The gastroprotective effect of obestatin on indomethacin-induced acute ulcer is mediated by a vagovagal mechanism

AbstractIn order to investigate the role of the vagus nerve in the possible gastroprotective effect of obestatin on the indomethacin-induced acute oxidative gastric injury, Sprague-Dawley rats of both sexes were injected subcutaneously with indomethacin (25 mg/kg, 5% NaHCO3) followed by obestatin (10, 30 or 100 μg/kg). In other sets of rats, surgical vagotomy (Vx) or selective degeneration of vagal afferent fibers by perivagal capsaicin was performed before the injections of indomethacin or indomethacin + obestatin (30 μg/kg). Gastric serosal blood flow was measured, and 4 h after ulcer induction gastric tissue samples were taken for histological and biochemical assays. Obestatin reduced the severity of indomethacin-induced acute ulcer via the reversal of reactive hyperemia, by inhibiting ulcer-induced neutrophil infiltration and lipid peroxidation along with the replenishment of glutathione (GSH) stores, whereas Vx abolished the inhibitory effect of obestatin on blood flow and lipid peroxidation, and worsened the severity of ulcer. On the other hand, serosal blood flow was even amplified by the selective denervation of the capsaicin-sensitive vagal afferent fibers, but obestatin-induced reduction in ulcer severity was not altered. In conclusion, the gastroprotective effect of obestatin on indomethacin-induced ulcer appears to involve the activation of the vagovagal pathway.

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Endogenous CCK disrupts the MMC pattern via capsaicin-sensitive vagal afferent fibers in the rat

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1997.272.1.g100 ◽

1997 ◽

Vol 272 (1) ◽

pp. G100-G105 ◽

Cited By ~ 5

Author(s):

A. Rodriguez-Membrilla ◽

P. Vergara

Keyword(s):

Intravenous Infusion ◽

Sprague Dawley ◽

Rat Intestine ◽

Intracerebroventricular Infusion ◽

C Fibers ◽

Afferent Fibers ◽

Sprague Dawley Rats ◽

Vagal Afferent ◽

Endogenous Release ◽

Stimulation Of

A meal disrupts migrating motor complexes (MMC) in the rat intestine through stimulation of peripheral cholecystokinin (CCK)-B and central CCK-A receptors. The aim of this study was to determine pathways implicated in postprandial disruption of the MMC mediated by CCK. Sprague-Dawley rats were prepared with electrodes for electromyography in the small intestine, and ablation of vagal afferent C-fibers by capsaicin was carried out. Endogenous release of CCK was induced by oral administration of soybean trypsin inhibitor (SBTI). In control rats SBTI disrupted MMC and generated an irregular spiking activity that lasted longer than 3 h. Intravenous infusion of L-365,260 (2 x 10(-7) mol/kg) but not of L-364,718 (3 x 10(-9) mol/kg) restored the MMC pattern. In capsaicin-treated rats, SBTI did not modify fasting activity. Infusion of CCK octapeptide (CCK-8) at 3 x 10(-9) mol.kg-1.h-1 disrupted the MMC, although the response was quantitatively and qualitatively different from SBTI. The effect was reversed by intravenous infusion of L-364,718 or L-365,260 and intracerebroventricular infusion of L-364,718. In capsaicin-treated rats, the intracerebroventricular or intravenous infusion of L-364,718 inhibited CCK-8 effects. However, the intravenous infusion of L-365,260 did not reverse the MMC pattern. These results suggest that the disruption of the MMC mediated by CCK is due to stimulation of peripheral CCK-B receptors located in vagal afferent fibers. This initiates a reflex including stimulation of central CCK-A receptors. Exogenous CCK also stimulates peripheral CCK-A receptors not located in capsaicin-sensitive vagal afferent fibers.

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The Gastroprotective Effect of Small Molecule Oligopeptides Isolated from Walnut (Juglans regia L.) against Ethanol-Induced Gastric Mucosal Injury in Rats

Nutrients ◽

10.3390/nu12041138 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1138 ◽

Cited By ~ 2

Author(s):

Rui Liu ◽

Yun-Tao Hao ◽

Na Zhu ◽

Xin-Ran Liu ◽

Jia-Wei Kang ◽

...

Keyword(s):

Body Weight ◽

Gastric Content ◽

Juglans Regia ◽

Antioxidant Properties ◽

Mucosal Injury ◽

Gastric Mucosal Injury ◽

Gastric Injury ◽

Protective Effects ◽

Sprague Dawley ◽

Gastroprotective Effect

The study investigated the protective effect of walnut oligopeptides (WOPs) against ethanol-induced gastric injury using Sprague-Dawley (SD) rats. Rats were randomly divided into seven groups based on body weight (10/group), normal group, ethanol group, whey protein group (220 mg/kg body weight), omeprazole group (20 mg/kg body weight), and three WOPs groups (220, 440, 880 mg/kg body weight). After 30 days of treatment with WOPs, rats were given 5 mL/kg absolute ethanol by gavage to induce gastric mucosal injury. Gastric ulcer index (GUI) were determined and the following measured; gastric content pH, gastric mucin, endogenous pepsinogens (PG), prostaglandin E2 (PGE2), inflammatory cytokines, oxidative stress indicators, and the expression of apoptosis-related proteins were measured to evaluate the gastroprotective effect of WOPs. The results showed that the administration with WOPs markedly mitigated the hemorrhagic gastric lesions caused by ethanol in rats, and decreased the GUI, the gastric content pH, PG1, PG2, and NO levels, enhanced mucin and PGE2. Also, WOPs repressed gastric inflammation through the reduction of TNF-α, IL-6, IL-1β and increase IL-10 levels, and revealed antioxidant properties with the enhancement of superoxide dismutase, glutathione, and catalase activity, while reduction of malondialdehyde. Moreover, WOPs treatment significantly down-regulated Bax, caspase-3 and nuclear factor-κB p65 (NF-κB p65) expression, while up-regulating the expression of Bcl-2 and inhibitor kappa Bα (IκBα) protein. These results indicated that WOPs have protective effects against ethanol-induced gastric mucosal injury in rats through anti-inflammatory, anti-oxidation, and anti-apoptosis mechanisms.

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Ventilatory threshold is related to walking tolerance in patients with intermittent claudication

VASA ◽

10.1024/0301-1526/a000203 ◽

2012 ◽

Vol 41 (4) ◽

pp. 275-281 ◽

Cited By ~ 3

Author(s):

da Rocha Chehuen ◽

G. Cucato ◽

P. dos Anjos Souza Barbosa ◽

A. R. Costa ◽

M. Ritti-Dias ◽

...

Keyword(s):

Blood Flow ◽

Oxygen Uptake ◽

Intermittent Claudication ◽

Lower Limb ◽

Ventilatory Threshold ◽

Reactive Hyperemia ◽

Ankle Brachial Index ◽

Metabolic Parameters ◽

Walking Distance ◽

The Relationship

Background: This study assessed the relationship between lower limb hemodynamics and metabolic parameters with walking tolerance in patients with intermittent claudication (IC). Patients and methods: Resting ankle-brachial index (ABI), baseline blood flow (BF), BF response to reactive hyperemia (BFRH), oxygen uptake (VO2), initial claudication distance (ICD) and total walking distance (TWD) were measured in 28 IC patients. Pearson and Spearman correlations were calculated. Results: ABI, baseline BF and BF response to RH did not correlate with ICD or TWD. VO2 at first ventilatory threshold and VO2peak were significantly and positively correlated with ICD (r = 0.41 and 0.54, respectively) and TWD (r = 0.65 and 0.71, respectively). Conclusions: VO2peak and VO2 at first ventilatory threshold, but not ABI, baseline BF and BFHR were associated with walking tolerance in IC patients. These results suggest that VO2 at first ventilatory threshold may be useful to evaluate walking tolerance and improvements in IC patients.

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Tanshinone IIA attenuates elastase-induced AAA in rats via inhibition of MyD88-dependent TLR-4 signaling

VASA ◽

10.1024/0301-1526/a000326 ◽

2014 ◽

Vol 43 (1) ◽

pp. 39-46 ◽

Cited By ~ 16

Author(s):

Tao Shang ◽

Feng Ran ◽

Qian Qiao ◽

Zhao Liu ◽

Chang-Jian Liu

Keyword(s):

Nuclear Factor Κb ◽

Tanshinone Iia ◽

Myeloid Differentiation ◽

Aortic Tissue ◽

Toll Like Receptor ◽

Sprague Dawley ◽

Toll Like Receptor 4 ◽

Tissue Samples ◽

Myeloid Differentiation Factor ◽

And Control

Background: The purpose of this study was to determine whether myeloid differentiation factor88-dependent Toll-Like Receptor-4 (TLR-4) signaling contributed to the inhibition of abdominal aortic aneurysm (AAA) by Tanshinone IIA (Tan IIA). Materials and methods: Male Sprague-Dawley rats (n = 12 / group) were randomly distributed into three groups: Tan IIA, control, and sham. The rats from Tan IIA and control groups under-went intra-aortic elastase perfusion to induce AAAs, and those in the sham group were perfused with saline. Only the Tan IIA group received Tan IIA (2 mg / rat / d). Aortic tissue samples were harvested at 24 d after perfusion and evaluated using reverse transcriptase-polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence. Results: The over-expression of Toll-Like Receptor-4 (TLR-4), Myeloid Differentiation factor 88 (MyD88), Phosphorylated Nuclear Factor κB (pNF-κB) and Phosphorylated IκBα (pIκBα) induced by elastase perfusion were significantly decreased by Tan IIA treatment. Conclusions: Tan IIA attenuates elastase-induced AAA in rats possibly via the inhibition of MyD88-dependent TLR-4 signaling, which may be one potential explanation of why Tan IIA inhibits AAA development through multiple effects.

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Blood flow and high-energy phosphates in microregions of left ventricular subendocardium

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1981.240.5.h804 ◽

1981 ◽

Vol 240 (5) ◽

pp. H804-H810 ◽

Cited By ~ 1

Author(s):

H. D. Kleinert ◽

H. R. Weiss

Keyword(s):

Blood Flow ◽

Linear Relationship ◽

Tissue Perfusion ◽

High Energy ◽

Left Ventricular ◽

Significant Loss ◽

Tissue Blood Flow ◽

High Energy Phosphates ◽

Tissue Samples ◽

Heterogeneous Distribution

Blood flow and high-energy phosphate (HEP) content were determined simultaneously in multiple microregions of left ventricular subendocardium in 29 normal anesthetized open-chest rabbits by use of a new micromethod to determine whether a direct linear relationship existed between these parameters. Tissue samples weighed 1-2 mg. ATP and creatine phosphate (CP) content were quantitated in quick-frozen hearts by fluorometry at sites where tissue perfusion was measured by H2 clearance by use of bare-tipped platinum electrodes. A series of validation studies were conducted to ensure that 1) no significant damage to the tissue surrounding the electrode occurred during the period of experimentation and 2) no significant loss of biochemical constituents had occurred due to labile processes during freezing or storage of the tissue. Blood flow, ATP, and CP values averaged 79.1 +/- 24.1 (SD) ml.min-1.100 g-1, 4.9 +/- 1.3 mumol/g tissue, and 8.0 +/- 3.0 mumol/g tissue, respectively, and are similar to those reported in studies using larger tissue samples. Correlation between the heterogeneous distribution of tissue perfusion and HEP revealed no direct linear relationship between these parameters in the normal unstressed rabbit subendocardium.

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Novel Hydrogen Sulfide (H2S)-Releasing BW-HS-101 and Its Non-H2S Releasing Derivative in Modulation of Microscopic and Molecular Parameters of Gastric Mucosal Barrier

International Journal of Molecular Sciences ◽

10.3390/ijms22105211 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5211

Author(s):

Dominik Bakalarz ◽

Edyta Korbut ◽

Zhengnan Yuan ◽

Bingchen Yu ◽

Dagmara Wójcik ◽

...

Keyword(s):

Blood Flow ◽

Hydrogen Sulfide ◽

Gastric Mucosa ◽

Dna Oxidation ◽

Gastric Blood Flow ◽

Gastric Mucosal Damage ◽

Mucosal Barrier ◽

Gastric Injury ◽

Zinc Protoporphyrin ◽

Anti Inflammatory

Hydrogen sulfide (H2S) is an endogenously produced molecule with anti-inflammatory and cytoprotective properties. We aimed to investigate for the first time if a novel, esterase-sensitive H2S-prodrug, BW-HS-101 with the ability to release H2S in a controllable manner, prevents gastric mucosa against acetylsalicylic acid-induced gastropathy on microscopic and molecular levels. Wistar rats were pretreated intragastrically with vehicle, BW-HS-101 (0.5–50 μmol/kg) or its analogue without the ability to release H2S, BW-iHS-101 prior to ASA administration (125 mg/kg, intragastrically). BW-HS-101 was administered alone or in combination with nitroarginine (L-NNA, 20 mg/kg, intraperitoneally) or zinc protoporphyrin IX (10 mg/kg, intraperitoneally). Gastroprotective effects of BW-HS-101 were additionally evaluated against necrotic damage induced by intragastrical administration of 75% ethanol. Gastric mucosal damage was assessed microscopically, and gastric blood flow was determined by laser flowmetry. Gastric mucosal DNA oxidation and PGE2 concentration were assessed by ELISA. Serum and/or gastric protein concentrations of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, VEGF, GM-CSF, IFN-γ, TNF-α, and EGF were determined by a microbeads/fluorescent-based multiplex assay. Changes in gastric mucosal iNOS, HMOX-1, SOCS3, IL1-R1, IL1-R2, TNF-R2, COX-1, and COX-2 mRNA were assessed by real-time PCR. BW-HS-101 or BW-iHS-101 applied at a dose of 50 μmol/kg protected gastric mucosa against ASA-induced gastric damage and prevented a decrease in the gastric blood flow level. H2S prodrug decreased DNA oxidation, systemic and gastric mucosal inflammation with accompanied upregulation of SOCS3, and EGF and HMOX-1 expression. Pharmacological inhibition of nitric oxide (NO) synthase but not carbon monoxide (CO)/heme oxygenase (HMOX) activity by L-NNA or ZnPP, respectively, reversed the gastroprotective effect of BW-HS-101. BW-HS-101 also protected against ethanol-induced gastric injury formation. We conclude that BW-HS-101, due to its ability to release H2S in a controllable manner, prevents gastric mucosa against drugs-induced gastropathy, inflammation and DNA oxidation, and upregulate gastric microcirculation. Gastroprotective effects of this H2S prodrug involves endogenous NO but not CO activity and could be mediated by cytoprotective and anti-inflammatory SOCS3 and EGF pathways.

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Using reactive hyperemia to investigate the effect of cupping sizes of cupping therapy on skin blood flow responses

Journal of Back and Musculoskeletal Rehabilitation ◽

10.3233/bmr-200120 ◽

2021 ◽

pp. 1-7

Author(s):

Xiangfeng He ◽

Xueyan Zhang ◽

Fuyuan Liao ◽

Li He ◽

Xin Xu ◽

...

Keyword(s):

Blood Flow ◽

Laser Doppler Flowmetry ◽

Skin Blood Flow ◽

Repeated Measures ◽

Recovery Time ◽

Reactive Hyperemia ◽

Cupping Therapy ◽

Doppler Flowmetry ◽

Healthy Participants ◽

Hyperemic Response

BACKGROUND: Various cupping sizes of cupping therapy have been used in managing musculoskeletal conditions; however, the effect of cupping sizes on skin blood flow (SBF) responses is largely unknown. OBJECTIVE: The objective of this study was to compare the effect of three cupping sizes of cupping therapy on SBF responses. METHODS: Laser Doppler flowmetry (LDF) was used to measure SBF on the triceps in 12 healthy participants in this repeated measures study. Three cup sizes (35, 40 and 45 mm in diameter) were blinded to the participants and were tested at -300 mmHg for 5 minutes. Reactive hyperemic response to cupping therapy was expressed as a ratio of baseline SBF. RESULTS: All three sizes of cupping cups resulted in a significant increase in peak SBF (p< 0.001). Peak SBF of the 45 mm cup (9.41 ± 1.32 times) was significantly higher than the 35 mm cup (5.62 ± 1.42 times, p< 0.05). Total SBF of the 45 mm cup ((24.33 ± 8.72) × 103 times) was significantly higher than the 35 mm cup ((8.05 ± 1.63) × 103 times, p< 0.05). Recovery time of the 45 mm cup (287.46 ± 39.54 seconds) was significantly longer than the 35 mm cup (180.12 ± 1.42 seconds, p< 0.05). CONCLUSIONS: Our results show that all three cup sizes can significantly increase SBF. The 45 mm cup is more effective in increasing SBF compared to the 35 mm cup.

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Changes in rat mesentery interstitial matrix due to superfusate

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.265.3.h852 ◽

1993 ◽

Vol 265 (3) ◽

pp. H852-H856 ◽

Cited By ~ 3

Author(s):

B. J. Barber ◽

R. A. Babbitt ◽

S. Dutta ◽

S. Parameswaran

Keyword(s):

Protein Content ◽

Normal Saline ◽

Protein Concentration ◽

Matrix Protein ◽

Protein Transport ◽

Albumin Concentration ◽

Sprague Dawley ◽

Tissue Samples ◽

Rat Mesentery ◽

Sprague Dawley Rats

Animal preparations for microscopy often require a superfusate solution to cover surgically exposed tissue. There are few, if any, data concerning the effects of this solution on extravascular protein concentration and hydration. The effect of superfusion on mesenteric tissue in anesthetized male Sprague-Dawley rats was studied. Tissue samples were taken from nonsuperfused and superfused tissue and analyzed for hydration, albumin, and transferrin content. The mesenteric tissue interstitial matrix was rapidly altered by normal saline superfusate. After superfusion, there was a decrease (P < 0.01) in tissue albumin concentration from 1.17 +/- 0.27 to 0.10 +/- 0.08 g/dl (n = 9). Tissue hydration increased from 4.98 +/- 0.8 micrograms water/microgram dry wt in controls to 7.38 +/- 1.2 micrograms water/micrograms dry wt after superfusion. When a range of superfusate albumin concentrations was used (0, 1, 2, and 3 g/dl), tissue albumin concentration changed 0.59 +/- 0.09 g/dl for each gram per deciliter change in superfusate concentration (P < 0.0001). The large changes in interstitial matrix protein content and hydration suggest that superfusate solution effects need to be considered in microvascular protein transport experiments.

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