Reserpine-induced Gastric Ulcers Research Articles

White tea (Camellia sinenesis (L.)) ethanol extracts attenuate reserpine-induced gastric ulcers in mice

The gastroprotective effect of white tea extract ethanol (WTEE) on reserpine induced gastric ulcers in KM mice was investigated. Gastric juice secretion, the pH of gastric juice, serum neuropeptides, including motilin (MOT), substance P (SP), vasoactive intestinal peptide (VIP), and somatostatin (SS) levels, and serum levels of the inflammatory cytokines TNF-α, IL-6, IL-12, and IFN-γ were measured. WTEE dose-dependently reduced reserpine-induced gastric juice secretion and increased the pH of gastric juice. WTEE increased serum levels of VIP and SS and reduced levels of MOT, SP, and inflammatory cytokines in the serum. WTEE modulated gastric expression of occludin and p38 phosphorylation in ulcer-bearing mice. WTEE has a gastroprotective effect against reserpine-induced gastric ulcers in KM mice via reduction of gastric juice secretion, modulation of serum neuropeptide levels, attenuation of serum inflammatory cytokines, and regulation of gastric levels of occludin and p38 phosphorylation.

Antioxidant-mediated preventative effect of Dragon-pearl tea crude polyphenol extract on reserpine-induced gastric ulcers.

Dragon-pearl tea is a type of green tea commonly consumed in Southwest China. In the present study, the antioxidative and anti-gastric ulcer effects of Dragon-pearl tea crude polyphenols (DTCP) were determined in vitro and in vivo. Treatment with 25, 50 or 100 µg/ml DTCP resulted in notable antioxidant effects in vitro, which manifested as 2,2-diphenyl-1-picrylhydrazyl and OH radical-scavenging activity. Furthermore, using an in vivo mouse model, DTCP was shown to reduce the gastric ulcer area in the stomach, in which the 200 mg/kg DTCP dose exhibited the most marked effect, with a gastric ulcer index inhibitory rate of 72.63%. In addition, DTCP was demonstrated to improve stomach acidity conditions in vivo by increasing the pH and reducing the level of gastric juice, as compared with the reserpine-induced gastric ulcer control mice. Furthermore, DTCP altered the serum levels of a number of oxidation-related biomolecules, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), lipid peroxidation (LPO) and catalase (CAT), to subsequently exert an anti-gastric ulcer effect. Treatment with 50, 100 and 200 mg/kg DTCP increased the SOD, GSH-Px and CAT levels and reduced the MDA and LPO levels in the mouse model of gastric ulcers. These serum level alterations resulted in the modified serum levels of prostaglandin E2 (PGE2) and nitric oxide (NO), which are associated with gastric mucosal protection. A reverse transcription-quantitative polymerase chain reaction (RT-PCR) assay is a molecular biology experiment which could determine the changes of mRNA in tissues. Using the RT-PCR assay, DTCP was observed to increase the mRNA expression levels of certain genes associated with gastric ulcers: Epidermal growth factor, epidermal growth factor receptor, vascular endothelial growth factor and vascular endothelial growth factor receptor 1, while reducing gastrin expression levels. Therefore, the results indicated that DTCP induced a marked preventative effect on reserpine-induced gastric ulcers in vivo, as a result of its antioxidative capacity.

Gastroprotective Effects of Methanolic Extract ofSterculia nobilis Smith Seeds in Reserpine-Induced Gastric Ulcer in Mice

The aim of this study was to investigate the gastroprotective effect of methanolic extract from Sterculia nobilis Smith seeds (SSME) on reserpine (25 mg/kg)-induced gastric ulcer using an Institute of Cancer Research (ICR) mouse animal model. Gastric juice secretion, total acidity of gastric juice, serum neuropeptides, including motilin (MTL), substance P (SP), vasoactive intestinal peptide (VIP) and somatostatin (SS) levels, as well as gastric malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured. SSME effectively reduced reserpine-induced gastric juice secretion and decreased the total acidity in gastric juice. In addition, SSME reduced the serum levels of MTL and SP, and increased VIP and SS levels in serum. It also resulted in an increase in SOD and a reduction of MDA levels in gastric tissue. Results from the present study suggest that SSME has a gastroprotective effect on reserpine-induced gastric ulcer in mice by reducing gastric juice secretion, modulating serum neuropeptide levels, increasing the gastric SOD activity and attenuating the gastric MDA generation. Practical Applications The Sterculia nobilis Smith seed has been traditionally consumed as a fruit in South China, Vietnam, India and Indonesia. It has been demonstrated to exhibit numerous beneficial functions such as regulation of gastrointestinal function and improving eyesight.

Protective effect Malus pumila Mill leaf polyphenols in reserpine-induced gastric ulcer in mice

The protective effect of polyphenols from Malus pumila leaf (MALP) on reserpine (10 mg/kg)-induced gastric ulcer in Kunming (KM) mice was investigated. Gastric juice secretion, pH of gastric juice, serum neuropeptides, including motilin (MOT), substance P (SP), vasoactive intestinal peptide (VIP), and somatostatin (SS) levels, as well as serum levels of inflammatory cytokines (TNF-α, IL-6, IL-12, and IFN-γ) were measured. Gastric occludin and p38MAPK phosphorylation was analyzed by RT-PCR or Western blotting. MALP reduced reserpine-induced gastric juice secretion and increased the pH of gastric juice. MALP increased the serum levels of VIP and SS and reduced MOT, SP, and inflammatory cytokines in serum. It also modulated the gastric expression of occludin and p38MAPK phosphorylation in mice. These results suggest that MALP showed a protective effect against reserpine-induced ulcer in mice by reducing gastric juice secretion, modulating serum neuropeptide levels, attenuating serum inflammatory cytokines, and regulating gastric levels of occludin and p38MAPK phosphorylation.

Preventive effect of insect tea against reserpine-induced gastric ulcers in mice.

The aim of the present study was to determine the preventive effect of insect tea against reserpine-induced gastric ulcers in ICR mice. A high (800 mg/kg) dose of insect tea reduced the serum levels of the proinflammatory cytokines interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ compared with those in mice treated with a low (400 mg/kg) dose and the control mice. The serum levels of somatostatin (SS) and vasoactive intestinal peptide (VIP) in mice treated with insect tea were higher compared with those in the control mice; however, the serum levels of motilin (MOT) and substance P (SP) were lower in mice treated with insect tea than in the control mice. Gastric ulcer inhibitory rate of the insect tea treatment group of mice were much lower compared to the control mice, and the high concentration treated mice were similar to the ranitidine treated mice. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mice treated with insect tea were higher compared with those in control mice, and similar to those in normal mice and ranitidine-treated mice. The nitric oxide (NO) and maleic dialdehyde (MDA) levels of mice treated with a high concentration of insect tea compared with the normal group were close. Using quantitative polymerase chain reaction (qPCR) assays, the present study revealed that insect tea significantly induced inflammation in the tissues of mice by downregulating the expression of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and upregulating the expression of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor α (IκB-α). These results suggest that insect tea is as effective at preventing gastric ulcers as the gastric ulcer drug, ranitidine and it can be used as medicine.

Preventive activity of Ajuga pantantha Hand‐Mazz on reserpine‐induced experimental gastric ulcer in Kunming mice (647.8)

The aim of this study was to investigate the gastric ulcer preventive activity of aqueous extract from Ajuga pantantha Hand‐Mazz (AHMAE) on reserpine‐induced experimental gastric ulcer in Kunming mice. The mice were divided into the following five groups: normal, reserpine, 250 mg/kg and 500 mg/kg AHMAE and ranitidine. The mice were first treated with AHMAE for 28 days, and the gastric ulcer was induced by reserpine(10 mg/kg) via a intraperitoneal injection at day 29. Ranitidine (50 mg/kg) used as a positive control. Following intraperitoneal injection 24 h later, the area of gastric ulcer, gastric juice volume, gastric juice acidity, serum levels of MOT, SS, SP and VIP, serum pro‐inflammatory cytokines (IL‐6, IL‐12, TNF‐α and IFN‐γ), iNOS and COX‐2 gene expressions were analyzed. Following pretreatment with 250 and 500 mg/kg AHMAE significantly reduced the reserpine‐induced gastric ulceration. AHMAE also increased the serum SS and VIP and decreased the MOT and SP levels in serum. In addition, AHMAE significantly reduced the serum levels of pro‐inflammatory cytokines of IL‐6, 12, TNF‐α and IFN‐γ compared to control group. AHMAE also decreased the expression of iNOS and COX‐2. These results suggest that AHMAE showed a good gastric ulcer preventive effect.Grant Funding Source: Supported by the China Scholarship Council (No. [2012]5030) for fellowship

Preventive Effect of Polysaccharide of Larimichthys crocea Swim Bladder on Reserpine Induced Gastric Ulcer in ICR Mice.

This project's aim was to determine the reserpine-induced gastric ulcer preventive effect of polysaccharide of Larimichthys crocea swim bladder (PLCSB) in ICR mice. The anti-gastric ulcer effects of polysaccharide of Larimichthys crocea swim bladder was evaluated in mice model using morphological test, serum levels assay, cytokine levels assay, tissue contents analysis, reverse transcription-polymerase chain reaction (RT-PCR) analysis and western bolt assay. High concentration (50 mg/kg dose) of PLCSB reduced IFN-γ as compared to low concentration (25 mg/kg dose) and control mice. SS and VIP serum levels of PLCSB treated mice were higher than those of control mice, and MOT and SP serum levels were lower than control mice. Gastric ulcer inhibitory index of PLCSB treatment groups mice were much lower than control mice, and the high concentration treated mice were similar to the ranitidine treated mice. The SOD and GSH-Px activities of PLCSB treated mice were higher than control mice, close to normal mice and ranitidine treated mice. PLCSB treated mice also showed the similar contents of NO and MDA to normal group. By RT-PCR and western blot assay, PLCSB significantly induced inflammation in tissues of mice by downregulating NF-κB, iNOS, and COX-2, and upregulating IκB-α. These results suggest that PLCSB showed a good gastric ulcer preventive effect as the gastric ulcer drug of ranitidine. Polysaccharide of Larimichthys crocea swim bladder may be used as a drug material from marine products.

A study on the aetiology of reserpine ulceration and the antiulcer action of solcoseryl in rat stomach

The aetiology of reserpine-induced gastric ulcer formation and the antiulcer effects of solcoseryl were studied in rats. Intraperitoneal injection of reserpine produced severe ulceration, as well as mast cell and histamine depletion, in the gastric glandular mucosa. Mepyramine and cimetidine markedly antagonized the gastric lesions, but did not influence the reduced mast cell count; atropine pretreatment significantly inhibited both parameters. Intramuscular injection of solcoseryl lessened ulcer severity and prevented the decreased mast cell counts and histamine levels in reserpine-treated rats. However, the same dose of solcoseryl injected intraperitoneally was ineffective. Solcoseryl, irrespective of the route of administration, did not influence the gastric secretory activities of reserpine. It is concluded that reserpine ulceration is both cholinergic- and histamine-mediated, and that the antiulcer effects of solcoseryl appear to be due to prevention of histamine depletion in the gastric mucosa.

Effects of adrenomedullin on the contraction of gastric arteries during reserpine-induced gastric ulcer

Adrenomedullin (100 ng/kg, s.c.) prevents reserpine-induced damage of gastric mucosa. In the model of in vitro gastric arteries from reserpine-treated rats, adrenomedullin pre-treatment resulted in a decrease of the vasoconstriction in response to 5-hydroxytryptamine. In contrast, adrenomedullin pre-treatment of rat with intact gastric mucosa did not affect the vasoconstriction to 5-hydroxytryptamine. In the presence of the NOS inhibitor N G-nitro- l-arginine, the responsiveness to 5-hydroxytryptamine in gastric arteries from rats treated with reserpine+adrenomedullin was enhanced to the same level of rats treated with reserpine alone. The anti-ulcer effect of adrenomedullin could therefore be related, at least in part, to an increase of blood flow at the gastric mucosa, by a mechanism involving nitric oxide.

Gastric and jejunal serotonin content in rats with ethanol-induced ulcers: Effects of cinnarizine and sclareol glycol

The effects of graded doses of zinc sulfate pretreatment on reserpine-induced gastric ulceration and on lysosomal fragility both in vivo and in vitro, were studied in rats. Reserpine treatment (5 mg/kg, i.p., 18 h before sacrifice)_induced marked gastric glandular ulceration and elicited the release of free β-glucuronidase from lysosomes in the gastric mucosa. A similar effect on release of this enzyme from isolated rat hepatic lysosomes was observed after in vitro incubation with reserpine. Zinc sulfate (22, 44 or 88 mg/kg, i.p., 30 h before reserpinization, or 10−3 M in vitro)_inhibited the reserpine-induced response, and zinc sulfate alone (10−11−10−3 M) also stabilized lysosomal membrane permeability to β-glucuronidase. No direct effect of zinc or reserpine on purified β-glucuronidase activity was observed. In conclusion, it is postulated that the stabilizing effect of zinc on lysosomal membranes, as manifest by reduced release of β-glucuronidase from isolated lysosomes, is one of the protective mechanisms of zinc against reserpine-induced ulceration.

Protective effects of zinc L-carnosine (Z-103) on reserpine-induced gastric ulceration in rats

The present study examined the gastric protective effects of zinc L-carnosine (Z-103) in reserpinized rats. We also studied whether this antiulcer effect is related to the preservation of mast cells degranulation in the glandular mucosa. Reserpine administration (5 mg/kg, intraperitoneally [i.p.]) produced severe hemorrhagic glandular ulcers which were accompained with a marked decrease in mucosal mast cell counts. The severity of ulcers and mast cell degranulation were reduced by Z-103 when given orally 30 min before and 6 hr after reserpinization. However, this protection was not observed when the drug was administered as a single dose 30 min beforehand. The present findings extended the antiulcer action of Z-103 from stress- and ethanol-induced gastric damage to those on reserpine-provoked gastric ulcers. It also indicates that the protective action on reserpine ulceration is likely to be due to the stabilization on mast cell membrane in the glandular mucosa. © 1992 Wiley-Liss, Inc.

Role of Oxygen-Derived Free Radicals in the Mechanism of Chronic Gastric Ulceration in the Rat: Implications for Cytoprotection

Oxygen-derived free radicals are cytotoxic and mediate tissue damage. Allopurinol prevents the formation of superoxide radicals and dimethyl sulphoxide (DMSO) scavenges the hydroxyl ones. Intraperitoneal reserpine (5 mg/kg every day for 5 days) produced chronic gastric ulceration in all rats after 4 weeks. Animals gavaged with 1 ml/day of each of 1% allopurinol and 1% DMSO for 4 weeks developed ulceration in 60% of cases; however this ulceration developed in only 20% of animals similarly gavaged with 2% solutions. Rats gavaged with 1 ml/day of each of 5% allopurinol and 5% DMSO for 4 weeks were completely protected against the reserpine-induced chronic gastric ulceration. This protection was not associated with any significant effect on the H+ output of the rat stomach. The results suggest that in the rat, oxygen-derived free radicals are responsible for the development of chronic gastric ulceration and that removing these radicals protects against the said ulceration without influencing acid secretion, i.e. cytoprotection.

Effects of monoamine oxidase inhibitors, cholinolytics, and other pharmacologic agents on the ulcerogenic effects of reserpine in mice

Mice rather than rats [1-3] were employed in screening studies designed to define agents effective in protecting the gastric mucosa from the damaging effects of reserpine (RP); this approach allowed utilization of smaller quantities of the agents in question. The purpose of this study was to compare the antiulcerogenic efficacy of monoamine oxidase (~AO) inhibitors (iproniazid, Niamid, pargyline, phenylzin [4, 5]), m-cholinoblockers (atropine sulfate, metamizil HCI, and their iodomethylates), the catechol-o-methyltransferase (COMT) inhibitor depaverin [6], the adrenomimetic ephedrine and the centrally acting secretagogue 2-deoxy-D-glucose in reserpine-induced gastric ulcers in mice. Selection of the drugs was based on the observation that MAO inhibitors exerted a protective effect on reserpine-treated rats [7-9], ~lile the m-cholinolytics (atropine, metamizil) appeared to be ineffective in the prevention of RPinduced gastric lesions [9]. However, individual communications report on the antiulcerogenic effects of iproniazidand atropine in mice [i0]. Using the method developed by us for evaluating the ulcerogenicity of RP, we determined to uncover the most potent antiulcer agents from each group and compare them for their effectiveness on our RP ulcer model in the mouse.

Reserpine-induced gastric ulcers: Protection by lysosomal stabilization due to zinc

The effects of graded doses of zinc sulfate pretreatment on reserpine-induced gastric ulceration and on lysosomal fragility both in vivo and in vitro, were studied in rats. Reserpine treatment (5 mg/kg, i.p., 18 h before sacrifice)_induced marked gastric glandular ulceration and elicited the release of free β-glucuronidase from lysosomes in the gastric mucosa. A similar effect on release of this enzyme from isolated rat hepatic lysosomes was observed after in vitro incubation with reserpine. Zinc sulfate (22, 44 or 88 mg/kg, i.p., 30 h before reserpinization, or 10 −3 M in vitro)_inhibited the reserpine-induced response, and zinc sulfate alone (10 −11−10 −3 M) also stabilized lysosomal membrane permeability to β-glucuronidase. No direct effect of zinc or reserpine on purified β-glucuronidase activity was observed. In conclusion, it is postulated that the stabilizing effect of zinc on lysosomal membranes, as manifest by reduced release of β-glucuronidase from isolated lysosomes, is one of the protective mechanisms of zinc against reserpine-induced ulceration.

The protective role of the adrenal medulla against reserpine-induced gastric ulcers in rats

The influence of bilateral adrenalectomy or adrenal demedullation (carried out 48 h beforehand) on the 2-h gastric effects of i.p. injected reserpine (5 mg/kg) was studied in rats. Adrenalectomy or demedullation increased the severity of reserpine-induced gastric glandular lesions. Neither ablation method affected the stomach wall mast cell population nor the degree of reserpine-evoked mast cell degranulation. In contrast, both adrenalectomy and demedullation augmented druginduced glandular mucosal microcirculatory dilatation and engorgement. These results suggest that adrenal medullary catecholamines may antagonise, by a vasoconstrictor effect, the gastric glandular mucosal microcirculatory dilatation and congestion which are largely responsible for reserpine ulcers in the rat stomach. This protective effect is, however, overshadowed by the intense ulcerogenic action of the drug.

Effects of tandamine and pirandamine, selective blockers of biogenic amine uptake mechanisms, on gastric acid secretion and ulcer formation in the rat

Tandamine and pirandamine and various structurally-related compounds, which were known to inhibit the norepinephrine and/or serotonin uptake mechanisms, lack central anticholinergic activity and differ chemically from the known tricyclic antidepressant drugs, were examined for their effects on gastric acid secretion and ulcer formation in the rat. Tandamine and its structurally-related compounds, but not pirandamine or its structurally-related compound, given intraperitoneally, inhibited gastric acid secretion and were similar in activity to imipramine. Like imipramine, tandamine was effective when given perorally. None of the compounds examined, administered intraperitoneally, were effective in reducing the ulcer formation in 19 h pylorus-ligated animals, while imipramine was effective. Tandamine, like imipramine, inhibited ulcer formation in 10 h pylorus-ligated animals and in 19 h pylorus-ligated animals when given in divided doses. Tandamine and its structurally-related compounds, but not pirandamine or its structurally-related compound, given subcutaneously, prevented reserpine-induced gastric ulceration; imipramine was also effective. Tandamine and imipramine, administered intraperitoneally, prevented cold-restraint gastric ulceration. The compounds which block the norepinephrine, or in addition the serotonin, uptake mecahnism, but not those which block only the serotonin uptake mechanism, inhibited the gastric acid secretion and reserpine-induced ulceration. Thus, these latter activities appear to be correlated with the inhibition of the norepinephrine, rather than serotonin uptake mechanism.

Mechanism of ulcerogenic activity of reserpine in albino rats

Reserpine-induced gastric ulceration was significantly prevented by α-adrenoceptor blockers but not by propanolol or by bilateral adrenalectomy. Intracerebroventricular (i.c.v.) administration of reserpine as well as tetrabenazine failed to induce ulceration in albino rats. Pretreatment with 6-hydroxydopamine or atropine methyl nitrate protected the animals from the ulcerogenic activity of reserpine.

The effect of chronic exercise on reserpine-induced gastric ulceration in rats

The effect of chronic exercise on reserpine-induced gastric ulceration was studied in the rat. One group of male albino rats was exercised on a treadmill daily for eight weeks and then compared to a control group, not exercised but exposed to similar handling and environment. Another group swam in a tank daily for eight weeks and was compared to a control group, not exercised but exposed to similar handling and environment. The degree of ulceration of the glandular portion of the stomach produced by administration of reserpine was significantly lower in treadmill runners than in their controls, however, the degree of ulceration for the swimmers was not significantly different from that of their controls.

Bioflavonoids in Experimental Ulceration

The bioflavonoid compounds—hesperidin methyl chalcone, orange bioflavonoid complex (OBC) D-2742, OBC 291-R-1, and OBC 291-Y-1, administered alone or in combination with ascorbic acid, were evaluated for antiulcer activity according to five different procedures for producing experimental ulcers: (I) depot histamine-induced gastric ulcers in the guinea pig, (II) reserpine-induced gastric ulcers in the seven and one-half hour pylorus ligated rat, (III) thermally induced serosal burn lesions in the rat stomach, (IV) ulcers induced by fifteen-hour pylorus ligation in the rat, and (V) gastric ulceration in the rat induced by repeated injections of reserpine. The combination of OBC 291-R-1 and ascorbic acid exhibited a greater trend than either agent alone in reducing the incidence of ulceration in procedure I. OBC 291-Y-1, ascorbic acid, and combinations of these two factors reduced the incidence of ulceration in procedure II. Neither the bioflavonoid compounds nor ascorbic acid alone or in combination were effective in reducing the degree of ulceration in the other three experimental procedures.