Desvenlafaxine succinate ameliorates visceral hypersensitivity but delays solid gastric emptying in rats

2013 ◽  
Vol 305 (4) ◽  
pp. G333-G339 ◽  
Author(s):  
Fei Dai ◽  
Yong Lei ◽  
Shiying Li ◽  
Gengqing Song ◽  
Jiande D. Z. Chen
Keyword(s):  
Acetic Acid ◽  
Gastric Emptying ◽  
Rodent Model ◽  
Visceral Hypersensitivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Visceral Sensitivity ◽  
Gastric Distention ◽  
Way 100635 ◽  
Norepinephrine Reuptake Inhibitor ◽  
Norepinephrine Reuptake

Desvenlafaxine succinate (DVS) is a novel serotonin and norepinephrine reuptake inhibitor. The aim of this study was to investigate the effects of DVS on visceral hypersensitivity and solid gastric emptying in a rodent model of gastric hyperalgesia. Twenty-eight gastric hyperalgesia rats and 20 control rats were used. Visceral sensitivity during gastric distention (GD) was assessed by recording of electromyogram (EMG) at pressures of 20, 40, 60, and 80 mmHg. DVS with doses of 1, 10, and 30 mg/kg were administrated by gavage, 5-HT1A antagonist (WAY-100635, 0.3 mg/kg) was given subcutaneously, and 5-HT2A antagonist (ketanserin, 1 mg/kg) was given intraperitoneally. The level of norepinephrine in plasma was measured by enzyme-linked immunosorbent assay. We found that 1) visceral hypersensitivity induced by acetic acid was validated. 2) DVS dose-dependently reduced visceral hypersensitivity in the gastric hypersensitivity rats. The EMG (% of baseline value without GD) during GD at 60 and 80 mmHg with DVS at a dose of 30 mg/kg were 119.4 ± 2.3% (vs. saline 150.9 ± 2.7%, P < 0.001) and 128.2 ± 3.2% (vs. saline 171.1 ± 2.4%, P < 0.001). Similar findings were observed at a dose of 10 mg/kg. DVS at a dose of 1 mg/kg reduced visceral hypersensitivity only during GD at 60 mmHg. 3) Neither WAY-100635 nor ketanserin blocked the effect of DVS on visceral sensitivity. 4) DVS at 30 mg/kg significantly increased plasma NE level ( P = 0.012 vs. saline). 5) DVS at 30 mg/kg significantly delayed solid gastric emptying ( P < 0.05 vs. saline). We conclude that DVS reduces visceral sensitivity in a rodent model of visceral hypersensitivity and delays solid gastric emptying. Caution should be made when DVS is used for treating patients.

scholarly journals Sini-San Regulates the NO-cGMP-PKG Pathway in the Spinal Dorsal Horn in a Modified Rat Model of Functional Dyspepsia

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Zhenyu Wu ◽  
Xiaofang Lu ◽  
Shengsheng Zhang ◽  
Chunyang Zhu
Keyword(s):  
Gene Expression ◽  
Dorsal Horn ◽  
Functional Dyspepsia ◽  
Rat Model ◽  
Spinal Dorsal Horn ◽  
Visceral Hypersensitivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Gastric Distention ◽  
Real Time Quantitative Pcr ◽  
Spinal Dorsal

The present study investigated the effect of Chinese medicine Sini-San (SNS) on visceral hypersensitivity in a rat model of functional dyspepsia (FD), and it explored related underlying mechanisms. The rat model of FD was developed by combining neonatal iodoacetamide (IA) treatment and adult tail-clamping. After SNS treatment, the behavior and electromyographic testing were performed to evaluate the visceromotor responses of rats to gastric distention. Immunofluorescence was used to detect the distribution of iNOS-positive cells in the spinal dorsal horn, while the real-time quantitative PCR and western blot were used for detection of the gene expression of c-fos, iNOS, and GABAb and protein levels of iNOS and GABAb in the spinal dorsal horn, respectively. The protein concentration of cGMP and PKG proteins in the spinal dorsal horn were quantified by enzyme-linked immunosorbent assay. In this study, SNS treatment significantly reduced the behavioral score and electromyographic response to graded intragastric distension pressure. The middle-dose of SNS treatment significantly reduced the distribution of iNOS-positive cells in the spinal dorsal horn of FD model rats. The gene expression of c-fos, iNOS, and GABAb and the protein contents of iNOS, GABAb, cGMP, and PKG in the spinal dorsal horn of FD model rats were restored to a normal level by middle-dose of SNS treatment. Our results suggest that Sini-San may alleviate the visceral hypersensitivity in FD model rats via regulation of the NO/cGMP/PKG pathway in the spinal dorsal horn.

scholarly journals Inhibition of bladder overactivity by duloxetine in combination with foot stimulation or WAY-100635 treatment in cats

2013 ◽  
Vol 305 (12) ◽  
pp. F1663-F1668 ◽  
Author(s):  
Zeyad Schwen ◽  
Yosuke Matsuta ◽  
Bing Shen ◽  
Jicheng Wang ◽  
James R. Roppolo ◽  
...  
Keyword(s):  
Combined Treatment ◽  
Bladder Capacity ◽  
Saline Control ◽  
Threshold Intensity ◽  
Novel Treatment ◽  
Way 100635 ◽  
Norepinephrine Reuptake Inhibitor ◽  
The Right ◽  
Norepinephrine Reuptake ◽  
Bladder Inhibition

The purpose of this study was to determine whether duloxetine [a serotonin (5-HT)-norepinephrine reuptake inhibitor] combined with transcutaneous foot stimulation or WAY-100635 (a 5-HT1A antagonist) can enhance inhibition of bladder overactivity in cats. Cystometrograms were performed on eight cats under α-chloralose anesthesia by infusing saline and then 0.25% acetic acid (AA) to induce bladder overactivity. To inhibit bladder overactivity, foot stimulation (5 Hz) was applied via transcutaneous pad electrodes to the right hindfoot at two and four times the threshold intensity for inducing a toe twitch. Duloxetine (0.003–3 mg/kg) was administered intravenously to determine the effect of combination treatment. After the 3 mg/kg dose of duloxetine, WAY-100635 (0.5 mg/kg) was given intravenously. AA irritation significantly ( P < 0.0001) reduced bladder capacity to 42.7 ± 7.4% of the saline control capacity. Foot stimulation alone at both two and four times the threshold intensity significantly ( P < 0.0001) inhibited bladder overactivity and increased bladder capacity to 66.7 ± 6.3% and 85.7 ± 6.5% of the saline control, respectively. Duloxetine alone dose dependently inhibited bladder overactivity and completely restored bladder capacity to the saline control (109 ± 15.5%) at 3 mg/kg. Although duloxetine combined with foot stimulation did not further enhance inhibition, WAY-100635 (0.5 mg/kg) given after 3 mg/kg duloxetine further increased ( P = 0.008) bladder capacity to 162.2 ± 22.5% of the saline control. Although duloxetine and foot stimulation independently inhibited bladder overactivity, combined treatment did not enhance inhibition. Duloxetine combined with WAY-100635, however, synergistically enhanced bladder inhibition, indicating a potential novel treatment for overactive bladder if duloxetine is combined with a 5-HT1A receptor antagonist drug.

scholarly journals 325 INSULIN-LIKE GROWTH FACTOR-I CONCENTRATIONS IN OVIDUCT FLUID OF SUPEROVULATED EWES DURING THE PERI-OVULAR PERIOD

2005 ◽  
Vol 17 (2) ◽  
pp. 313
Author(s):  
M.A. Kakar ◽  
S. Maddocks ◽  
M.F. Lorimer ◽  
D.O. Kleemann ◽  
S.K. Walker
Keyword(s):  
Acetic Acid ◽  
Liquid Chromatography ◽  
Growth Factor ◽  
High Performance ◽  
Enzyme Linked Immunosorbent Assay ◽  
Research Station ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Oviduct Fluid ◽  
Oviductal Fluid

This study examined the concentrations of insulin-like growth factor-1 (IGF-1) in oviduct fluid during the peri-ovular period as a reference for the establishment of optimal in vitro culture conditions for sheep embryos. Six mature ewes (4–5 years, 58–67 kg) of comparable body condition were fed a standard diet for two weeks before the start of fluid collection. Ewes were superovulated using conventional treatment involving a progestagen, FSH, and GnRH treatment. Oviducts were catheterized four days (which is sufficient time to recover from surgery) before collection of oviductal fluid, which started one day (Day 1) before the time of ovulation (Day 0) and continued until five days later (Day 5). Oviductal fluid was acidified by diluting into 0.8 M acetic acid/0.2 M trimethylamine, pH 2.8, mixed, and incubated to dissociate IGFs from IGF-binding proteins (IGFBPs). Following incubation, acidified fluid was centrifuged at 10,000g through a 0.1-mm Micro-spin centrifuge filter; the filtrate transferred to glass high-performance liquid chromatography (HPLC) vials. IGFs and IGFBPs were separated from one another by high-performance size-exclusion liquid chromatography using a Protein-Pak 125 column (Waters Corporation, Milford, MA, USA) and 0.2 M acetic acid, 0.05 M trimethylamine, pH 2.8, at a flow rate of 1 mL/min. Oviductal fluid IGF-I was collected in a single 2-mL fraction directly from the HPLC and its concentration measured by an IGF-I-specific enzyme-linked immunosorbent assay (Diagnostic Systems Laboratories, Inc. Webster, TX, USA). The data were analyzed by analysis of variance. The non-superovulation group had significantly higher concentrations of oviductal IGF-I compared with the superovulation group. In the superovulated group, there was, however, a significant effect of day on the oviductal fluid IGF-I concentration (P < 0.01) such that the concentrations of IGF-I first increased for three days and then decreased for the remaining four days. In the non-superovulation group, there was no significant two-way interaction between ovulation and day. It can be concluded that the levels of IGF-I increase over time and then decrease. Authors express thanks to the help of Jenn Skye and Hemish Turretfield Research Station SA.

scholarly journals Dynamic Evaluation of Compound Ento-PB for the Repair of Mucosal Ulcer in Dogs With Acetic Acid-induced Experimental Colitis 

2020 ◽  
Author(s):  
Jin-hu Chen ◽  
Jian-ting Zhao ◽  
Zheng-yong Yu ◽  
Yi-hao Che ◽  
Yu-jia Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Acetic Acid ◽  
Inflammatory Cytokines ◽  
Mucosal Healing ◽  
Dynamic Monitoring ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Expression Levels ◽  
Cox 2 ◽  
Anti Inflammatory

Abstract Background: Mucosal inflammation and ulcer play important roles in the pathogenesis of ulcerative colitis. As as traditional Chinese medicine compound composed of Periplaneta americana and Taraxacum mongolicum, Ento-PB is always prescribed for the treatment of ulcer and inflammatory diseases. As for the significant role of P. americana in terms of promoting mucosal healing, the compatibility of the anti-inflammatory drug T. mongolicum may enable Ento-PB to simultaneously play anti-inflammatory and promote mucosal healing effects on the treatment of UC. Therefore, this study aimed to evaluate the therapeutic potential and possible mechanism of Ento-PB for UC by establishing an acetic acid-induced colitis model in dogs.Methods: Preliminary identification to the chemical components of compound Ento-PB was carried out through high performance liquid chromatography. A cross-bred dogs model of acetic acid-induced ulcerative colitis was established to evaluate the efficacy of compound Ento-PB. The expression levels of inflammatory cytokines C-reactive protein (CRP), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in plasma were measured by carrying out enzyme-linked immunosorbent assay (ELISA).Results: With the extension of treatment time, Ento-PB could effectively improve clinical symptoms of UC cross-bred dogs. Colonoscopy displayed that mucosal redness, swelling and congestion decreased gradually, and obviously repaired after mucosal injury. The intestinal texture was gradually clear, and the colonoscopy score gradually reduced. Histopathological examination revealed that the structure of colon was restored significantly, the infiltration of inflammatory cells was reduced, and the histological score was remarkably reduced. At the same time, the results of dynamic monitoring of inflammatory cytokines in plasma proved that Ento-PB can gradually down-regulate the activity of CRP, iNOS and COX-2, reduce the expression levels of inflammatory cytokines TNF-α and IL-1β, and gradually restore anti-inflammatory and the expression level of cytokine IL-10.Conclusions: Ento-PB reduces the level of pro-inflammatory cytokines in a dose- and time-dependent manner and inflammation, improves colon tissue lesions and the repair of intestinal mucosa after injury, and effectively increases acetic acid-induced colon inflammation in UC cross-bred dogs.

Sign in / Sign up

Export Citation Format

Share Document