Effects of omega fatty acids on the short-term postprandial satiety related peptides in rats

We aimed to assess the effects of omega fatty acids on time depending on responses of satiety hormones. Sixty adult rats were randomly divided into 4 groups; linoleic acid (LA), α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) groups. For each fatty acid, the dose of 400 mg/kg was applied by oral gavage. Blood samples were taken after the 15, 30, 60 and 120 minutes. Ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), leptin and insulin hormones were analyzed by ELISA. We observed the significant increases (p<0.05) of the levels of CCK between n-3 (ALA, at 60th min; EPA, at 30th and 60th min and DHA, at 60 min) and n-6 (LA) supplemented rats. The highest GLP-1 levels were in ALA (0.70 ng/mL) and DHA (0.67 ng/mL) supplemented groups at 60th and 120th min indicating n-3 fatty acids efficiency on satiety compared to LA. It seems that ALA at 60th min and EPA at 120th min could provide the highest satiety effect with the highest insulin response, while the efficiency of LA supplementation on insulin-induced satiety diminished. The only significant change in AUC values among all hormones was in the CCK of the ALA group (p=0.004). The level of leptin increased in DHA and EPA supplemented rats (p=0.140). Our results showed that dietary omega fatty acids influenced the releasing of hormones in different ways possibly depending on chain length or saturation degree. Comprehensive studies need to be addressed for each fatty acid on satiety-related peptide hormones.

Acute oral toxicity of zinc phosphide: an assessment for wild house mice in Australia

BACKGROUND: The efficacy of zinc phosphide (ZnP) for broadacre control of wild house mice in Australia is being reported by growers as increasingly variable. Have mice become less sensitive over time or are they taking a sub-lethal dose and developing aversion? In this laboratory study the sensitivity of groups of wild caught and an outbred laboratory strain of mice was assessed using oral gavage of a range of ZnP concentrations. The willingness of mice to consume ZnP-coated grains was then determined. RESULTS: Each mouse group had very similar LD50 values (72 to 79 mg ZnP per kg body weight) which are significantly higher than previously reported. Time to death post-gavage ranged between 2.5 to 48 h. ZnP coated grains (50 mg ZnP per kg grain) presented in the absence of alternative food were consumed and 94 percent of wild mice died. Mice provided with alternative food and ZnP coated wheat grains (either 25 or 50 mg ZnP per kg grain) consumed toxic and non-toxic grains, and mortality was lower (33 to 55 percent). If a sublethal amount of ZnP coated grain was consumed, aversion occurred mostly in the presence of alternative food. CONCLUSIONS: The sensitivity of wild house mice to ZnP in Australia is significantly lower than previously assumed. Under laboratory conditions ZnP coated grains coated with a new higher dose (50 mg ZnP per kg grain) were readily consumed. Consumption of toxic grain occurred when alternative food was available but was decreased. It is important to assess the efficacy of the higher ZnP dose per grain under natural field conditions, especially when background food is low.

Bismuth Subgallate as a Local Hemostatic Agent

Background: Patients on clopidogrel increased bleeding risk after surgery. This drug prolonged bleeding time, increased bleeding volume and induced secondary bleeding because its active metabolite inhibited platelets aggregation and interfered with haemostatic plug stabilization. Conventional methods, such as pressing sterile gauze on the surgery site, showed less effective to stop bleeding in patients on clopidogrel. This research aims to prove the haemostatic effect of bismuth subgallate both on normal and delayed platelet aggregation due to clopidogrel.Methods: Twenty-eight Wistar rats were equally and randomly administered with clopidogrel (10 mg/kgBW) or NaCl 0.9% (saline) via oral gavage. After anesthetizing, we amputated transversely their tail 10 mm from the distal tip. Bleeding after amputation was controlled with pressing gauze soaked in saline or bismuth subgallate solution. After 60 seconds, bleeding assays (bleeding time, bleeding volume, and secondary bleeding) have been observed, recorded, and analysed both in normal and clopidogrel groups.Results: Clopidogrel groups had significantly longer bleeding time, greater bleeding volume, and had more secondary bleeding rather than saline groups (p <.05). Using bismuth subgallate as local haemostatic agent decreased bleeding time and bleeding volume significantly (p <.05) both in normal and clopidogrel groups. Conclusions: Bismuth subgallate has a haemostatic effect on both clopidogrel and normal rat tail bleeding models.

Effects of Eimeria tenella Infection on Key Parameters for Feed Efficiency in Broiler Chickens

The purpose of the study was to investigate effects of different inoculation dosages of E. tenella on growth performance, gastrointestinal permeability, oocyst shedding, intestinal morphology, fecal consistency, ileal apparent digestibility, antioxidant capacity, and cecal VFA profile in broiler chickens. Five different dosages (T0: 0, T1: 6250, T2: 12,500, T3: 25,000, and T4: 50,000) of E. tenella oocysts were inoculated via oral gavage to fourteen-day-old broilers. Inoculation of E. tenella linearly increased FCR (p < 0.05), and feed intake was quadratically increased on 6 days post-infection (dpi; p = 0.08) and 7 dpi (p = 0.09). Cecal lesion score of each treatment was T0: 0; T1: 0.39 ± 0.14; T2: 0.93 ± 0.21; T3: 1.25 ± 0.16; and T4: 1.58 ± 0.2. Cecal total VFA production was linearly reduced due to E. tenella infection on 6 dpi (p < 0.01). E. tenella infection deepened cecal crypts depth on 6 dpi (CD; p < 0.05). Gastrointestinal permeability tended to be linearly increased (p = 0.07). E. tenella infection tended to linearly reduce duodenal VH (p = 0.1) and jejunal VH on 9 dpi (p = 0.09). Different dosages of E. tenella modulated the tendency of fecal moisture content and oocyst shedding. Therefore, E. tenella infection impaired feed efficiency and small intestinal health mainly by reducing cecal VFA production and deepening cecal CD in broilers.

Evaluation of the Effects of Chitosan on Methotrexate-Induced Oral Mucositis in Rats

I. Background: Methotrexate (MTX), a chemotherapeutic agent, is known to cause oral mucositis. Chitosan has been shown to have a protective effect in inflammatory animal models. This research aimed to examine the protective effect of chitosan against oral mucositis caused by MTX. II. Methods and Results: Wistar albino rats were randomly divided into three groups, 8 in each group as follow: Control (saline via oral gavage for 5 days), MTX (60 mg/kg single dose MTX intraperitoneally on 1st day and for following 4 days saline via oral gavage), and MTX+Chitosan(1st day single dose 60 mg/kg MTX intraperitoneally and followed with 200 mg/kg Chitosan via oral gavage for 4 days). After 24 hours of the last dose, animals were euthanised. Blood, tongue, buccal and palatal mucosa tissues were collected. Serum interleukin 1-beta (IL1-β), tumour necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP-1, and MMP-2) activities, and tissue bcl-2/bax ratio and the expression of caspase-3 (casp-3), and casp-9 were detected. The tissues were also examined histologically. Serum TNF-α, IL1-β, MMP-1 and MMP-2 activities and tissue casp-3 and casp-9 activities significantly increased but the bcl-2/bax ratio significantly decreased in the MTX group compared to the control group. Histologically, diffuse inflammatory cells were observed in MTX group. However, In the MTX + Chitosan group, all parameters approached the values of control group. III. Conclusion: Chitosan has been found to have a protective effect against oral mucosal damage caused by MTX. Thus, it may be a candidate agent against MTX induced oral mucositis.

Reduced Body Fat and Epididymal Adipose Apelin Expression Associated With Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Weight Gain Prevention in High-Fat-Diet Fed Mice

Raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] is a natural aromatic compound found in raspberries and other fruits. Raspberry ketone (RK) is synthetically produced for use as a commercial flavoring agent. In the United States and other markets, it is sold as a dietary supplement for weight control. The potential of RK to reduce or prevent excessive weight gain is unclear and could be a convergence of several different actions. This study sought to determine whether acute RK can immediately delay carbohydrate hyperglycemia and reduce gastrointestinal emptying. In addition, we explored the metabolic signature of chronic RK to prevent or remedy the metabolic effects of diet-induced weight gain. In high-fat diet (HFD; 45% fat)-fed male mice, acute oral gavage of RK (200 mg/kg) reduced hyperglycemia from oral sucrose load (4 g/kg) at 15 min. In HFD-fed female mice, acute oral RK resulted in an increase in blood glucose at 30 min. Chronic daily oral gavage of RK (200 mg/kg) commencing with HFD access (HFD_RK) for 11 weeks resulted in less body weight gain and reduced fat mass compared with vehicle treated (HFD_Veh) and chronic RK starting 4 weeks after HFD access (HFD_RKw4) groups. Compared with a control group fed a low-fat diet (LFD; 10% fat) and dosed with vehicle (LFD_Veh), glucose AUC of an oral glucose tolerance test was increased with HFD_Veh, but not in HFD_RK or HFD_RKw4. Apelin (Apln) gene expression in epididymal white adipose tissue was increased in HFD_Veh, but reduced to LFD_Veh levels in the HFD_RK group. Peroxisome proliferator activated receptor alpha (Ppara) gene expression was increased in the hepatic tissue of HFD_RK and HFD_RKw4 groups. Overall, our findings suggest that long term daily use of RK prevents diet-induced weight gain, normalizes high-fat diet-induced adipose Apln, and increases hepatic Ppara expression.

Effects of larazotide acetate, a tight junction regulator, on the liver and intestinal damage in acute liver failure in rats

Background and Aim The epithelial cells are the strongest determinants of the physical intestinal barrier. Tight junctions (TJs) hold the epithelial cells together and allow for selective paracellular permeability. Larazotide acetate (LA) is a synthetic octapeptide that reduces TJ permeability by blocking zonulin receptors. In this study, we aimed to investigate the effects of LA, a TJ regulator, on the liver and intestinal histology in the model of acute liver failure (ALF) in rats. Materials and Methods The thioacetamide (TAA) group received intraperitoneal (ip) injections of 300 mg/kg TAA for 3 days. The TAA+LA(dw) (drinking water) group received prophylactic 0.01 mg/mL LA orally for 7 days before the first dose of TAA. The LA(dw) group received 0.01 mg/mL LA orally. The TAA + LA(g) (gavage) group received prophylactic 0.01 mg/mL LA via oral gavage for 7 days before the first dose of TAA. The LA(g) group received 0.01 mg/mL LA via oral gavage. While liver tissue was evaluated only with light microscopy, intestinal samples were examined with light and electron microscopy. Results Serum ammonia, AST, and ALT levels in the TAA group were significantly higher than in control groups (all p < 0.01). Serum ALT levels in the TAA + LA(dw) group were significantly lower than in the TAA group ( p < 0.05). However, serum ammonia and ALT levels did not differ between the TAA and other groups. Serious liver damage in the TAA group was accompanied by marked intestinal damage. There was no significant difference between the TAA and TAA + LA(dw) groups and TAA and TAA + LA(g) groups for liver damage scores. However, intestinal damage scores significantly decreased in the TAA + LA(dw) group compared to the TAA group. In the TAA + LA(dw) group, fusion occurred between the surface epithelial cells of neighboring villi and connecting regions formed as epithelial bridges between the villi. Conclusion Our findings suggest that LA reduced intestinal damage by acting on TJs in the TAA-induced ALF model in rats.

E.coli JM83 Damages Mucosal Barrier Inducing Hirschsprung-Associated Enterocolitis via Activated TLR4 / NF-κB / P-p38 Signaling

Purpose Hirschsprung-associated enterocolitis (HAEC) is characterized by intestinal mucosal damage and unbalance of intestinal microbiota. Recent studies have shown that the TLR4/NF-κB/p-p38 signaling in the intestine is of great importance to intestinal mucosal integrity. This study aimed to investigate the role of TLR4/NF-κB/p-p38 signaling in the pathogenesis of HAEC in Escherichia coli (E. coli) JM83 infected Endothelin receptor B (Ednrb)−/− mice. Methods Ednrb −/− mice were administered with E. coli JM83 by oral gavage to establish the HAEC model, mice were randomly divided into WT group, Ednrb−/− group and Ednrb−/−+ E. coli JM83 group. The role of TLR4/NF-κB/p-p38 signaling was evaluated by vivo study. Results The activation of the TLR4/NF-κB/p-p38 signaling induced by E. coli JM83 caused HAEC in Ednrb−/− mice, which was evidenced by a significantly increased expression of TNF-α, TGF-β and IL-10, decreased density of F-actin protein. While TLR4 knockdown improved the degree of enterocolitis and attenuated the expression of IL-10, TNF-α, TGF-β and increased the density of F-actin protein in Ednrb−/− mice after E. coli infection. Conclusions These results indicate that E. coli JM83 activates TLR4/NF-κB/p-p38 signaling to promote the development of HAEC. However, inhibition of this signaling may be benefit to the treatment and prevention of HAEC.

DDRE-26. INHIBITION OF PRMT5 SENSITIZES GLIOBLASTOMA MODELS TO TRAMETINIB TREATMENT

With limited effective therapeutic strategies, the prognosis for glioblastoma (GBM) is very poor. Our previous study shows that the expression of Protein Arginine Methyltransferase 5 (PRMT5) is upregulated in GBM; its inhibition promotes apoptosis and senescence in differentiated and stem-like tumor cells, respectively. MEK inhibitors, including trametinib, are currently under investigation for GBM therapy. In this study, we tested whether inhibition of PRMT5 can enhance the anti-GBM efficacy of trametinib. Patient-derived primary GBM neurospheres (GBMNS) with transient PRMT5 knockdown were treated with trametinib and cell viability, proliferation, cell cycle progression, ELISA, and western blot analysis were conducted. In vivo, PRMT5-intact and -depleted GBMNS were intracranially implanted in NSG mice and treated with trametinib by daily oral gavage, and tumor progression and mice survival rate were analyzed by MRI and Kaplan-Meier survival curve, respectively. Depletion of PRMT5 increased the cytotoxic effect of trametinib in GBMNS. Trametinib treatment increased the activity of ERBB3 and AKT; With PRMT5 knockdown, the activity of both AKT and ERBB3 decreased significantly. But, inhibition of ERBB3 alone failed to block the trametinib-induced AKT activity suggesting that even though PRMT5 regulates the activity of both ERBB3 and AKT, the enhanced antitumor effect imparted by PRMT5 knockdown in trametinib treated GBMNS is because of AKT inhibition alone. In vivo, PRMT5-depletion extended the survival of the tumor-bearing mice that further increased in combination with trametinib treatment. Interestingly, trametinib treatment alone had no survival benefit.