scholarly journals Subchronic exposure to acrylamide affects colon mucin secretion in juvenile wistar rats

2016 ◽  
Vol 68 (3) ◽  
pp. 641-649 ◽  
Author(s):  
Ivana Koledin ◽  
Renata Kovac ◽  
Vesna Rajkovic ◽  
Milica Matavulj

Acrylamide (AA) is an important industrial chemical worldwide. AA also forms naturally in many high-carbohydrate foods (bread, French fries, coffee, etc.) when they are heated. Since AA is ubiquitous in the human diet, and more than one-third of the calories we take in each day come from foods with detectable levels of acrylamide, the aim of this study was to determine the effect of subchronic AA treatment on colon goblet cell mucin secretion. Male Wistar rats were gavaged with AA for 5 days a week for 21 days. The animals were divided into three groups that were gavaged with different AA concentrations (0, 25, 50 mg/kg/day). Colon samples were processed for histochemical (PAS-AB, HID-AB) and immunohistochemical (anti-rat MUC2 antibody) staining to visualize mucins in the goblet cells. AA treatment showed an alteration in mucin production and secretion in that the amount of all investigated mucin types dropped. More prominent changes were detected in the upper crypt part where a decreased number of goblet cell was observed. AA treatment elicited a significant reduction in neutral mucins, while acidic mucins showed linearly decreasing trend with respect to AA doses. Also, a linear reduction of MUC2 mucins was noticed. Sulfomucins were absent in the colon lower crypt in all experimental groups, while in the upper crypt both sulfo- and sialomucins were significantly decreased. The results of our study point to changes in the synthesis, differentiation and distribution of mucins after AA treatment, which can have adverse effect on colorectal health.

2007 ◽  
Vol 292 (1) ◽  
pp. L92-L98 ◽  
Author(s):  
Andrea H. Rossi ◽  
Wendy C. Salmon ◽  
Michael Chua ◽  
C. William Davis

Despite the general importance of Ca2+ signaling in signal transduction, and of goblet cell mucin hypersecretion in inflammatory pulmonary diseases, measurement of airway goblet cell intracellular Ca2+ (Ca[Formula: see text]) has not been reported. In this article, we describe the results of experiments measuring Ca[Formula: see text] in primary cultures of human bronchial goblet cells after stimulation with the purinergic agonist adenosine 5′- O-(3-thiotriphosphate) (ATPγS) and phorbol 12-myristate 13-acetate (PMA). Ca2+ signaling in human goblet cells after purinergic stimulation follows the classic paradigm of a Ca[Formula: see text] transient from a basal activity of 110 nM to a peak response of 260.1 ± 41.2 nM within 2 min, followed by a long superbasal plateau (155.3 ± 0.2 nM) between 10 and 15 min. The rise in Ca[Formula: see text] appears to result from a mobilization of intracellular stores, because the transient was nearly abolished by inhibition of PLC with the phosphatidylinositol-specific PLC inhibitor U-73122, and it was not affected significantly by removal of extracellular Ca2+. Loading goblet cells with BAPTA inhibited the ATPγS-induced Ca2+ transient by 86.0 ± 13.1%, relative to control. Finally, in contrast to the massive effects of high doses of PMA (300 nM) on mucin secretion from goblet cells, phorbol ester stimulated a small (27.1 ± 7% of the ATPγS control peak), brief rise in Ca[Formula: see text]. This diminutive signal likely denotes a local Ca2+ gradient, which may be associated with the mucin granule exocytotic process.


2018 ◽  
Vol 11 (13) ◽  
pp. 200
Author(s):  
Nurul Hidayah ◽  
Ketut Adnyana I ◽  
Ketut Adnyana I ◽  
Neng Fisheri ◽  
Neng Fisheri ◽  
...  

Objective: The prevalence of obesity increases each year globally. Multifactorial etiology of obesity requires therapy management including changing of diet and medicines. Some of obesity drugs have shown ineffectiveness and safety. The previous study showed that water extract of tamarind could reduce body weight (bw). This study aimed to test the activity fraction of water extract tamarind as antiobesity using high carbohydrate diet.Method: The preventive research of antiobesity had done by given water fraction and ethyl acetate fraction of water extract tamarind following with induced high carbohydrate diet during 6th weeks in male Wistar rats. The parameters had observed including consumption of food, body weight, weight of feces, volume of urine, total cholesterols, triglycerides, blood glucose, index of organs, and accumulation of body fat.Result: The ethyl acetate fraction at doses 4.5 mg/kg bw has shown significantly effect to decrease of total cholesterols level and decrease of triglycerides level at weeks 6 (p<0.05). All the tests of fraction have shown activity inhibition of increased body weight, decrease of appetite, total cholesterols, triglycerides, and blood glucose. Meanwhile, mechanism action of antiobesity as increase defecation, urination, and decrease index of organs and accumulation of body fat have not shown by all these test fractions.Conclusion: The ethyl acetate fraction at doses of 4.5 mg/kg bw can inhibit raising of body weight, decrease of total cholesterols, and triglycerides level greater than the other test groups, where increasing of these levels of blood biochemistry was closely related to the pathology of obesity.


Author(s):  
Hongyan Zhu ◽  
Rui Li ◽  
Su Zhou ◽  
Suhui Zhang ◽  
Yu Wang ◽  
...  

A ninety-day toxicity and toxicokinetics of flurochloridone (FLC) were studied in male Wistar rats with oral administration at doses of 3 mg/kg and 10 mg/kg respectively, following the previous study. Apparent toxicity to reproductive system of male rats was still observed at the dose of 10 mg/kg, trace amounts of FLC were still detected 24 hours after administration, testicular weight, epididymal weight and serum testosterone were significantly reduced and sperm abnormalities in epididymis were significantly increased. No abnormalities were found in 3 mg/kg group, it indicated that no-observed-adverse-effect level (NOAEL) of FLC in male rats was 3 mg/kg/day, far below the dose of 20 mg/kg/day reported by European Food Safety Authority (EFSA). Therefore, more attention should be paid to this herbicide.


1991 ◽  
Vol 65 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Susan J. Fairweather-Tait ◽  
Zoe Piper ◽  
S. Jemil A. Fatemi ◽  
Geoffrey R. Moore

Weanling male Wistar rats were fed for 28 d on a semi-synthetic diet containing normal (38 μg/g) or low (9 μg/g) levels of iron. They were given water or tea infusion (20 g leaves/I water) to drink. Two further groups were given a normal- or low-Fe diet containing added tea leaves (20 g/kg diet). At the end of the study period, all rats given the low-Fe diet were severely anaemic, as assessed by haemoglobin, packed cell volume and liver Fe. Those given tea or the diet with added tea leaves showed a greater degree of Fe depletion. The blood and liver aluminium levels were not increased as a result of consuming tea or tea leaves, despite the higher Al intakes. Fe deficiencyper sehad no effect on Al absorption or retention from tea. It was concluded that the Al in tea was very poorly absorbed but that tea, either in the form of an infusion or as tea leaves, had an adverse effect on Fe status


2007 ◽  
Vol 293 (5) ◽  
pp. C1445-C1454 ◽  
Author(s):  
Camille Ehre ◽  
Yunxiang Zhu ◽  
Lubna H. Abdullah ◽  
John Olsen ◽  
Keiichi I. Nakayama ◽  
...  

Airway goblet cell mucin secretion is controlled by agonist activation of P2Y2 purinoceptors, acting through Gq/PLC, inositol-1,4,5-trisphosphate (IP3), diacylglycerol, Ca2+ and protein kinase C (PKC). Previously, we showed that SPOC1 cells express cPKCα, nPKCδ, nPKCε, and nPKCη; of these, only nPKCδ translocated to the membrane in correlation with mucin secretion (Abdullah LH, Bundy JT, Ehre C, Davis CW. Am J Physiol Lung Physiol 285: L149–L160, 2003). We have verified these results and pursued the identity of the PKC effector isoform by testing the effects of altered PKC expression on regulated mucin release using SPOC1 cell and mouse models. SPOC1 cells overexpressing cPKCα, nPKCδ, and nPKCη had the same levels of ATPγS- and phorbol-1,2-myristate-13-acetate (PMA)-stimulated mucin secretion as the levels in empty retroviral vector expressing cells. Secretagogue-induced mucin secretion was elevated only in cells overexpressing nPKCε (14.6 and 23.5%, for ATPγS and PMA). Similarly, only SPOC1 cells infected with a kinase-deficient nPKCε exhibited the expected diminution of stimulated mucin secretion, relative to wild-type (WT) isoform overexpression. ATPγS-stimulated mucin secretion from isolated, perfused mouse tracheas was diminished in P2Y2-R null mice by 82% relative to WT mice, demonstrating the utility of mouse models in studies of regulated mucin secretion. Littermate WT and nPKCδ knockout (KO) mice had nearly identical levels of stimulated mucin secretion, whereas mucin release was nearly abolished in nPKCε KO mice relative to its WT littermates. We conclude that nPKCε is the effector isoform downstream of P2Y2-R activation in the goblet cell secretory response. The translocation of nPKCδ observed in activated cells is likely not related to mucin secretion but to some other aspect of goblet cell biology.


2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S38-S38
Author(s):  
Melinda Engevik ◽  
Wenly Ruan ◽  
Faith Ihekweazu ◽  
James Versalovic

Abstract Background The intestinal mucus layer serves as a critical interface between the environment and the host. Patients with inflammatory bowel disease (IBD), particularly ulcerative colitis, exhibit reduced synthesis and secretion of the mucus protein MUC2 and decreased mucus thickness. This in turn promotes immune activation and inflammation. The clinical relevance of the mucus layer emphasizes the need to address strategies to modulate this barrier. Although bifidobacteria represent only 3–6% of the healthy adult fecal microbiota, their presence has been associated with numerous health benefits, including bolstering mucus production. However, the molecular mechanisms that underlie these positive effects appear to be strain-specific and are not well defined. We hypothesized that the human-derived Bifidobacterium dentium would increase intestinal mucus synthesis and expulsion via specific metabolites. We also speculated that modulation of goblet cells would be beneficial during colitis. Methods & Results In silico genome analysis revealed that B. dentium lacked the enzymatic repertoire required for degradation of mucin glycans. Consistent with these findings, we found that B. dentium could not use mucin glycans as a primary carbon source in vitro. To examine mucus modulation in vivo, germ-free mice were mono-associated with live or heat-killed B. dentium. Live B. dentium mono-associated mice exhibited increased colonic expression of goblet cell markers Krüppel-Like Factor 4 (Klf4), Relmβ, trefoil factor 3 (Tff3), Muc2, and several mucin glycosyltransferases compared to both heat-killed B. dentium and germ-free counterparts. Likewise, live B. dentium mono-associated colon had increased acidic mucin-filled goblet cells as denoted by MUC2 and PAS-AB staining. In vitro, B. dentium secreted products, including acetate, were able to increase MUC2 levels in T84 cells, mouse colonoids and human colonoids. We also identified that B. dentium secreted products, such as GABA, stimulated autophagy-mediated calcium signaling and MUC2 release. To identify whether B. dentium could enhance MUC2 production in mice harboring a complete microbiota, specific pathogen free mice were treated with live B. dentium by oral gavage. Administration of B. dentium increased the inner mucus layer compared to controls. Moreover, in a TNBS model of colitis, B. dentium treated mice had increased goblet cell numbers and MUC2 mRNA. Mirroring these findings, B. dentium treated mice lost less weight, had improved histology and had decreased levels of TNF, KC (IL-8), and IL-6. Conclusions This work illustrates that B. dentium enhances the intestinal mucus layer and goblet cell function via upregulation of gene expression and autophagy signaling pathways with a net increase in mucin production. Ultimately, these pathways may be targeted for the development of novel therapeutics.


Author(s):  
Afisu Basiru ◽  
Ganiu Jimoh Akorede ◽  
Kehinde Soetan ◽  
Funsho O. Olayemi

Abstract Background Numerous uses of Waltheria indica plant such as antitrypanosomal, antibacterial and antimalarial effects have been reported. It has however been reported that most plants with antibacterial and antiprotozoal effects have adverse effect on male reproduction. Hence, we evaluated the effect of Waltheria indica root on male reproductive parameters. Methods Twenty adult male Wistar rats were randomly divided into four groups (n=5); A–D. Group A served as control group while groups B, C and D were administered with 200, 400 and 800 mg/Kg body weight of crude ethanolic extract of Waltheria indica root. After 28 days of administration, the rats were sacrificed and sperm parameters, sperm morphology, serum reproductive hormones and lipids were determined. Results There was a significant reduction in sperm count and motility as well as significant increase in percentage abnormal sperm cell (p<0.001) at the 400 and 800 mg/kg BW. The serum levels of testosterone was also significantly reduced while total cholesterol increased significantly (p<0.05) at the highest dose. Conclusion Waltheria indica root has adverse effect on male reproduction through reduction in sperm parameters and male reproductive hormones.


2015 ◽  
Vol 97 ◽  
Author(s):  
PAOLA A. SPADARO ◽  
HELEN L. NAUG ◽  
EUGENE F. DU TOIT ◽  
DANIEL DONNER ◽  
NATALIE J. COLSON

SummaryConsumption of palatable foods high in refined carbohydrate has been implicated as a contributing factor to the epidemic levels of obesity. Such foods may disrupt appetite regulation in the hypothalamus through alterations in hunger and satiety signalling. This investigation examined whether a palatable high refined carbohydrate (HRC) diet with the potential to induce obesity was linked to modulation of serotonin and dopamine signalling within the hypothalamus of rats. Male Wistar rats were allowed ad libitum access to either a palatable refined carbohydrate enriched (HRC) diet or standard chow (SC). Visceral fat percentage was used as a measure of the animals' weight gain during the trial. Real-time PCR was applied to determine any variation in levels of expression of the serotonin (Slc6A4 or Sert) and dopamine transporter (Slc6A3 or Dat) genes. After 29 weeks, the HRC group showed a significant increase in visceral fat percentage accompanied by increased expression of Sert. Higher levels of circulating triglycerides were also seen. This investigation determined that a refined high carbohydrate diet is associated with visceral obesity, increased circulating lipids in the blood and distorted serotonergic signalling, which possibly alters satiety and hunger signals.


2020 ◽  
Vol 150 (10) ◽  
pp. 2656-2665
Author(s):  
Shingo Hino ◽  
Takayasu Mizushima ◽  
Katsunori Kaneko ◽  
Erika Kawai ◽  
Takashi Kondo ◽  
...  

ABSTRACT Background Intestinal mucins escape digestion and enter the large bowel where they are degraded by the microbiota. To what extent and how mucins impact large-bowel physiology remain unclear. Objective This study examined the large-bowel fermentation characteristics of mucins and mucin-derived O-glycan sugars and whether they affect gut immunity. Methods Mucin secretion from the terminal ileum was determined from feces of ileorectostomized male Wistar rats (age 6 wk) fed an AIN76-based control diet (CD) for 15 d (experiment 1). Normal male Wistar rats (age 6 wk; 4 wk for experiment 4) were fed CD ± porcine stomach mucin (PM) at 6 or 12 g/kg diet, equivalent to 1.5 and 3 times the daily mucin secretion, for 14 d (experiment 2); CD ± N-acetylglucosamine (GlcNAc), fucose, or N-acetylneuraminic acid at 10 g/kg diet for 14 d (experiment 3); or CD ± PM (15 g/kg diet) or GlcNAc (10 g/kg diet) for 29 d (experiment 4). SCFAs, microbial composition, and cecal O-glycan content were assessed. IgA+ plasma cells and regulatory T cells and inflammatory cytokine expression in the cecum were evaluated (experiment 4). Results Daily mucin secretion corresponded to 43.2 μmol of O-glycans. Cecal O-glycan contents were comparable between CD- and PM-fed rats. PM-fed rats harbored more mucin-degrading bacteria. Cecal concentrations of acetate (+37%) and n-butyrate (+73%) were higher in 12-g/kg PM diet–fed rats versus CD (P &lt; 0.05). Among O-glycan sugars, only GlcNAc produced higher n-butyrate concentrations (+68%) versus CD (P &lt; 0.05), with increased numbers of butyrate-producing bacteria. GlcNAc increased the abundance of IgA+ plasma cells (+29%) and regulatory T cells (+33%) versus CD, whereas PM increased IgA+ plasma cells (+25%) (all P &lt; 0.05). GlcNAc and PM decreased expression of Tnfa (−30%, −40%) and Ifng (−30%, −70%) versus CD (all P &lt; 0.05). Conclusions Mucin-derived O-glycans act as endogenous fiber and maintain mucosal immune homeostasis via large-bowel SCFA production in rats.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1563-1563
Author(s):  
Shingo Hino ◽  
Takayasu Mizushima ◽  
Katsunori Kaneko ◽  
Erika Kawai ◽  
Takashi Kondo ◽  
...  

Abstract Objectives Intestinal mucins escape digestion and enter the large bowel where they are degraded by microbiome. To what extent and how mucins impact large-bowel physiology remain unclear. This study examined the large-bowel fermentation characteristics of mucins and mucin-derived O-glycan sugars and whether mucins and N-acetylglucosamine (GlcNAc) affect gut immunity. Methods Mucin secretion from the terminal ileum was determined from feces of ileorectostomized male Wistar rats (age 6 weeks) fed AIN76-based control diet (CD) for 15 d (Expt. 1). Normal male Wistar rats (age 6 weeks; 4 weeks for Expt. 4) were fed CD ± porcine stomach mucin (PM) at 6 or 12g/kg diet, equivalent to 1.5 and 3 times daily mucin secretion, for 14 d (Expt. 2); CD ± GlcNAc, fucose, or N-acetylneuraminic acid at 10g/kg diet for 14 d (Expt. 3); or CD ± PM (15 g/kg diet) or GlcNAc (10 g/kg diet) for 29 d (Expt. 4). Short-chain fatty acids (SCFAs), microbial composition, and cecal O-glycan content were assessed. IgA+ plasma and regulatory T cells and inflammatory cytokine expression in the cecum were evaluated (Expt. 4). Results Daily mucin secretion corresponded to 43.2 mmol of O-glycans. PM was efficiently fermented in the cecum, as evidenced by comparable amounts of cecal O-glycans between groups. PM-fed rats harbored more mucin-degrading bacteria. Cecal SCFA concentrations, particularly n-butyrate, were higher in 12g/kg PM diet-fed rats versus CD (P &lt; 0.05). Among O-glycan sugars, only GlcNAc produced higher n-butyrate concentrations versus CD (P &lt; 0.05), with increased numbers of several butyrate-producing bacteria. GlcNAc increased the abundance of IgA + plasma and regulatory T cells versus CD (P &lt; 0.05). PM produced a similar but less-significant trend. GlcNAc and PM feeding decreased expression of Tnfa and Ifng versus CD (P &lt; 0.05). Conclusions Mucin-derived O-glycans act as endogenous fiber and maintain mucosal immune homeostasis via large-bowel SCFA production in rats. Funding Sources JSPS KAKENHI.


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