Biochemical and pharmacological characteristics of a newly synthesized H+-K+ ATPase inhibitor, YJA20379-1, 2-amino-4,5-dihydro-8-phenylimidazole [2,1-b]thiazolo[5,4-g]benzothiazole

1999 ◽  
Vol 77 (5) ◽  
pp. 330-338
Author(s):  
Sang-Kwon Sohn ◽  
Man-Sik Chang ◽  
Wahn-Soo Choi ◽  
Kyu-Bong Kim ◽  
Tae-Wook Woo ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Inhibitory Activity ◽  
Water Immersion ◽  
Gastric Ulcers ◽  
Sprague Dawley ◽  
Atpase Inhibitor ◽  
Duodenal Ulcers ◽  
Cytoprotective Activity ◽  
Sprague Dawley Rats ◽  
Potent Inhibitory Activity

The biochemical and pharmacological characteristics of a newly synthesized H+-K+ ATPase inhibitor, 2-amino-4,5-dihydro-8-phenylimidazole[2,1-b]thiazolo[5,4-g]benzothiazole (YJA20379-1), were investigated. In the pig gastric microsomes, YJA20379-1 inhibited the gastric H+-K+ ATPase regardless of pH condition, IC50 values being 21 and 24 µM at pH 6.4 and 7.4, respectively. The inhibitory activity of YJA20379-1 was antagonized by dithiothreitol treatment but could not be reversed by dilution and washing of the enzyme preparation. In Sprague-Dawley rats, YJA20379-1, administered i.d., p.o, i.v., or s.c., significantly inhibited basal gastric acid secretion, with ED50 values of 4.7, 20.2, 6.3, and 13.4 mg/kg, respectively. The antisecretory action of YJA20379-1 was short lasting (less than 7 h at an oral dosing of 30 mg/kg). Oral administration of YJA20379-1 also prevented the formation of ethanol, indomethacin, and water immersion stress induced gastric lesions and mepirizole-induced duodenal ulcers in rats. Furthermore, YJA20379-1 accelerated the healing of acetic acid induced chronic gastric ulcers in rats. In conclusion, these results suggest that YJA20379-1 has a potent inhibitory activity on the gastric H+-K+ ATPase but much shorter duration of antisecretory action than omeprazole, thereby exerting its anti-ulcer effects partly with cytoprotective activity.Key words: proton pump inhibitor, acid secretion, anti-ulcer effects, cytoprotective activity.

The biochemical and pharmacological properties of a newly synthesized H+-K+ ATPase inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol-[1,2-a]benzimidazole

1998 ◽  
Vol 76 (9) ◽  
pp. 921-929 ◽  
Author(s):  
Young-Kuk Chung ◽  
Man-Sik Chang ◽  
Kyu-Bong Kim ◽  
Sang-Kwon Sohn ◽  
Tae-Wook Woo ◽  
...  
Keyword(s):  
Proton Pump Inhibitor ◽  
Atpase Activity ◽  
Acid Secretion ◽  
Proton Pump ◽  
Water Immersion ◽  
Repeated Administration ◽  
Gastric Ulcers ◽  
Dependent Manner ◽  
Atpase Inhibitor ◽  
Concentration Dependent Manner

This study was designed to determine the effect of a newly synthesized proton pump inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol[1,2-a]benzimidazole (YJA20379-2), on gastric H+-K+ ATPase activity, acid secretion, and experimental gastroduodenal lesions or ulcers in rats. YJA20379-2 inhibited in a concentration-dependent manner the proton pump (H+-K+ ATPase) activity in isolated hog gastric mucosal microsomes, therefore, confirming its classification as a proton pump inhibitor. The inhibitory efficacy of YJA20379-2 on the proton pump was about eight times higher than that of omeprazole at pH 7.4. The activity of the inhibited enzyme was not restored by dilution and washout method, so this implied that the inhibition of YJA20379-2 is not reversible. YJA20379-2, given intraduodenally or orally, potently suppressed acid secretion in pylorus-ligated rats, with ED50 values of 3.6 and 7.7 mg·kg-1, respectively. Pretreatment with YJA20379-2 dose dependently protected the gastric mucosa from damage induced by absolute ethanol, water-immersion stress, indomethacin, and the duodenal mucosa from damage induced by mepirizole in rats, with ED50 values of 11.0, 21.0, 0.5, and 18.7 mg·kg-1, respectively. Repeated administration of YJA20379-2 also dose dependently accelerated spontaneous healing of acetic acid induced gastric ulcers. These results suggest that YJA20379-2 has potent antisecretory and antiulcer effects, which are exerted by suppression of H+-K+ ATPase activity in gastric parietal cells, such that YJA20379-2 may be useful for the clinical treatment of peptic ulcer diseases.Key words: antisecretion, cytoprotection, H+-K+ ATPase, YJA20379-2.

scholarly journals The Protective Effect of Testosterone on Indomethacin Induced Gastric Ulcer in Female Sprague Dawley Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
U. Akpamu ◽  
H. O. Otamere ◽  
I. O. Ernest-Nwoke ◽  
C. N. Ekhator ◽  
U. C. Osifo
Keyword(s):  
Gastric Ulcer ◽  
Female Rats ◽  
Gastric Ulcers ◽  
Standard Laboratory ◽  
Sprague Dawley ◽  
Gastric Mucus ◽  
Ulcer Index ◽  
Sprague Dawley Rats ◽  
Group A ◽  
Group B

Gastric ulcer has shown association with changes in sex hormones, with impact exacerbated in males. Also, males are known to be more exposed to ulcer risk factors. This study investigates the effect of testosterone on indomethacin induced gastric ulcers in adult female rats. Eighteen female rats (225 ± 25 g body weight) were randomly assigned to 3 groups under standard laboratory condition. After acclimatization, animals fasted for 40 hrs but were given water ad libitum. Group A served as control while group B served as the ulcer control, in which ulcer was induced without treatment using indomethacin (40 mg/kg single orally dose). Group C was pretreated with testosterone (1 mg/kg IM) eight hours before ulcer induction. Eight hours after ulcer induction, animals were sacrificed and the stomach was harvested for analysis. Results showed a significant reduction in mucus content in groups C (0.79±0.11 g) and B (0.87±0.02 g) compared to A (1.11±0.03 g). Gastric mucus pH was significantly acidic in group B (4.40±0.55) compared to C (5.20±0.45) and A (5.80±0.45). There was a significantly higher ulcer index in group B (4.60±0.55 mm) compared to C (3.60±0.89 mm) and testosterone pretreatment resulted in a 21.74% ulcer inhibition. Although weak, the findings suggest that testosterone might protect the gastric mucosa against NSAIDs in females.

scholarly journals Anxiolytic Effects of Acanthopanax senticosus HARMS Occur via Regulation of Autonomic Function and Activate Hippocampal BDNF–TrkB Signaling

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 132 ◽  
Author(s):  
Shouhei Miyazaki ◽  
Hirotaka Oikawa ◽  
Hideo Takekoshi ◽  
Masako Hoshizaki ◽  
Masato Ogata ◽  
...  
Keyword(s):  
Autonomic Function ◽  
Nervous Activity ◽  
Anxiolytic Effect ◽  
Gastric Ulcers ◽  
Sympathetic Nervous Activity ◽  
Sprague Dawley ◽  
Bdnf Expression ◽  
Acanthopanax Senticosus ◽  
Sprague Dawley Rats ◽  
Bdnf Signaling

Mental stress, such as anxiety and conflict, causes physiological changes, such as changes in autonomic nervous activity and gastric ulcers. In addition, stress induces glucocorticoids and changes the hippocampal brain-derived neurotrophic factor (BDNF) expression levels. We previously reported that Acanthopanax senticosus HARM (ASH) prevents stress-induced gastric ulcers. Thus, we investigated the potential anxiolytic effect and influence of ASH on the hippocampus BDNF-related protein in male Sprague-Dawley rats fed 1% and 5% ASH extract-containing food for one week using novelty suppressed feeding (NSF) and improved elevated beam walking (IEBW) tests. ASH treatment significantly decreased latency to eat in the NSF test and increased the time spent on the open arm in the IEBW test. ASH5% treatment showed a significant decrease in LFnu, indicative of sympathetic nervous activity, and a significant increase in HFnu, indicative of parasympathetic nervous activity, in the NSF test. In addition, ASH1% and ASH5% treatments significantly decreased LFnu and significantly increased HFnu in the IEBW test. ASH5% treatment significantly increased hippocampal BDNF protein expression in both Western blotting and immunohistochemistry experiments. Our findings suggest that anxiolytic effects of ASH occur via the regulation of autonomic function and increased hippocampal BDNF signaling.

Ultrastructural study of experimental duodenal ulcer in a new animal model

1992 ◽  
Vol 50 (1) ◽  
pp. 614-615
Author(s):  
H.X. Bui ◽  
A. delRosario ◽  
M. Abdulla ◽  
F. Ballouk ◽  
V. Bajakian ◽  
...  
Keyword(s):  
Duodenal Ulcer ◽  
Electron Microscope ◽  
Gastric Ulcers ◽  
Ultrastructural Changes ◽  
Sprague Dawley ◽  
Polyethylene Tube ◽  
Duodenal Ulcers ◽  
Thin Sections ◽  
Experimental Duodenal Ulcer ◽  
Scanning Electron

Various animal models have often been utilized as the basis of studies of the pathophysiology of peptic ulcer disease, however the ultrastructural changes in the evolution of duodenal ulcers produced in experimental animals have not been well elucidated. Utilizing a surgical method developed for the study of gastric ulcers we have established an experimental duodenal ulcer production technique in the rat which is highly reproducible and readily standardized. In the following time sequence study of experimental duodenal ulcers we present the ultrastructural features of ulcer induction and evolution.Duodenal ulcers were produced in 150-200 gram male Sprague Dawley rats by application of 50% acetic acid for 30 seconds through a 3 mm polyethylene tube to the serosa 1.0-1.5 cm distal to the pyloric sphincter. Routine transmission and scanning electron microscopy were performed on duodenal specimens at specific time points subsequent to surgical ulcer generation. Thin sections were stained with uranyl acetate and lead citrate and examined with a Phillip's EM 300 transmission electron microscope. For SEM, specimens were post-fixed in 2% osmium for two days, coated with gold/palladium and examined with JEOL JSM-6100 scanning electron microscope (JEOL, Inc., Peabody, MA).

Effect of Ascorbic Acid on Pituitary Weight during Stress

1986 ◽  
Vol 58 (1) ◽  
pp. 173-174 ◽  
Author(s):  
John H. Richardson
Keyword(s):  
Ascorbic Acid ◽  
Water Immersion ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

40 Sprague-Dawley rats were subjected to stress by crowding and water immersion for five days. Three groups of animals were compared: controls ( n = 20), stressed animals dosed with ascorbic acid ( n = 20), and stressed animals not dosed with ascorbic acid ( n = 20). Ascorbic acid prevented both adrenal and pituitary hypertrophy in stressed animals. Ascorbic acid appears to act as a potentiating factor for ACTH when there is an increased demand for ACTH during stress.

Gastroprotective Effect of Thymoquinone on Water Immersion Restraint Stress Induced Ulceration in Rats

Drug Research ◽  
2017 ◽  
Vol 67 (06) ◽  
pp. 366-372 ◽  
Author(s):  
Syed Ahmad ◽  
Abul Najmi ◽  
Madhu Kaundal ◽  
Mohd Akhtar
Keyword(s):  
Oxidative Stress ◽  
Acid Secretion ◽  
Gastric Juice ◽  
Acid Output ◽  
Water Immersion ◽  
Treated Group ◽  
Gastric Ulcers ◽  
Combination Group ◽  
Albino Rats ◽  
Ulcer Index

Abstract To evaluated the role of thymoquinone (TQ) on stress induced ulceration progress in rats subjected to water immersion restraint as a stress (WRS) condition model. Wistar albino rats were divided into different groups; the animals were subjected to WRS. TQ (10 mg/kg) alone and TQ with ranitidine (20 mg/kg) were administered per orally as pre treatment for 7 days. On 8th day the animals were sacrificed, gastric juice, pH, acid secretion, acid output, ulcer index and markers of oxidative stress and histopathology were determined. Volume of gastric juice, acid secretion was increased, while pH decreased in WRS animals. TQ pre-treated group showed reduction in the above parameters. The combination group showed more significant results than TQ and ranitidine alone on the above parameters. TQ decreased the ulcer index (UI), again combination group showed more significant decreased in UI. Oxidative stress markers were reduced and antioxidant enzymes were augmented. Gastric mucosa was protected as demonstrated by histological slides. The present study is one of its kinds to demonstrate anti ulcer effect of TQ against the water immersion restraint method of stress ulceration. Thus, TQ has the potential to be the promising drug for stress induced gastric ulcers.

scholarly journals Endogenous cardiotonic steroids and vascular fibrosis in preeclampsia

2019 ◽  
Vol 24 (6) ◽  
pp. 684-692 ◽  
Author(s):  
N. I. Agalakova ◽  
V. A. Reznik ◽  
O. V. Nadei ◽  
I. A. Ershov ◽  
O. S. Rassokha ◽  
...  
Keyword(s):  
Fold Increase ◽  
Normal Subjects ◽  
Negative Regulator ◽  
Sprague Dawley ◽  
Atpase Inhibitor ◽  
Relaxant Effect ◽  
Sprague Dawley Rats ◽  
Gestation Age ◽  
Umbilical Arteries ◽  
Design And Methods

Background. Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). Recently, we demonstrated that MBG induces fibrosis in cardiovascular tissues via mechanism involving inhibition of Fli1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis.Objective.We hypothesized that in human and rat PE, elevated MBG level is associated with development of fibrosis of umbilical arteries and rat thoracic aortae.Design and methods.Twelve patients with PE (mean blood pressure (BP) 118 ± 4 mmHg; mean age 28 ± 2 years; mean gestation age 36 ± 1 weeks) and 12 gestational age-matched normal pregnant subjects (mean BP 92 ± 2 mmHg; mean age 26 ± 1 years; mean gestation age 37 ± 1 weeks) were enrolled in the clinical study. We tested 16 pregnant Sprague-Dawley rats. Hypertension was provoked in 8 rats by 1,8 % Na supplementation.Results.PE in humans and rats was associated with the higher plasma MBG level and was associated with five-fold decrease in Fli-1 level and four-fold increase in collagen-1 level in the PE umbilical arteries vs. those from the normal subjects (p < 0,01). Isolated rings of umbilical arteries from the subjects with PE exhibited impaired response to the relaxant effect of sodium nitroprusside vs. control vessels (EC50 = 141 nmol/L vs. EC50 = 0,9 nmol/L; p < 0,001). Similar results were obtained for thoracic aorta of rats with experimental PE.Conclusions. These results demonstrate that elevated MBG level is implicated in the development of fibrosis umbilical arteries in PE. 

Histologic and Ultrastructural Features of Experimental Duodenal Ulcers in Sprague-Dawley Rats

1993 ◽  
Vol 59 (2) ◽  
pp. 136-154 ◽  
Author(s):  
Hai X. Bui ◽  
C.Y. Lee ◽  
Arthur del Rosario ◽  
Mohamed Abdulla ◽  
Fayez Ballouk ◽  
...  
Keyword(s):  
Sprague Dawley ◽  
Duodenal Ulcers ◽  
Sprague Dawley Rats ◽  
Experimental Duodenal Ulcers
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