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Stomach of the rat which received opipramol (25, 50 and 100 mg/kg)＋indomethacin (A, B, C), ranitidine (25 mg/kg)＋indomethacin (D) and (E) only-indomethacin
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Tricyclic antidepressants are particularly useful in the treatment of endogenous depression. Since the 1950s, tricyclic antidepressants (TCAs) have also been used for the treatment of gastric ulcer disease. Many TCAs have been evaluated for their antiulcer effects, but there are presently no data in the literature specifically concerning the antide...
Citations
... Some studies have suggested that the relaxation of the sphincter, as evidenced by urethral pressure measurements during bladder filling, can lead to a squeezing sensation, with afferent neurons also contributing to this sensation (2). Bladder relaxants can be beneficial in alleviating symptoms of an overactive bladder and reducing urinary incontinence (3). Antidepressant drugs are known to inhibit the bladder via their antimuscarinic effects (4). ...
... However, oral administration of indomethacin has been associated with systemic and local upper gastrointestinal side effects, such as erosions, ulcerative lesions, and petechial bleeding in the mucosa of the stomach [19][20][21]. Other studies show that the oral administration of indomethacin in rats and humans causes ulcerative lesions in the gastric mucosa stemming from the generation of reactive oxygen species and lipid peroxidation [22][23][24]. ...
Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (C1), a new 5-aminosalicylic acid (5-ASA) derivative, has proven to be an antioxidant in vitro and an anti-inflammatory agent in mice. The in vivo inhibition of myeloperoxidase was comparable to that of indomethacin. The aim of this study was to take another step in the preclinical evaluation of C1 by examining acute toxicity with the up-and-down OECD method and pharmacokinetic profiles by administration of the compound to Wistar rats through intravenous (i.v.), oral (p.o.), and intraperitoneal (i.p.) routes. According to the Globally Harmonized System, C1 belongs to categories 4 and 5 for the i.p. and p.o. routes, respectively. An RP-HPLC method for C1 quantification in plasma was successfully validated. Regarding the pharmacokinetic profile, the elimination half-life was approximately 0.9 h with a clearance of 24 mL/min after i.v. administration of C1 (50 mg/kg). After p.o. administration (50 mg/kg), the maximum plasma concentration was reached at 33 min, the oral bioavailability was about 77%, and the compound was amply distributed to all tissues evaluated. Therefore, C1 administered p.o. in rats is suitable for reaching the colon where it can exert its effect, suggesting an important advantage over 5-ASA and indomethacin in treating ulcerative colitis and Crohn’s disease.
... Neutrophil polymorph and chronic inflammatory cell infiltration are consequences of the mucosal immune response to bacterial antigens. Dursun et al. (2009) referred the ability of neutrophils to release inflammatory mediators and potent reactive oxygen species such as superoxide, hydrogen peroxide, and MPO that are coinciding with our results. Abdulla et al. (2010) demonstrated that the reduction of neutrophil infiltration in the ulcerated gastric tissue promoted the prevention of gastric lesions. ...
Gastric ulcer is a worldwide disease. Helicobacter pylori is one of the most common chronic bacterial infections that induce chronic inflammation in the gastric mucosa, mediated by an array of pro-and inflammatory cytokines. The aim of this study was to investigate the possible therapeutic effects of Ginkgo biloba extract on gastric ulcer induced by ammonium hydroxide in rats and the potential underlying mechanisms. The study was done on 32 adult male Wistar albino rats, divided equally into 4 groups: normal control, gastric ulcer–induced group using 1 ml of 1% NH4OH orally, ulcer control group; rats received 1% carboxymethyl cellulose daily for 14 days after induction of ulcer and treated rats received orally 200 mg/kg Ginkgo biloba once daily for 14 days after induction of ulcer. The study revealed administration of ammonia showed multiple gastric lesions; edema, hyperemia, hemorrhage, and ulcers with a significant increase in ulcer score, myeloperoxidase (MPO), and interleukin-1β (IL-1β) and a significant decrease in reduced glutathione (GSH), mucus amount, and gastric pH. After the administration of Ginkgo biloba, there was an improvement in gastric lesions, with a significant reduction of ulcer score, MPO, and IL-1β and a significant increase in GSH, mucus content, and gastric pH. Moreover, collagen types I and IV were gradually increased in the treated group.
... As shown in the present investigation, ranitidine treatment significantly reversed the ethanol-induced changes in MDA and TAC, which is in agreement with Dursun et al. (2009). Moreover, the study of Sharkawi et al. (2012), who postulated that this significant MDA reduction suggested decreased lipid peroxidation and antioxidant activity by ranitidine. ...
The prevention of gastric ulcer pathogenesis or its recurrence is currently one of the main goals of clinical and experimental studies. This study was conducted to investigate the gastroprotective effects of ursolic acid (UA) isolated from the dichloromethane/methanol extract of shoots of Ochrosia elliptica Labill. and investigated for its activity against an ethanol-induced gastric ulcer model in rats. Fifty-six female albino rats were divided into seven groups (eight rats per group): The first group served as control; group 2: absolute ethanol group (5 ml/kg. b.w.); group 3: ranitidine pretreated group (50 mg/kg, i.p.); group 4: UA (100 mg/kg, b.w.); and groups from 5 to 7 were pretreated with UA (25, 50, and 100 mg/kg, b.w.). Then, all animals were sacrificed, and the stomachs were excised for examination. Gastric mucosal injuries were assessed by gross examination, histopathology, immunohistochemistry of caspase-3, and biochemical parameters, including tissue malondialdehyde (MDA) and total antioxidant capacity (TAC) levels. The ethanol group showed severe mucosal injury compared with UA-treated animals, which grossly showed significant reductions of ulcer areas. Histopathologically, they showed marked reductions of mucosal necrosis, edema, and leukocyte infiltrations. Significant increased TAC levels were associated with reduced MDA levels UA-treated rats. In addition, the caspase-3 activity was downregulated. These findings indicated gastroprotective effects of UA at the administered doses comparable with that observed with the control drug ranitidine through suppression of mucosal oxidative stress and antiapoptotic activities. Molecular docking studies showed that UA binds to H+/K+ ATPase more than omeprazole and ranitidine −9.23 vs. −7.09 and 6.29 kcal/mol). In addition, the pKi value of UA was also lower than omeprazole and ranitidine (169.6 nM vs. 6.3 and 26.7 µM). The molecular docking findings suggested the protection role of UA against ethanol-induced gastric ulcer.
... In experimental oxidative stress-induced rats with N ω -Nitro-L-arginine methyl ester hydrochloride (L-NAME) were reported that the ellagic acid was increased superoxide production in the vascular tissue, plasma MDA levels as a marker of lipid peroxidation and reactive oxygen species and decreased expression of p47 phox subunit of NADPH oxidase responsible for hypertension. It has also been claimed that ellagic acid in rats causes these effects when the NO ratio restores according to the optimum living conditions [24]. The findings of present study support previous studies on oxidative stress. ...
Non-steroidal anti-inflammatory drugs (NSAIDs) commonly used by people induces gastric injury. This study was designed to evaluate effects of ellagic acid as a natural compound on oxidative stress markers and immunohistochemical structure during experimental gastric damage. It was created five groups as follows. Group I was received standard pellet feed and drinking water. On the other hand, a single oral dose of 25 mg/kg indomethacin, 10 mg/kg ellagic acid, 25 mg/kg indomethacin plus 10 mg/kg ellagic acid and 20 mg/kg omeprazole were received to group II, III, IV and V, respectively. The reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), total sialic acid (TSA) and ghrelin levels of samples taken after 6 hours from applications were analyzed by spectrophotometric methods. The cyclooxygenase 2 (COX-2) reactivity was analyzed by immunohistochemical staining method. The kidney NO and TSA levels of group II were found to be increased compared with group I, whereas these levels were lower in group IV compared with group II. The liver NO and MDA levels of group II were higher than in group IV. All blood ghrelin levels in group II were lower compared with other groups. It was revealed severe COX-2 immunoreactivity in stomach surface and foveola epithelium, parietal cells, macrophages and vascular endothelium near submucosa of group II, while this reactivity was less in group IV. It was concluded that ellagic acid significantly changed NO, TSA, MDA and ghrelin levels and stomach COX-2 activity of mice given indomethacin and ellagic acid prevented gastric injury.
Keywords: Gastric injury; ellagic acid; indomethacin; oxidative stress; cyclooxygenase.
... In experimental oxidative stress-induced rats with N ω -Nitro-L-arginine methyl ester hydrochloride (L-NAME) were reported that the ellagic acid was increased superoxide production in the vascular tissue, plasma MDA levels as a marker of lipid peroxidation and reactive oxygen species and decreased expression of p47 phox subunit of NADPH oxidase responsible for hypertension. It has also been claimed that ellagic acid in rats causes these effects when the NO ratio restores according to the optimum living conditions [24]. The findings of present study support previous studies on oxidative stress. ...
Non-steroidal anti-inflammatory drugs (NSAIDs) commonly used by people induces gastric injury. This study was designed to evaluate effects of ellagic acid as a natural compound on oxidative stress markers and immunohistochemical structure during experimental gastric damage. It was created five groups as follows. Group I was received standard pellet feed and drinking water. On the other hand, a single oral dose of 25 mg/kg indomethacin, 10 mg/kg ellagic acid, 25 mg/kg indomethacin plus 10 mg/kg ellagic acid and 20 mg/kg omeprazole were received to group II, III, IV and V, respectively. The reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), total sialic acid (TSA) and ghrelin levels of samples taken after 6 hours from applications were analyzed by spectrophotometric methods. The cyclooxygenase 2 (COX-2) reactivity was analyzed by immunohistochemical staining method. The kidney NO and TSA levels of group II were found to be increased compared with group I, whereas these levels were lower in group IV compared with group II. The liver NO and MDA levels of group II were higher than in group IV. All blood ghrelin levels in group II were lower compared with other groups. It was revealed severe COX-2 immunoreactivity in stomach surface and foveola epithelium, parietal cells, macrophages and vascular endothelium near submucosa of group II, while this reactivity was less in group IV. It was concluded that ellagic acid significantly changed NO, TSA, MDA and ghrelin levels and stomach COX-2 activity of mice given indomethacin and ellagic acid prevented gastric injury.
Keywords: Gastric injury; ellagic acid; indomethacin; oxidative stress; cyclooxygenase.
... [32] Ranitidine is a reversible, competitive blocker of histamine at H 2 receptor on the parietal cells to decrease gastric acid secretion, reduce gastric juice volume, and reduce H+ concentration. [33,34] Based on these potentials, it probably explains why in this study, macroscopic and histologic damages in the gastric mucosa of ranitidine-treated group was reduced when compared with control. ...
Objectives: The modulation of vascular endothelial growth factor, antioxidants, and tissue necrosis factor alpha (TNF-α) using ethanol stem bark extract of Boswellia dalzielii H. was evaluated in an ethanol-induced gastric ulcer al-bino rat model. Methods: Thirty albino rats of either sex (200-250 g) were starved for 48 h but were allowed drinking water with 8% sucrose to avoid dehydration. The rats were placed on wire gauze above the base of the cage to prevent coprophagy. At the end of the fasting period, the rats were equally divided and assigned to six treatment groups. Group A served as control and 5 ml/kg distilled water was orally administered to the rats without further treatment. Rats in group B were given 5 ml/kg distilled water and served as negative control. Rats in groups C, D, and E were pretreated with 100, 200, and 400 mg/kg of the ethanol stem bark extract of B. dalzielii H, respectively. Group F received 50 mg/kg ranitidine. After 1 h, all the rats in groups B-F were each given absolute ethanol 1 ml/200 g body weight of rat. All treatments were by intragastric lavage. One hour after the treatment with ethanol, all the rats in the experiment (groups A-F) were eutha-nized with an overdose of anesthetic ether and their stomachs were excised. The stomachs were cut along the greater curvature and washed in warm normal saline. Each stomach was stretched out and pinned on board. Results: The results of the study revealed that pretreatment with ethanol stem bark extract of B. dalzielii H. decreased gross and histological gastric mucosal damage caused by intragastric administration of absolute ethanol in a dose-dependent manner when compared with controls. The gastric ulcer index and gastric tissue level of malondialdehyde (MDA) and TNF-α were significantly reduced (p<0.001), whereas the gastric tissue level of superoxide dismutase, cata-lase, total antioxidant capacity, and vascular endothelial growth factor (VEGF) was significantly increased (p<0.001) when compared with the controls. Conclusion: The plant extract attenuated gastric mucosal damage induced by ethanol via upregulation in the expression of gastric tissue VEGF, reinforcement of the antioxidant system, and reduction in the gastric tissue level of MDA and the pro-inflammatory cytokine TNF-α.
... [32] Ranitidine is a reversible, competitive blocker of histamine at H 2 receptor on the parietal cells to decrease gastric acid secretion, reduce gastric juice volume, and reduce H+ concentration. [33,34] Based on these potentials, it probably explains why in this study, macroscopic and histologic damages in the gastric mucosa of ranitidine-treated group was reduced when compared with control. ...
... Some possible indications for opipramol are still the m atter o f research. Animal studies suggest that there could be a possible clinical appli cation in peptic ulcer patients with a comorbid depression (Dursun 2009). Opipramol, as potent sigma ligand, could theoretically be an anti-ischemic agent helpful in neurological conditions (Rao 1990). ...
Opipramol is considered as a pharmacological agent that does not fit the classification taking into account the division of antidepressants, antipsychotics and anxiolytics. It has a structure related to tricyclic antidepressants but it has a different mechanism of action, i.e. binding to sigma1 and to sigma2 sites. It has been regarded as an effective drug in general anxiety disorders together with other agents like SSRI`s, SNRI`s, buspirone and pregabalin for many years. It can however also be indicated in other conditions, e.g. it may be used as a premedication in the evening prior to surgery, positive results are also observed in psychopharmacological treatment with opipramol in somatoform disorders, symptoms of depression can be significantly reduced in the climacteric syndrome. The latest data from literature present also certain dangers and side effects, which may result due to opipramol administration. Mania may be induced not only in bipolar patients treated with opipramol, but it can be an adverse drug reaction in generalized anxiety disorder. This analysis shows however that opipramol is an important drug still very useful in different clinical conditions.
... Some possible indications for opipramol are still the m atter o f research. Animal studies suggest that there could be a possible clinical appli cation in peptic ulcer patients with a comorbid depression (Dursun 2009). Opipramol, as potent sigma ligand, could theoretically be an anti-ischemic agent helpful in neurological conditions (Rao 1990). ...
Opipramol is considered as a pharmacological agent that does not fit the classification taking into account the division of antidepressants, antipsychotics and anxiolytics. It has a structure related to tricyclic antidepressants but it has a different mechanism of action, i.e. binding to sigma1 and to sigma2 sites. It has been regarded as an effective drug in general anxiety disorders together with other agents like SSRI`s, SNRI`s, buspirone and pregabalin for many years. It can however also be indicated in other conditions, e.g. it may be used as a premedication in the evening prior to surgery, positive results are also observed in psychopharmacological treatment with opipramol in somatoform disorders, symptoms of depression can be significantly reduced in the climacteric syndrome. The latest data from literature present also certain dangers and side effects, which may result due to opipramol administration. Mania may be induced not only in bipolar patients treated with opipramol, but it can be an adverse drug reaction in generalized anxiety disorder. This analysis shows however that opipramol is an important drug still very useful in different clinical conditions.
