. Gastrointestinal tract defense systems were examined by measuring protein levels of 2 heat-shock proteins (HSP27 and HSP70). The calves were randomly allocated into 2 groups fed the same basic diet with flavomycin as an antimicrobial growth promoter or with Na-butyrate (3 g/kg of dry matter). Sodium-butyrate disappeared quickly in the upper gut and was not found in circulating blood. Supplementation with Na-butyrate enhanced growth rate and improved feed conversion into body weight gain compared with the flavomycin group. Supplementation with Na-butyrate was likely associated with an improvement in efficacy of the gastrointestinal tract digestive capacities expressed by enhanced production of digestive enzymes and increased absorptive capacities in the upper small intestine. The effects could have been controlled by insulin-like growth factor-1 but probably not by any of the cholecystokinin/gastrin peptide family. Concentrations of HSP27 and HSP70 were increased in stomach and colon of calves receiving Na-butyrate, thereby assuring protection of cells with intensive metabolism (chaperone function). In conclusion, beneficial effects of Na-butyrate on maturation of gastrointestinal functions were shown in milk-fed calves and may be applied to young mammals of other species.

Abstract  While conservation of ATP is often a desirable trait for microbial production of chemicals, we demonstrate that additional consumption of ATP may be beneficial to drive product formation in a nonnatural pathway. Although production of 1-butanol by the fermentative coenzyme A (CoA)-dependent pathway using the reversal of β-oxidation exists in nature and has been demonstrated in various organisms, the first step of the pathway, condensation of two molecules of acetyl-CoA to acetoacetyl-CoA, is thermodynamically unfavorable. Here, we show that artificially engineered ATP consumption through a pathway modification can drive this reaction forward and enables for the first time the direct photosynthetic production of 1-butanol from cyanobacteria Synechococcus elongatus PCC 7942. We further demonstrated that substitution of bifunctional aldehyde/alcohol dehydrogenase (AdhE2) with separate butyraldehyde dehydrogenase (Bldh) and NADPH-dependent alcohol dehydrogenase (YqhD) increased 1-butanol production by 4-fold. These results demonstrated the importance of ATP and cofactor driving forces as a design principle to alter metabolic flux.

Abstract  An Escherichia coli strain was engineered to synthesize 1-hexanol from glucose by extending the coenzyme A (CoA)-dependent 1-butanol synthesis reaction sequence catalyzed by exogenous enzymes. The C4-acyl-CoA intermediates were first synthesized via acetyl-CoA acetyltransferase (AtoB), 3-hydroxybutyryl-CoA dehydrogenase (Hbd), crotonase (Crt), and trans-enoyl-CoA reductase (Ter) from various organisms. The butyryl-CoA synthesized was further extended to hexanoyl-CoA via β-ketothiolase (BktB), Hbd, Crt, and Ter. Finally, hexanoyl-CoA was reduced to yield 1-hexanol by aldehyde/alcohol dehydrogenase (AdhE2). Enzyme activities for the C6 intermediates were confirmed by assays using HPLC and GC. 1-Hexanol was secreted to the fermentation medium under anaerobic conditions. Furthermore, co-expressing formate dehydrogenase (Fdh) from Candida boidinii increased the 1-hexanol titer. This demonstration of 1-hexanol production by extending the 1-butanol pathway provides the possibility to produce other medium chain length alcohols using the same strategy.

Abstract  Sodium butyrate (NaBu) is known to exhibit anti-cancer effects via the differentiation and apoptosis of various carcinoma cells. However, the mechanism by which NaBu induces apoptosis and the involvement of protein kinases during apoptosis is not completely understood. To investigate the underlying pathways, we performed cell culture experiments in androgen-independent human prostate cancer (DU145 cells) focusing on various protein kinases. NaBu causes concentration-dependent cell detachment and growth inhibition. Exposure of DU145 cells to NaBu for 24 h caused a strong apoptotic effect with 26% nuclear fragmentation and condensation. In addition, NaBu induced caspase-3 and poly-ADP ribose polymerase cleavage and up-regulation of bax, suggesting that mitochondrial damage is involved in NaBu-induced caspase-dependent apoptosis. Interestingly, NaBu stimulated p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) activation, but not extracellular signal-regulated kinase 1/2 activation during apoptosis. Furthermore, NaBu up-regulated total protein levels and phospho forms of MAPK kinase 3 (MKK3) and MAPK kinase 4 (MKK4) as the upstream kinases of p38 MAPK and JNK independently of oxidative stress. Taken together, it is suggested that NaBu can be a promising chemopreventive agent for prostate cancer and the p38 MAPK and JNK pathways have critical roles in NaBu-induced apoptosis in DU145 cells.

Abstract  Butyric acid (butanoic acid) belongs to a group of short-chain fatty acids and is thought to play several beneficial roles in the gastrointestinal tract. Butyric anion is easily absorbed by enteric cells and used as a main source of energy. Moreover, butyric acid is an important regulator of colonocyte proliferation and apoptosis, gastrointestinal tract motility and bacterial microflora composition in addition to its involvement in many other processes including immunoregulation and anti-inflammatory activity. The pathogenesis of irritable bowel syndrome (IBS), the most commonly diagnosed functional gastrointestinal condition, is complex, and its precise mechanisms are still unclear. This article describes the potential benefits of butyric acid in IBS.

Abstract  Soluble dietary fibers promote metabolic benefits on body weight and glucose control, but underlying mechanisms are poorly understood. Recent evidence indicates that intestinal gluconeogenesis (IGN) has beneficial effects on glucose and energy homeostasis. Here, we show that the short-chain fatty acids (SCFAs) propionate and butyrate, which are generated by fermentation of soluble fiber by the gut microbiota, activate IGN via complementary mechanisms. Butyrate activates IGN gene expression through a cAMP-dependent mechanism, while propionate, itself a substrate of IGN, activates IGN gene expression via a gut-brain neural circuit involving the fatty acid receptor FFAR3. The metabolic benefits on body weight and glucose control induced by SCFAs or dietary fiber in normal mice are absent in mice deficient for IGN, despite similar modifications in gut microbiota composition. Thus, the regulation of IGN is necessary for the metabolic benefits associated with SCFAs and soluble fiber.

Abstract  AIM: Paracrine interaction between macrophages and adipocytes in obese visceral fat tissues is thought to be a trigger of chronic inflammation. The immunomodulatory effect of the short chain fatty acid, butyric acid, has been demonstrated. We hypothesize that sodium butyrate (butyrate) attenuates inflammatory responses and lipolysis generated by the interaction of macrophages and adipocytes.

METHODS: Using contact or transwell co-culture methods with differentiated 3T3-L1 adipocytes and RAW264.7 macrophages, we investigated the effects of butyrate on the production of tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), and the release of free glycerol, free fatty acids (FFAs) into the medium. We also examined the activity of nuclear factor-kappaB (NF-κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs) in co-cultured macrophages, as well as lipase activity and expression in co-cultured adipocytes.

RESULTS: We found increased production of TNF-α, MCP-1, IL-6, and free glycerol, FFAs in the co-culture medium, and butyrate significantly reduced them. Butyrate inhibited the phosphorylation of MAPKs, the activity of NF-κB in co-cultured macrophages, and suppressed lipase activity in co-cultured adipocytes. Lipase inhibitors significantly attenuated the production of TNF-α, MCP-1 and IL-6 in the co-culture medium as effectively as butyrate. Butyrate suppressed the protein production of adipose triglyceride lipase, hormone sensitive lipase, and fatty acid-binding protein 4 in co-cultured adipocytes. Pertussis toxin, which is known to block GPR41 completely, inhibited the antilipolysis effect of butyrate.

CONCLUSION: Butyrate suppresses inflammatory responses generated by the interaction of adipocytes and macrophages through reduced lipolysis and inhibition of inflammatory signaling.

Abstract  The aim of the study was to investigate the in vivo epigenetic influences of dietary butyrate supplementation on the acetylation state of core histones and the activity of drug-metabolising microsomal cytochrome P450 (CYP) enzymes in the liver of broiler chickens in the starter period. One-day-old Ross 308 broilers were fed a starter diet without or with sodium butyrate (1.5 g/kg feed) for 21 days. After slaughtering, nucleus and microsome fractions were isolated from the exsanguinated liver by multi-step differential centrifugation. Histone acetylation level was detected from hepatocyte nuclei by Western blotting, while microsomal CYP activity was examined by specific enzyme assays. Hyperacetylation of hepatic histone H2A at lysine 5 was observed after butyrate supplementation, providing modifications in the epigenetic regulation of cell function. No significant changes could be found in the acetylation state of the other core histones at the acetylation sites examined. Furthermore, butyrate did not cause any changes in the drugmetabolising activity of hepatic microsomal CYP2H and CYP3A37 enzymes, which are mainly involved in the biotransformation of most xenobiotics in chicken. These data indicate that supplementation of the diet with butyrate probably does not have any pharmacokinetic interactions with simultaneously applied xenobiotics.

Abstract  Colorectal cancer (CRC) is considered an estrogen-dependent malignancy, and intratissue estrogen concentration can be controlled by steroid sulfatase (STS). Little is known about changes in the expression of STS during the development of CRC. Therefore, we analysed the STS mRNA levels in primary colonic adenocarcinoma tissues and adjacent histopathologically unchanged colonic mucosa from patients who underwent radical colon resection (n=90). We found a statistically significant decrease in STS transcript levels in CRC (P=0.0453). Moreover, we found that sodium butyrate (NaBu) significantly upregulated STS transcript levels in DLD-1 and HCT116 CRC cells. Our results suggest that STS expression can be decreased in the process of large intestinal carcinogenesis. Moreover, we observed that NaBu might increase STS expression in CRC cells.

Abstract  BACKGROUND: Butyrate delivery to the large bowel may positively modulate commensal microbiota and enhance immunity.

OBJECTIVE: To determine the effects of increasing large bowel butyrate concentration through ingestion of butyrylated high amylose maize starch (HAMSB) on faecal biochemistry and microbiota, and markers of immunity in healthy active individuals.

DESIGN: Male and female volunteers were assigned randomly to consume either two doses of 20 g HAMSB (n = 23; age 37.9 +/- 7.8 y; mean +/- SD) or a low amylose maize starch (LAMS) (n = 18; age 36.9 = 9.5 y) twice daily for 28 days. Samples were collected on days 0, 10 and 28 for assessment of faecal bacterial groups, faecal biochemistry, serum cytokines and salivary antimicrobial proteins.

RESULTS: HAMSB led to relative increases in faecal free (45%; 12-86%; mean; 90% confidence interval; P = 0.02), bound (950%; 563-1564%; P < 0.01) and total butyrate (260%; 174-373%; P < 0.01) and faecal propionate (41%; 12-77%; P = 0.02) from day 0 to day 28 compared to LAMS. HAMSB was also associated with a relative 1.6-fold (1.2- to 2.0-fold; P < 0.01) and 2.5-fold (1.4- to 4.4-fold; P = 0.01) increase in plasma IL-10 and TNF-alpha but did not alter other indices of immunity. There were relative greater increases in faecal P. distasonis (81-fold (28- to 237-fold; P < 0.01) and F. prausnitzii (5.1-fold (2.1- to 12-fold; P < 0.01) in the HAMSB group.

CONCLUSIONS: HAMSB supplementation in healthy active individuals promotes the growth of bacteria that may improve bowel health and has only limited effects on plasma cytokines.

Abstract  Histone acetylation is one mechanism that promotes gene expression, and it increases during learning of various tasks. Specifically, novel taste consumption produces an increased acetylation of histone lysine residues in the insular cortex (IC), where protein synthesis is crucial during memory consolidation of conditioned taste aversion (CTA). However, the role of this elevated histone acetylation during CTA learning has not been examined directly. Thus, the present study investigated the effects of sodium butyrate (NaBu), a histone deacetylase inhibitor, injected into the IC during CTA acquisition. Male Wistar rats, IC bilaterally implanted, were injected 60 min before saccharine presentation, with a total volume of 0.5 µl of NaBu solution (100, 500, and 10 µg/0.5 µl) or saline; 30 min later animals were injected intraperitoneally with lithium chloride, a malaise-inducing drug. The next day, CTA retrieval was tested. No effects of NaBu were observed during acquisition or retrieval, but during extinction trials, a significant delay in aversive memory extinction was observed in the group injected with the lowest NaBu dose. This result indicates that NaBu in the IC strengthens CTA and delays aversive memory extinction, and suggests that histone acetylation could increase long-term taste-aversive memory strength.

Abstract  BACKGROUND: The inflammatory response after hepatic ischemia reperfusion (I/R) contributes to liver dysfunction and failure after transplantation. Butyrate is a four-carbon fatty acid, normally produced by bacterial fermentation of fiber in mammalian intestines, with anti-inflammatory activities. The purpose of the present study was to investigate the protective effect of butyrate preconditioning, if any, against hepatic I/R injury in rats and the underlying mechanisms involved.

METHODS: Male Sprague-Dawley rats were subjected to a partial (70%) hepatic ischemia for 60 min after pretreatment with either vehicle or butyrate, followed by 3, 6, and 24 h of reperfusion. Hepatic injury was evaluated by biochemical and histopathologic examinations. Neutrophil infiltration was measured by myeloperoxidase (MPO) activity. The expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (Elisa) and Real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The expression of nuclear factor kappa B (NF-κB) p65 was determined by immunohistochemistry and Western blot analysis.

RESULTS: Butyrate treatment markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathologic changes. The expression of tumor necrosis factor-alpha, interleukin-6, and myeloperoxidase activity was attenuated by butyrate. Butyrate also reduced I/R-induced nuclear translocation of NF-κB p65 in Kupffer cells.

CONCLUSION: Our results suggest that butyrate alleviates I/R-induced liver injury, possibly by suppressing inflammatory factors production and preventing NF-κB activation in Kupffer cells.

Abstract  Modifications of histone deacetylases (HDACs) may be involved in microglia-driven neuroinflammatory responses. Recent studies suggest that several inflammatory molecules can regulate the extent of neurodegeneration and regeneration in the central nervous system (CNS). In the present study, we investigated the effects of HDAC inhibitors (HDACi) valproic acid (VPA) and sodium butyrate (NaBut) on the release of prostaglandins (PGs) in lipopolysaccharide (LPS)-activated microglia. We found that VPA and NaBut significantly enhanced LPS-induced release of PGE2, PGD2 and 8-iso-PGF2α. In addition, both compounds increased cyclooxygenase-2 and microsomal prostaglandin E synthase immunoreactivity and gene expression in LPS-stimulated microglia. Interestingly, treatment of activated microglia with HDACi also enhanced the gene expression and the release of different pro-inflammatory cytokines. Microglia activation with LPS leads to IκB-α degradation, as well as p38, ERK1/2 and JNK MAPKs phosphorylation and thus activation, which is not affected by treatment with VPA and NaBut. Furthermore, VPA and NaBut treatment induced histone acetylation at H3-K18 in microglia. We suggest that VPA and NaBut-driven increase in PGs release in LPS-activated microglia might be regulated at the transcriptional level and involves histone hyperacetylation. Our data demonstrate that VPA and NaBut are able to modulate microglia responses to inflammatory insults and thus possibly can regulate the CNS degenerative and regenerative processes.

Abstract  Adult stem cells hold great promise for use in tissue repair and regeneration. Recently, adipose tissue-derived stem cells (ADSCs) were found to be an appealing alternative to bone marrow stem cells (BMSCs) for bone tissue engineering. The main benefit of ADSCs is that they can be easily and abundantly available from adipose tissue. However, our prior study discovered an important phenomenon that BMSCs have greater osteogenic potential than ADSCs in vitro and epigenetic regulation plays a critical role in runt-related transcription factor 2 (Runx2) expression and thus osteogenesis. In this study, we aimed to improve the osteogenic potential of ADSCs by histone deacetylase inhibitor sodium butyrate (NaBu). We found that NaBu promoted rat ADSC osteogenic differentiation by altering the epigenetic modifications on the Runx2 promoter.

Abstract  BACKGROUND & AIMS: Butyrate is a four-carbon fatty acid that presents anti-inflammatory, anti-oxidative and apoptotic properties in colon and several cell lines. Because atherosclerosis has important oxidative and inflammatory components, butyrate could reduce oxidation and inflammation, impairing atherogenesis. We evaluated the effects of butyrate supplementation of butyrate on atherosclerosis and its mechanisms of action.

METHODS AND RESULTS: ApoE knockout mice were fed on chow diet or 1% butyrate-supplemented chow diet (Butyrate) for 10 weeks to assess atherosclerosis lesions area and inflammatory status. Macrophage and endothelial cells were also pretreated with butyrate (0.5 mM) for 2 h before oxLDL stimulation to study oxLDL uptake and pro and anti-inflammatory cytokine production. Butyrate reduced atherosclerosis in the aorta by 50%. In the aortic valve, butyrate reduced CCL2, VCAM1 and MMP2 productions in the lesion site, resulting in a lower migration of macrophage and increased collagen depositions in the lesion and plaque stability. When EA.hy926 cells were pretreated with butyrate, oxLDL uptake, CD36, VCAM1, CCL2 TNF, IL1β and IL6 productions were reduced, whereas IL10 production was increased. These effects were accompanied by a lower activation of NFκB due to a lower nuclear translocation of the p65 subunit.

CONCLUSION: Oral butyrate is able to slow the progression of atherosclerosis by reducing adhesion and migration of macrophages and increasing plaque stability. These actions are linked to the reduction of CD36 in macrophages and endothelial cells, decreased pro-inflammatory cytokines and lower activation of NFκB all of these data support a possible role for butyrate as an atheroprotective agent.

Abstract  OBJECTIVE: Obesity is a health concern. Resistant starch (RS) type 2 from high-amylose maize (HAM-RS2) and dietary sodium butyrate (SB) reduce abdominal fat in rodents. RS treatment is associated with increased gut hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), but it is not known if SB increases these hormones.

DESIGN AND METHODS: This was investigated in a 2 × 2 rat study with HAM-RS2 (0 or 28% weight) and dietary sodium butyrate (0 and 3.2%) resulting in isocaloric treatments: energy control (EC), sodium butyrate (SB), HAM-RS2 (RS), and the combination (SBRS).

RESULTS: RS and SB reduced abdominal fat and the combination reduced abdominal fat compared to SB and RS. RS was associated with increased fermentation in the cecum. Serum PYY and GLP-1 total were increased with RS treatment. RS treatment was associated with increased cecal butyrate produced from fermentation of RS, but there was no cecal increase for dietary SB.

CONCLUSIONS: SB after its absorption into the blood appears to not affect production of PYY and GLP-1, while butyrate from fermentation in the cecum promotes increased PYY and GLP-1. Future studies with lower doses of RS and SB are warranted and the combination may be beneficial for human health.

Abstract  The aim of this study was to determine whether dietary Na-butyrate supplementation affects butyrate and glucose oxidation by ruminal epithelial preparations and whether this effect can be acutely modulated by substrate (glucose and butyrate) supply. Eighteen Suffolk wether lambs (6 lambs/treatment) were blocked by body weight and, within block, randomly assigned to the control treatment (CON) or to diets containing differing Na-butyrate inclusion rates (1.58 or 3.16%) equating to 1.25 (B1.25), and 2.50% (B2.50) butyrate on a dry matter basis, respectively. All lambs received their diet for a period of 14 d. After dietary adaptation, lambs were killed and the ruminal epithelium was harvested from the ventral sac, minced finely, and used for in vitro incubations. Incubation medium contained either a constant concentration of glucose (4 mM) with increasing butyrate concentrations (0, 5, 15, 25, or 40 mM) or a constant butyrate concentration (15 mM) with increasing glucose concentrations (0, 1, 2, 4, or 8 mM) to allow for the evaluation of whether acute changes in the concentration of metabolic substrates affect the oxidation of glucose and butyrate. We observed no interactions between the in vivo and in vitro treatments. Increasing dietary butyrate supplementation linearly decreased glucose oxidation by ruminal epithelial preparations, but had no effect on butyrate oxidation. Increasing butyrate concentration in vitro decreased (cubic effect) glucose oxidation when butyrate concentration ranged between 5 and 15 mM; however, glucose oxidation was increased with a butyrate concentration of 40 mM. Butyrate oxidation decreased (cubic effect) as glucose concentration increased from 1 to 4 mM; however, butyrate oxidation increased when glucose was included at 8mM. The results of this study demonstrate that dietary butyrate supplementation can decrease glucose oxidation by the ruminal epithelium, but the relative supply of glucose and butyrate has a pronounced effect on substrate oxidation.

Abstract  BACKGROUND/PURPOSE: The present study was designed to investigate the potential of sodium butyrate, a histone deacetylase (HDAC) inhibitor, in chronic constriction injury (CCI)-induced neuropathic pain in rats.

MATERIALS AND METHODS: Neuropathic pain was induced by placing four loose ligatures around the sciatic nerve. Acetone drop, Von frey hair, pin prick and hot plate tests were performed to assess cold allodynia, mechanical allodynia, and mechanical and heat hyperalgesia, respectively. The level of tumor necrosis factor (TNF)-α was measured in the sciatic nerve as an inflammatory marker.

RESULTS: CCI was associated with the development of cold allodynia, mechanical allodynia, and mechanical and heat hyperalgesia, along with an increase in TNF-α level. Administration of sodium butyrate (200 and 400 mg/kg, oral) for 14 days in CCI-subjected rats significantly attenuated behavior related to injury-induced pain and the increase in TNF-α level.

CONCLUSION: It may be concluded that the anti-inflammatory actions mediated by sodium butyrate are responsible for its beneficial effects in neuropathic pain in rats.