Fructose Reduces Mitochondrial Metabolism and Increases Extracellular BCAA during Insulin Resistance in C2C12 Myotubes.

Fructose is a commonly consumed monosaccharide implicated in developing several metabolic diseases. Previously, elevated branched-chain amino acids (BCAA) have been correlated with the severity of insulin resistance. Most recently, the effect of fructose consumption on the downregulation of BCAA catabolic enzymes was observed. Thus, this mechanistic study investigated the effects of physiologically attainable levels of fructose, both with and without concurrent insulin resistance, in a myotube model of skeletal muscle. METHODS: C2C12 mouse myoblasts were treated with fructose at a concentration of 100 µM (which approximates physiologically attainable concentrations in peripheral circulation) both with and without hyperinsulinemic-mediated insulin resistance. Gene expression was assessed by qRT-PCR, and protein expression was assessed by Western blot. Oxygen consumption rate and extracellular acidification rate were used to assess mitochondrial oxidative and glycolytic metabolism, respectively. Liquid chromatography-mass spectrometry was utilized to analyze leucine, isoleucine and valine concentration values. RESULTS: Fructose significantly reduced peak glycolytic and peak mitochondrial metabolism without altering related gene or protein expression. Similarly, no effect of fructose on BCAA catabolic enzymes was observed; however, fructose treatment resulted in elevated total extracellular BCAA in insulin-resistant cells. DISCUSSION: Collectively, these observations demonstrate that fructose at physiologically attainable levels does not appear to alter insulin sensitivity or BCAA catabolic potential in cultured myotubes. However, fructose may depress peak cell metabolism and BCAA utilization during insulin resistance.

Mice learn to identify and discriminate sugar solutions based on odor cues.

This study examined how olfaction impacts ingestive responses of mice to sugar solutions. Experiment 1 asked whether naïve C57BL/6 (B6) mice could identify 1 M glucose, fructose, or sucrose solutions based on odor cues, during a 30-min 2-bottle acceptability test. We tested mice both before and after they were rendered anosmic with ZnSO4 treatment. We used 2 indirect measures of odor-mediated response: number of trials initiated and latency to initiate licking. Before ZnSO4 treatment, the mice learned how to identify 1 M glucose and fructose (but not sucrose) solutions based on odor cues. ZnSO4 treatment eliminated their ability to identify the glucose and fructose solutions. Experiment 2 asked whether 2 d of exposure to a 1 M glucose, fructose, or sucrose solution improved the identification of the same sugar solution. Following exposure, the B6 mice identified all 3 sugar solutions based on odor cues. Experiment 3 asked whether T1R3 knockout mice (i.e. mice lacking the T1R3 subunit of the T1R2 + R3 sweet taste receptor) could learn to discriminate 0.44 M glucose and fructose solutions based on odor cues. All mice were subjected to a 1-h preference test, both before and after exposure to the 0.44 M glucose and fructose solutions. During exposure, the experimental mice received ZnSO4 treatment, whereas the control mice received saline treatment. Before exposure, neither type of mouse preferred the glucose solution. After exposure, the control mice preferred the glucose solution, whereas the experimental mice did not. Our results reveal that mice can learn to use odor cues to identify and discriminate between sugar solutions.

Inhibitory effect of organogermanium compound 3-(trihydroxygermyl)propanoic acid on fructose-induced glycation of amino compounds.

3-(Trihydroxygermyl)propanoic acid (THGP), a hydrolysate of poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132, also known as repagermanium), can inhibit glycation between glucose/ribose and amino compounds. In addition, THGP may inhibit glycation by inhibiting reactions that occur after Amadori rearrangement and inducing the reversible solubilization of AGEs. In this study, we first investigated the effects and mechanisms on the glycation of fructose and amino compounds by THGP, as a greater reactivity was obtained with fructose than with glucose. Unlike other anti-glycation materials, THGP can form a complex with fructose, the initial compound of glycation. THGP also inhibited the production of AGEs and suppressed the reduction of fructose in a reaction between fructose and arginine. These results indicate that THGP forms a complex with cyclic fructose possessing a cis-diol structure at a reducing end, and that it suppresses the ring-opening of fructose and the progress of the initial glycation reaction. We next tried to evaluate the suppressive effect of glucosyl hesperidin (GHes) and THGP on the reaction of glycation between fructose and collagen. Both compounds effectively reduced the production of AGEs individually, and the combination of them led to a synergistic suppression. Therefore, through combination with other antiglycation materials, THGP may cooperatively exhibit glycation-inhibitory effects and be able to suppress the AGE production.

Effects of Liquid Fructose Supplementation and Chronic Unpredictable Stress on Uterine Contractile Activity in Nonpregnant Rats.

Increased fructose consumption and chronic stress, the major characteristics of modern lifestyle, impact human health; however, the consequences of their combination on the uterus remain understudied. In this study, we investigated contractile activity, morphology, and intracellular activity of antioxidant enzymes in uteri from virgin Wistar rats subjected to liquid fructose supplementation and/or unpredictable stress over 9 weeks. Contractile activity and uterine response to oxytocin or adrenaline were examined ex vivo using isolated bath chambers. Fructose supplementation, irrespective of stress, affected uterine morphology by increasing endometrium while decreasing myometrium volume density, attenuated uterine response to increasing doses of oxytocin, and increased glutathione peroxidase activity. Stress, irrespective of fructose, attenuated dose-dependent adrenaline-induced uterine relaxation. Stress, when applied solely, decreased mitochondrial superoxide dismutase activity. In the combined treatment, irregular estrous cycles and both reduced response to oxytocin and to adrenaline (as a consequence of fructose consumption and exposure to stress), along with fructose-related alteration of uterine morphology, were detected. In conclusion, fructose and stress affect uterine contractile activity, irrespective of each other, by inducing completely distinct responses in isolated uteri. In the combined treatment, the effects of both factors were evident, suggesting that the combination exerts more detrimental effects on the uterus than each factor individually.

Effects of D-Allulose with Sucrose Beverage on Glucose Tolerance and Insulin Levels among Thai Healthy Volunteers.

D-Allulose has blood glucose suppression effects in both animal and clinical studies. The mechanism mediating glucose suppression in animals is controlled by several actions including the inhibition of sucrase. To investigate the dose-response effects of D-allulose with a sucrose beverage on glucose tolerance and insulin levels using Thai volunteers. This was a prospective, randomized, double-blinded, crossover study. Subjects had five oral sucrose tolerance tests (OSTT) with escalating doses of D-allulose (0, 2.5, 5, 7.5 or 10 g) with a 50 g sucrose beverage in a random order once a week for five consecutive weeks. The five drinks were consumed in a random order; the order being blinded for both subjects and investigators. Blood samples were drawn immediately before consumption and at 30, 60, 90 and 120 min after consumption of the study product for measurement of plasma glucose and insulin levels. Thirty healthy subjects (11 men and 19 women) completed the study. The peak postprandial glucose (PePPG) and insulin levels (PePPI) were lower when D-allulose was added in a dose-dependent manner. The lowest plasma glucose and insulin levels occurred at 120 min after OSTT in all five products and they were raised when D-allulose was added in a dose-dependent manner. D-Allulose has a suppression response on glucose and insulin shown by the decrease in postprandial plasma glucose and insulin levels following the addition of D-allulose to sucrose in a dose-dependent manner. The more D-allulose added, the less marked the glucose and insulin response occurred.

Carbon substrates promotes stress resistance and drug tolerance in clinical isolates of Candida tropicalis.

Candida tropicalis is a human pathogen and one of the most prevalent non-Candida albicans Candida (NCAC) species causing invasive infections. Azole antifungal resistance in C. tropicalis is also gradually increasing with the increasing incidence of infections. The pathogenic success of C. tropicalis depends on its effective response in the host microenvironment. To become a successful pathogen, cellular metabolism, and physiological status determine the ability of the pathogen to counter diverse stresses inside the host. However, to date, limited knowledge is available on the impact of carbon substrate metabolism on stress adaptation and azole resistance in C. tropicalis. In this study, we determined the impact of glucose, fructose, and sucrose as the sole carbon source on the fluconazole resistance and osmotic (NaCl), oxidative (H2O2) stress adaptation in C. tropicalis clinical isolates. We confirmed that the abundance of carbon substrates influences or increases drug resistance and osmotic and oxidative stress tolerance in C. tropicalis. Additionally, both azole-resistant and susceptible isolates showed similar stress adaptation phenotypes, confirming the equal efficiency of becoming successful pathogens irrespective of drug susceptibility profile. To the best of our knowledge, our study is the first on C. tropicalis to demonstrate the direct relation between carbon substrate metabolism and stress tolerance or drug resistance.

Knocking Out Sodium Glucose-Linked Transporter 5 Prevents Fructose-Induced Renal Oxidative Stress and Salt-Sensitive Hypertension.

BACKGROUND: A fructose high-salt (FHS) diet increases systolic blood pressure and Ang II (angiotensin II)-stimulated proximal tubule (PT) superoxide (O2-) production. These increases are prevented by scavenging O2- or an Ang II type 1 receptor antagonist. SGLT4 (sodium glucose-linked cotransporters 4) and SGLT5 are implicated in PT fructose reabsorption, but their roles in fructose-induced hypertension are unclear. We hypothesized that PT fructose reabsorption by SGLT5 initiates a genetic program enhancing Ang II-stimulated oxidative stress in males and females, thereby causing fructose-induced salt-sensitive hypertension. METHODS: We measured systolic blood pressure in male and female Sprague-Dawley (wild type [WT]), SGLT4 knockout (-/-), and SGLT5-/- rats. Then, we measured basal and Ang II-stimulated (37 nmol/L) O2- production by PTs and conducted gene coexpression network analysis. RESULTS: In male WT and female WT rats, FHS increased systolic blood pressure by 15±3 (n=7; P<0.0027) and 17±4 mm Hg (n=9; P<0.0037), respectively. Male and female SGLT4-/- had similar increases. Systolic blood pressure was unchanged by FHS in male and female SGLT5-/-. In male WT and female WT fed FHS, Ang II stimulated O2- production by 14±5 (n=6; P<0.0493) and 8±3 relative light units/µg protein/s (n=7; P<0.0218), respectively. The responses of SGTL4-/- were similar. Ang II did not stimulate O2- production in tubules from SGLT5-/-. Five gene coexpression modules were correlated with FHS. These correlations were completely blunted in SGLT5-/- and partially blunted by chronically scavenging O2- with tempol. CONCLUSIONS: SGLT5-mediated PT fructose reabsorption is required for FHS to augment Ang II-stimulated proximal nephron O2- production, and increases in PT oxidative stress likely contribute to FHS-induced hypertension.

Enhancing Targeted Photodynamic Therapy: Star-Shaped Glycopolymeric Photosensitizers for Improved Selectivity and Efficacy.

Targeted photodynamic therapy (PDT) offers advantages over nontargeted approaches, including improved selectivity, efficacy, and reduced side effects. This study developed star-shaped glycopolymeric photosensitizers using porphyrin-based initiators via ATRP. Incorporating a porphyrin core gave the polymers fluorescence and ROS generation, while adding fructose improved solubility and targeting capabilities. The photosensitizers had high light absorption, singlet oxygen production, specificity, low dark toxicity, and biocompatibility. The glycopolymers with longer sugar arms and higher density showed better uptake on MCF-7 and MDA-MB-468 cells compared to HeLa cells, indicating enhanced targeting capabilities. Inhibition of endocytosis confirmed the importance of the GLUT5 receptor. The resulting polymers exhibited good cytocompatibility under dark conditions and satisfactory PDT under light irradiation. Interestingly, the polymers containing fructose have a GLUT5-dependent elimination effect on the MCF-7 and MDA-MB-468 cells. The intracellular ROS production followed a similar pattern, indicating that the fructose polymer exhibits specific targeting toward cells with GLUT5 receptors.

Discrimination of cellulose microparticles in rats.

Oral perception of food particles is important in mastication and swallowing. However, the mechanism underlying particle perception remains poorly understood because of the lack of suitable experimental systems. We evaluated microparticle perception in rats utilizing insoluble cellulose particles of varying diameters (20-170 µm). The cellulose additives have polycrystalline morphologies and contain smaller crushed particles. The filtrate containing 20 µm particles at a concentration of 1.6% was passed through 3 µm pore-size filter paper, and numerous small particles equivalent to a 0.25 mM soluble solution were observed. In two-bottle preference tests, rats showed no innate preference or avoidance of particles of any size at concentrations ranging from 0.05-1.6%. Next, conditioned preference learning tests employing 8% glucose and fructose solutions were performed. After being repeatedly presented with glucose and fructose solutions containing particles of different sizes (170 and 20 µm particles or 20 µm filtrate) at a concentration of 1.6%, the rats preferred particles in glucose solution even without glucose presentation. Intriguingly, rats preferred the filtrate following repeated presentations of glucose-containing filtrate and water containing fructose. These results suggest that rats can distinguish microparticles in water. The preference learning test is useful for analyzing particle perception mechanisms in mammals.

Fructose Potentiates Bone Loss and Marrow Adipose Tissue Accumulation by Inhibiting Adenosine 5'-Monophosphate-Activated Protein Kinase in Mesenchymal Stem Cells.

Increased fructose consumption has been elucidated to contribute to metabolic diseases. Bone is a dynamic organ that undergoes constant remodeling. However, the effects of fructose on bone health are still in dispute. Here, we identified fructose deteriorated bone mineral density while promoting the abundance of bone marrow adipose tissue. Fructose remarkably promoted the bone marrow mesenchymal stem cells' (BMMSCs) adipogenic commitment at the expense of osteogenic commitment. Fructose boosted the glycolysis of BMMSCs and inhibited phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK), which played a crucial role in bone-fat alteration. Our results suggested that fructose potentiated bone loss and marrow adipose tissue accumulation by suppressing AMPK activation in BMMSCs. Understanding fructose which affected bone metabolism was thus of primary importance in order to establish preventative measures or treatments for this condition.

Effect of Administration of Selenium Nanoparticles Synthesized Using Onion Extract on Biochemical and Inflammatory Parameters in Mice Fed with High-Fructose Diet: In Vivo and In Silico Analysis.

Fructose consumption has increased globally and has been linked to obesity, insulin resistance, and diabetes. Selenium nanoparticles (SeNPs) can regulate glucose and lipid concentrations and have immunoregulatory properties. Four study groups (n = 7/group) of eight-week-old male mice (Balb/c) were formed for this investigation. One group received a standard diet (C), another standard diet plus SeNPs (C + SeNPs), a high fructose diet (F), and a group with a high fructose diet plus SeNPs (F + SeNPs). Weight, glucose, triglycerides, and cholesterol were evaluated. In the end, mice were sacrificed, blood samples were obtained to assess cytokine profile, and liver, kidney, and pancreas were removed for histological examination. The study was complemented with an in silico analysis where the CTD, STITCH, ToppGene Suite, ShinyGO 0.76.3 databases, and Cytoscape software were implemented. The results of in vivo analysis showed that SeNPs regulated biochemical parameters and showed anti-inflammatory effects by decreasing the concentrations of TNF-alpha, IL-1beta, and IFN-gamma and increasing IL-10. No damage was observed in the studied organs. In addition, SeNPs regulate oxidative stress, preserve cell organelles, and regulate metabolic pathways to avoid the adverse effects of fructose consumption, according to bioinformatics analysis. In conclusion, SeNPs protect against the undesirable effects of a diet rich in fructose.

Angiotensin II-stimulated proximal nephron superoxide production and fructose-induced salt-sensitive hypertension.

Angiotensin II (ANG II) increases proximal tubule superoxide (O2-) production more in rats fed a 20% fructose normal-salt diet compared with rats fed a 20% glucose normal-salt diet. A 20% fructose high-salt diet (FHS) increases systolic blood pressure (SBP), whereas a 20% glucose high-salt diet (GHS) does not. However, it is unclear whether FHS enhances ANG II-induced oxidative stress in proximal tubules and whether this contributes to increases in blood pressure in this model. We hypothesized that FHS augments the ability of ANG II to stimulate O2- production by proximal tubules, and this contributes to fructose-induced salt-sensitive hypertension. We measured SBP in male Sprague-Dawley rats fed FHS and GHS and determined the effects of 3 mM tempol and 50 mg/kg losartan for 7 days. We then measured basal and ANG II-stimulated (3.7 × 10-8 M) O2- production by proximal tubule suspensions and the role of protein kinase C. FHS increased SBP by 27 ± 5 mmHg (n = 6, P < 0.006) but GHS did not. Rats fed FHS + tempol and GHS + tempol showed no significant increases in SBP. ANG II increased O2- production by 11 ± 1 relative light units/µg protein/s in proximal tubules from FHS-fed rats (n = 6, P < 0.05) but not in tubules from rats fed GHS. ANG II did not significantly stimulate O2- production by proximal tubules from rats fed FHS + tempol or FHS + losartan. The protein kinase C inhibitor Gö6976 blunted ANG II-stimulated O2- production. In conclusion, FHS enhances the sensitivity of proximal tubule O2- production to ANG II, and this contributes to fructose-induced salt-sensitive hypertension.NEW & NOTEWORTHY A diet containing amounts of fructose consumed by 17 million Americans causes salt-sensitive hypertension. Oxidative stress is an initiating cause of this model of fructose-induced salt-sensitive hypertension increasing blood pressure. This salt-sensitive hypertension is prevented by losartan and thus is angiotensin II (ANG II) dependent. Fructose-induced salt-sensitive hypertension depends on ANG II stimulating oxidative stress in the proximal tubule. A fructose/high-salt diet augments the ability of ANG II to stimulate proximal tubule O2- via protein kinase C.

GLUT5, GLUT7, and GLUT11 expression and Bcl-2/Bax ratio on Breast Cancer Cell Line MCF-7 Treated with Fructose and Glucose.

OBJECTIVE: Fructose and glucose are types of sugars commonly found in the diet that have been linked to cancer development. Glucose transporters (GLUTs) are facilitating the uptake of these hexoses. Expression of GLUT5 is higher in cancer cells than in healthy tissue. GLUT7 and GLUT11 facilitate the transport of glucose and fructose; however, their expression in breast cancer has not been extensively studied. The Bcl-2 family has been known as a regulator of the cell's survival and death. Here, we investigated the effect of the fructose-glucose combination in MCF-7 breast cancer cells on the viability, migration, and expression of GLUT5, GLUT7, GLUT11, and Bcl-2/Bax ratio. METHODS: Breast cancer cells MCF-7 were treated with fructose, glucose, and combinations of fructose:glucose (75%:25%, 50%:50%, 25%:75%). Cell viability was assessed using an MTT test. Cell migration was examined with a wound-healing assay. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the mRNA expression of GLUT5, GLUT7, GLUT11, and Bcl-2/Bax. RESULTS: The viability and migration of MCF-7 breast cancer cells elevated when treated with a combination of fructose and glucose, and glucose alone, compared to fructose alone. The expression levels of GLUT5 and GLUT7 were highest in combination of fructose:glucose (75%:25%). Conversely, the expression of GLUT11 was consistently low across all treated media. The highest Bcl-2/Bax ratio was shown in fructose:glucose combination (25%:75%). CONCLUSION: The viability, migration, and Bcl-2/Bax ratio are enhanced in the combination media with higher glucose. In contrast, when the fructose composition was higher in the media, expression of GLUT5 and GLUT7 increased.

High-fructose consumption suppresses insulin signaling pathway accompanied by activation of macrophage and apoptotic markers in rat testis.

Dietary high-fructose may cause metabolic disturbances; however, its effect on the reproductive system is little understood. The insulin signaling pathway is critical in testicular development, maintenance of microcirculation and spermatogenesis. Therefore, in this study, we aimed to investigate the impact of dietary high-fructose on insulin signaling pathway as well as macrophage and apoptotic markers in testicular tissue of rats. Fructose was administered to male Wistar rats as a 20% solution in drinking water for fifteen-week. Gene expression of ir-ß, irs-1, irs-2, pi3k, akt, mtor, and enos in the testicular samples was determined by real-time PCR. Protein expression of IR, IRS-1, IRS-2, PI3K, Akt, phospho-Akt (p-Akt), mTOR, eNOS, phospho-eNOS (p-eNOS), and GLUT5 was established by analysis of Western Blot. Testicular expression of occludin, CD163, CD68, caspase-8, and caspase-3 was analyzed by using immunohistochemical assay. Testicular level of fructose was measured by colorimetric method. Dietary high-fructose decreased mRNA expressions of irs-1, irs-2, pi3k, and mtor in the testicular tissue of rats. Also, this dietary intervention impaired protein expressions of IR, IRS-1, IRS-2, PI3K, p-Akt, mTOR, eNOS, and p-eNOS as well as p-Akt/Akt and p-eNOS/eNOS ratios in the testis of rats. However, a high-fructose diet increased the expression of CD163, CD68, caspase-8 and caspase-3, but decreased that of occludin, in the testicular tissue of rats. The high-fructose consumption in rats suppresses testicular insulin signaling but activates macrophages-related factors and apoptotic markers. These changes induced by dietary fructose could be related to male reproductive dysfunction.

Aerobic exercise prevents cardiomyocyte damage caused by oxidative stress in early cardiovascular disease by increasing vascularity while L-arginine supplementation prevents it by increasing activation of the enzyme nitric oxide synthase.

L-Arginine and chronic exercise reduce oxidative stress. However, it is unclear how they affect cardiomyocytes during cardiovascular disease (CVD) development. The aim of this research was to investigate the possible effects of L-arginine supplementation and aerobic training on systemic oxidative stress and their consequences on cardiomyocytes during cardiometabolic disease onset caused by excess fructose. Wistar rats were allocated into four groups: control (C), fructose (F, 10% fructose in water), fructose training (FT; moderate running, 50-70% of the maximal velocity), and fructose arginine (FA; 880 mg/kg/day). Fructose was given for two weeks and fructose plus treatments for the subsequent eight weeks. Body composition, blood glucose, insulin, lipid profile, lipid peroxidation, nitrite, metalloproteinase-2 (MMP-2) activity, left ventricle histological changes, microRNA-126, -195, and -146, eNOS, p-eNOS, and TNF-α expressions were analyzed. Higher abdominal fat mass, triacylglycerol level, and insulin level were observed in the F group, and both treatments reversed these alterations. Myocardial vascularization was impaired in fructose-fed groups, except in FT. Cardiomyocyte hypertrophy was observed in all fructose-fed groups. TNF-α levels were higher in fructose-fed groups than in the C group, and p-eNOS levels were higher in the FA than in the C and F groups. Lipid peroxidation was higher in the F group than in the FT and C groups. During CVD onset, moderate aerobic exercise reduced lipid peroxidation, and both training and L-arginine prevented metabolic changes caused by excessive fructose. Myocardial vascularization was impaired by fructose, and cardiomyocyte hypertrophy appeared to be influenced by pro-inflammatory and oxidative environments.

Expression of aldose reductase in mouse endometrial epithelial cells and its role in sperm capacitation.

The survival, motility and capacitation of sperm in the female reproductive tract are important prerequisites for fertilization. The uterus is the main location for sperm capacitation. One of the most important physiological functions of the endometrial epithelium is to create a suitable uterine environment under the regulation of ovarian hormones, to ensure sperm capacitation. The composition of uterine fluid directly affects sperm capacitation. Fructose is an important component of semen that supports sperm viability and motility. Aldose reductase, a rate-limiting enzyme in the polyol pathway, metabolizes sorbitol and fructose, thereby supplying cells with necessary energy for functional activities. Existing studies have reported the presence aldose reductase in the endometrium, leading us to hypothesize that its expression in endometrial epithelium might promote sperm capacitation by maintaining the uterine environment. Yet, the mechanism of regulation has not been clarified. In this study, we investigated the expression of aldose reductase in mouse endometrial epithelium and its potential role in sperm capacitation. We initially investigated the periodic characteristics of glucose, fructose and sorbitol in uterine fluid. We then studied the temporal and spatial characteristics of aldose reductase in the endometrial epithelium. Next, we examined the effect of aldose reductase on glucose, fructose and sorbitol in uterine fluid. Finally, we explored the effect of aldose reductase on sperm capacitation and fertilization. The results showed that glucose and fructose content in uterine fluid and the expression of aldose reductase fluctuated periodically during physiological periods. Inhibition of aldose reductase in the endometrial epithelium interfered with sperm capacitation and fertilization by reducing the fructose levels in the uterine fluid. To conclude, the aldose reductase-mediated polyol pathway in endometrial epithelial cells is essential to maintain an appropriate fructose environment in the uterine fluid for sperm capacitation and fertilization.

Different patterns of germination inhibition by carvacrol and thymol in Bacillus subtilis spores.

This study aimed to clarify how the phenolic monoterpene carvacrol and its structural isomer thymol both as essential oil components (EOCs) inhibit the germination of Bacillus subtilis spore. Germination was evaluated by the OD600 reduction rate in a growth medium and phosphate buffer containing either l-alanine (l-Ala) system or l-asparagine, d-glucose, d-fructose plus KCl (AGFK) system. The germination of the wild-type spores in the Trypticase Soy broth (TSB) was found to be greatly inhibited by thymol than by carvacrol. Such a difference in the germination inhibition was confirmed by the dipicolinic acid (DPA) release from germinating spores in the AGFK buffer system, but not in the l-Ala system. Similar to the wild-type spores, no difference in the inhibitory activity between the EOCs was also indicated with the gerB, gerK-deletion mutant spores in the l-Ala buffer system and the above substantial difference was also done with the gerA-deleted mutant spores in the AGFK. Fructose was found to release spores from the EOC inhibition and inversely even stimulated. Increased concentrations of glucose and fructose partially suppressed the germination inhibition by carvacrol. The results obtained should contribute to the elucidation of the control effects of these EOCs on bacterial spores in foods.

Effects of Lombok Island's local moringa (Moringa oleifera) leaf powder on the decrease of liver fructose levels and GLUT5 expression in albino rats (Rattus novergicus) fed a high fructose diet.

Background: Consumed fructose enters enterocytes of the intestinal epithelial apical membrane mediated by glucose transporter 5 (GLUT5). Aim: To determine the effects of Lombok Island's local Moringa leaf powder on reducing liver fructose levels and GLUT5 expression in the small intestine of albino rats (Rattus novergicus) fed a high-fructose diet. Methods: Moringa leaf (Moringa oleifera) was obtained from Lombok Island, Indonesia. Subsequently, 30 male albino rats (R. novergicus) were used, divided into the normal group (NG), treatment group 1 (T1G), treatment group 2 (T2G), Quercetin group (QG), Moringa group (MG). Quercetin and moringa leaf powder (M. oleifera) was administered at 50 and 500 mg/kgbw for 28 days. Enzyme-linked immunosorbent assay (Elisa) method was used to examine liver fructose levels. The observation of GLUT5 expression in the small intestine was performed by the Immunofluorescence method. Results: The ANOVA test proved that there are significant differences (p < 0.005) in liver fructose levels in all groups. Further post hoc tests show no significant difference (p > 0.005) in liver fructose levels in rats fed a high fructose diet in T1G and T2G with QG and MG rats. However, Moringa leaf powder reduces liver fructose levels by 32.1% and 17.2% in T1G and T2G rats, respectively. The ANOVA test showed a significant difference (p < 0.005) in the expression of GLUT5 in all groups. Further post hoc tests showed a significant difference (p < 0.005) in the expression of GLUT5 in the duodenum, jejunum, and ileum between the NG and the T1G rats. Meanwhile, in T2G rats, significant differences were only found in the jejunum. Moringa leaf powder reduces GLUT5 expression in T1G rats by 44.5%, 59.5%, and 57.2% in the duodenum, jejunum, and ileum, whereas in T2G rats is by 33.5%, 50.2%, and 48.1%, respectively. Conclusion: The administration of local moringa (M. oleifera) leaf powder in Lombok Island had an effect on reducing GLUT5 expression in the small intestine, however, did not in liver fructose levels of albino rats (R. novergicus) fed a high-fructose diet.

Narrative Review of Topiramate: Clinical Uses and Pharmacological Considerations.

Due to the diverse mechanisms of action of antiseizure drugs, there has been a rise in prescriptions of these drugs for non-epileptic pathologies. One drug that is now being used for a variety of conditions is topiramate. This is a narrative review that used PubMed, Google Scholar, MEDLINE, and ScienceDirect to review literature on the clinical and pharmacologic properties of topiramate. Topiramate is a commonly prescribed second-generation antiseizure drug. The drug works through multiple pathways to prevent seizures. In this regard, topiramate blocks sodium and calcium voltage-gated channels, inhibits glutamate receptors, enhances gamma-aminobutyric acid (GABA) receptors, and inhibits carbonic anhydrase. Topiramate is approved by the Food and Drug Administration (FDA) for epilepsy treatment and migraine prophylaxis. Topiramate in combination with phentermine is also FDA-approved for weight loss in patients with a body mass index (BMI) > 30. The current target dosing for topiramate monotherapy is 400 mg/day and 100 mg/day to treat epilepsy and migraines, respectively. Commonly reported side effects include paresthesia, confusion, fatigue, dizziness, and change in taste. More uncommon and serious adverse effects can include acute glaucoma, metabolic acidosis, nephrolithiasis, hepatotoxicity, and teratogenicity. Related to a broad side effect profile, physicians prescribing this drug should routinely monitor for side effects and/or toxicity. The present investigation reviews various anti-seizure medications before summarizing indications of topiramate, off-label uses, pharmacodynamics, pharmacokinetics, adverse effects, and drug-drug interactions.

Fructose supplementation shifts rat brain metabolism in experimental migraine.

AIMS: We have previously demonstrated that fructose supplementation (FS), given in a scheme used for inducing metabolic syndrome (MS), elicited pain relief in the nitroglycerin (NTG)-elicited rat migraine model. Herein, we evaluated whether FS could reestablish the impaired metabolic pathways in NTG-injected rats. MAIN METHODS: Male Wistar rats (N = 40) were divided into two groups for receiving 10 % FS or tap water. After 45 days, they were subdivided into NTG-injected (10 mg/kg; 15 days) or controls. After the fourth NTG injection, 18F-fluorodeoxyglucose ([18F] FDG) micro-PET scanning was accomplished. The day after, euthanasia was performed, and blood was collected for glycemia and LDH analysis. The levels of energy molecules, TBARS, PGC-1α, and MCTS1 were evaluated in the brain cortices. The activated satellite glial cells (SGC) were assessed in the trigeminal ganglion (TG). KEY FINDINGS: There were no variations of glycemia or LDH serum levels. NTG-injected rats showed a significant increase in glucose uptake in the hypothalamus (HT) vs. NTG-free rats. The FS-NTG group showed increased metabolism in the superior colliculus (SC) vs. the NTG group. Moreover, the glucose uptake was amplified in the inferior colliculus (IC) of the FS-NTG vs. FS group. The cortical inosine levels were significantly higher in FS-NTG rats vs. NTG or FS groups, with no changes in TBARS or MCTS1 levels, despite a minor decrease of PGC1-α contents in the FS+NTG group. Finally, there was a significant increase of activated SGC around TG in the FS-NTG rats. SIGNIFICANCE: We provide novel evidence linking nutrition and metabolism with migraine.