Total Acid Output Research Articles

Investigation of a biopolymer-based pH-responsive and sustained release raft-gel-forming tablet of famotidine: In-vitro, ex-vivo, bioavailability and anti-ulcer evaluation in New Zealand albino rabbit

Famotidine (FAM), a histamine H2 receptor antagonist, routinely used for gastric ulcers. However, the poor permeability, short biological half-life and degradation in acidic gastric environment, limits its bioavailability and reduces the expression of potential bioactivity. The present study investigated sodium alginate as a pH responsive and raft-gel-forming biopolymer along with slowly releasing ingredients to achieve stomach site-specific, stable and sustained release FAM tablet (FAMRFT) for the management of gastric ulcer. The Box Behnken design was adopted to optimize raft strength and sustained release profile. The optimized FAMRFT was evaluated in terms of in-vitro, ex-vivo and in-vivo in suitable animal models. In-vitro release study showed that FAMRFT can effectively and continuously sustained-release with diffusion mechanism. Ex-vivo permeation study in porcine gastric mucosa showed two-fold increase in permeation parameters. In-vivo studies in New Zealand albino rabbits, the X-ray scintigraphy confirmed the formation of raft-gel in gastric and buoyancy, improved 3-fold bioavailability as compared to pure FAM and commercial tablet, respectively. Further, the improved gastro protective effects were reflected in gastric volume, total acid output, pH, ulcer score, ulcer index, ulcer protection and biomarkers level such as malondialdehyde (MDA), total glutathione (GSH) and nitric oxide (NO) in aspirin-induced gastric ulcers in albino rabbit. Moreover, histopathological study revealed the absence of epithelial erosion, submucosal edema and leucocytes infiltration in gastric mucosa. The results indicate that sodium alginate-based pH responsive raft-gel may be a new formulation for the application of FAM for the treatment of gastric ulcer.

EFFECT OF HYOSCIN N-BUTYL BROMIDE ON GASTRIC ULCERATION INDUCED BY INDOMETHACIN AND RESTRAINT STRESS, AND ON GASTRIC SECRETION IN ADULT MALE ALBINO RATS

Background: Hyoscine N-butylbromide (Buscopan) is clinically used as an anticholinergic antispasmodic for the treatment of abdominal cramping or visceral pain associated with cramps. Objectives: we aimed to study the effect of pretreatment by a single injection of various doses of Hyoscin N-butylbromide (HBB) (1mg/Kg, 2.5mg/Kg and 5mg/Kg), on changes in gastric contents in pyloric ligated rats receiving indomethacin in a dose of 100mg/Kg i.p, and on gastric ulcer formation induced in rats by the same dose of indomethacin and subjected to restraint stress. Materials and Methods: This study was conducted on 60 adult male albino rats, divided into two equal categories, which were further divided into five equal subgroups. Results: Administration of HBB in doses of 1mg/Kg (i.p) to rats subjected to restraint stress and indomethacin administration in a dose of 100mg/kg led to insignificant decrease in the gastric ulcer index relative to the group received indomethacin and subjected to restraint stress with a protection ratio of (3%). Administration of HBB in doses of 2.5mg/Kg and 5mg/Kg (i.p) to rats subjected to restraint stress and indomethacin administration in a dose of 100mg/kg led to a significant decrease in the gastric ulcer index relative the group received indomethacin and subjected to restraint stress with a protection ratio of 60.46% and 66.41% respectively. Administration of HBB in doses of 1mg/Kg, 2.5mg/Kg and 5mg/Kg (i.p) to pyloric-ligated rats led to a significant decrease in gastric juice volume, acid concentration and the total acid output compared to the group receiving indomethacin. Conclusion: Intraperitoneal administration of HBB in doses of 1mg/Kg, 2.5mg/Kg and 5mg/Kg to rats in a dose-dependent manner led to a prophylactic effect against stress induced gastric ulcers, with a protection ratio of 3%, 60.46% and 66.41% respectively.

Alleviation of ascorbic acid-induced gastric high acidity by calcium ascorbate in vitro and in vivo.

Ascorbic acid is one of the most well-known nutritional supplement and antioxidant found in fruits and vegetables. Calcium ascorbate has been developed to mitigate the gastric irritation caused by the acidity of ascorbic acid. The aim of this study was to compare calcium ascorbate and ascorbic acid, focusing on their antioxidant activity and effects on gastric juice pH, total acid output, and pepsin secretion in an in vivo rat model, as well as pharmacokinetic parameters. Calcium ascorbate and ascorbic acid had similar antioxidant activity. However, the gastric fluid pH was increased by calcium ascorbate, whereas total acid output was increased by ascorbic acid. In the rat pylorus ligation-induced ulcer model, calcium ascorbate increased the gastric fluid pH without changing the total acid output. Administration of calcium ascorbate to rats given a single oral dose of 100 mg/kg as ascorbic acid resulted in higher plasma concentrations than that from ascorbic acid alone. The area under the curve (AUC) values of calcium ascorbate were 1.5-fold higher than those of ascorbic acid, and the Cmax value of calcium ascorbate (91.0 ng/ml) was higher than that of ascorbic acid (74.8 ng/ml). However, their Tmax values were similar. Thus, although calcium ascorbate showed equivalent antioxidant activity to ascorbic acid, it could attenuate the gastric high acidity caused by ascorbic acid, making it suitable for consideration of use to improve the side effects of ascorbic acid. Furthermore, calcium ascorbate could be an appropriate antioxidant substrate, with increased oral bioavailability, for patients with gastrointestinal disorders.

English

Artemisia parviflora Roxb.(Asteraceae) has medicinal properties. This study evaluates the gastroprotective potential of A. parviflora seeds against aspirin induced ulcers in albino rabbits.Thirty-six rabbits were randomly divided into 6 equal groups (n = 6). Group 1 was control; group 2 received aspirin for 14 days; group 3 received omeprazole + aspirin for 14 days; groups 4, 5, and 6 received A. parviflora seed powder 250, 500, and 750 mg/kg, respectively along with aspirin, for 14 days. Total oxidant status (TOS), totalantioxidant capacity (TAC), malondialdehyde (MDA), and catalase (CAT) were determined to check the gastric damage. Ulcer score, gastric volume, gastric pH, and total acid output was also measured to determine gastroprotective potential of A. parviflora. A. parviflora seed powder exhibit gastroprotective potential with significant reduction in the ulcer score, acid output, and gastric volume while the pH of gastric mucosa increases significantly at the dose of 750 mg/kg when compared to aspirin treated group. Biochemical analysis showed a significant increase in TAC and CAT activity while it showed significant decrease in the levels of TOS and MDA which indicate reduction in gastric damage.A. parviflora seed powder proved to be gastroprotective at 250, 500 and 750 mg/kg with gastric protection of 47.5, 58.1, and 73.5%, respectively. It also has potent antioxidant properties. Key words: Antiulcer, ulcer score, gastric volume, gastric pH.

Antiulcer Study of <I>Capparis zeylanica</I> Extract on Gastric Secretions and Phenylbutazone Induced Chronic Ulceration in Experimental Animals

Purpose : The objective of the study was to investigate the possible effects of 50% ethanolic extract of Capparis zeylanica (CZE) on gastric secretion and Phenylbutazone ulcer in rats. Approach : Twenty four adult male rats were used in this study (four groups) and several parameters were determined to assess any degree of protection. The ulceration was induced by Phenylbutazone at a dose of 100 mg/kg b.w. Findings : Phenylbutazone toxicity induced + CZE treated rats showed a significant decrease (p > 0.001) in volume of gastric juice, free and total acidity, pepsin concentration and acid output with a significant increase (p > 0.001) in pH compared to Phenylbutazone toxicity induced rats. Phenylbutazone caused a significant decrease (p > 0.001) in TC:P with a concomitant increase (p > 0.001) in protein and DNA. After treatment of CZE in rats, a significant increase (p > 0.001) in the carbohydrate concentration in terms of TC:P ratio and significantly lowered (p > 0.001) protein concentration in gastric juice was observed. CZE tended to increase mucin activity in Phenylbutazone + CZE group. Conclusion : It can be concluded that CZE imparted a protective action against phenylbutazone induced chronic ulcer in rats.

Ulcer Protective Activity of Jatropha gossypiifolia Linn. in Wistar Rats.

Background:Several synthetic drugs are useful in the treatment of peptic ulcer, but almost of these drugs are used in prolonging time, it may cause several adverse reactions. However, the herbal medicines are more potent to the treatment and minimize the side effects.Objective:To evaluate the methanol extract of Jatropha gossypiifolia Linn. (MEJG) for gastro protective activity against Wistar rats.Materials and Methods:Anti-ulcer potency of MEJG (100 and 200 mg/kg, b.w.) was assessed using aspirin (200 mg/kg, p.o.) plus pylorus ligation ulcer model and the parameters studied were ulcer index (UI), gastric juice volume, pH, total acidity, and total acid output. Same extract was studied by ethanol-induced (80%, 5 mL/kg, intragastrically) ulcer model, and the UI and biochemical parameters were studied.Results:The oral administration of MEJG (100 and 200 mg/kg) significantly (P < 0.001) attenuated the ulcer score and anti-secretary parameters (such as the volume of gastric content, free acidity, total acidity, and total acid output) in the aspirin plus pylorus ligation rats. The extract also significantly attenuated (P < 0.001) ulcer score in ethanol-induced ulcer model and lipid peroxidation level and significantly increased the level of glutathione peroxides, catalase, and superoxide dismutase activity. The MEJG may possess active constituents such as alkaloids, glycosides, flavonoids, and terpenes, which may play a major role in gastroprotective effect in Wistar rats.Conclusion:The present study provides scientific support for the anti-ulcer activities of extracts of JG and also claimed that antioxidant potential of the extracts. However, substantiates the traditional claims for the usage of this drug in the treatment of gastric ulcer.SUMMARY The methanolic extract of jatropha gossypiifolia Linn. for gastro protective activity against aspirin plus pyloric ligation and ethanol induced ulcer models was studied in Wistar rats. JG shows significantly attenuated the ulcer score in both models. And also attenuated in anti-secretory parameters in aspirin induced ulcer model. MEJG may possess active constituents such as alkaloids, glycosides, flavonoids and terpenes, which may play a major role in gastroprotective effect in Wistar rats. Abbreviation Used: MEJG: Methanolic extract of jatropha gossypiifolia, mg: Milli gram, kg: Kilogram, b.w.: Body weight, p.o.: Per oral, UI: Ulcer index, pH: Concentration of H+ ion, mL: Milli litre, JG: Jatropha gossypiifolia,USD: United States Dollar, NSAIDs: Non steroidal anti-inflammatory drugs, v/v: Volume by volume, w/v: Weight by volume, SCMC: Sodium carboxy methyl cellulose, g: Gram, h: Hour, °C: Degree centigrade, n: Number, Rpm: Rotation per minute, Min: Minute, N: Normality, NaoH: Sodium hydroxide, mM - Millimole, TBA: Thiobarbituric acid, nmol: Nanomole, nm: Nanometer, GPx: Glutathione peroxidase, GSH: Reduced glutathione, H2O2: Hydrogen peroxide, SOD: Superoxide dismutase, ANOVA: Analysis of Variance, μmol: Micromole

Effect of midazolam on gastric secretion and stress-induced gastric ulceration in male albino rats

The term ‘benzodiazepine’ refers to a distinct chemical structure. Benzodiazepines are now used for testing acute anxiety states, and also as a premedication before surgery. Although diazepam is the prototype of benzodiazepine, midazolam is more potent. As peptic ulcers are now being diagnosed more often in school children, and because preanaesthetic management is difficult for children, the use of preoperative sedatives may help to diminish anxiety, minimize psychological trauma and improve the quality of anaesthesia. Midazolam is often used as a preoperative sedative, and during procedures such as endoscopy, where anaesthesia is not required. There is no available data about the effect of various doses of midazolam on gastric secretion and on restraint-induced gastric ulcers in rats. Therefore, the aim of the present study was to study the effect of 0.5, 1 and 2.5 mg/kg of midazolam on gastric secretion and on immobilization-induced gastric stress ulcers in rats. This study was conducted on 48 rats, divided into two big categories, each consisting of 24 rats, which were further divided into four groups, each group consisting of six rats. Administration of midazolam in doses of 0.5 and 1 mg/kg intraperitoneal to pyloric-ligated rats led to a significant decrease in gastric juice volume, acid concentration and the total acid output compared with the control group, which received normal saline. Midazolam administration in a dose of 2.5 mg/kg led to a significant increase in the gastric juice volume, and a significant decrease in the acid concentration and the total acid output compared with the control group. Our results concluded that midazolam administration in a dose of 0.5 mg/kg to children as a prophylactic dose during preanaesthetic medication leads to prevention of aspiration pneumonia, morbidity and mortality of children during endoscopies and elective surgical operations. Restraint-induced stress ulcers approach the ideal technique for ulcer production and testing of antiulcer agents. Our results showed that intraperitoneal administration of midazolam in doses of 0.5, 1 and 2.5 mg/kg to rats in a dose-dependent manner leads to a prophylactic effect against stress-induced gastric ulcers with a protection index of 9.4, 23.8 and 32.2%, respectively. The mechanism of prophylaxis is due to its sedative, anxiolytic and antisecretory effect.

Comparative investigation into the anti-ulcer activity of virgin coconut oil and coconut oil in pylorous ligated animal model

This current study investigated the anti-ulcer activity of 2 types of virgin coconut oil (VCO-A and VCO-B) and coconut oil (CO). Sprague-Dawley of male rats divided into 6 groups and each group consisted of ten rats. Rats were then treated with either VCO or CO and then were then anaesthetized and pyloric ligation was performed. The anaesthesia was discontinued and the animal usually recovered consciousness within less than an hour. Three hours later, the animal was then again anaesthetized and sacrificed with chloroform. Stomach removed and its content subjected to measurement of volume and pH. The results revealed VCO-B and VCO-A(100%) significantly inhibited (< 0.001) the volume of gastric juice secreted by the control rats by 66.81% and 51.53%, respectively. Followed by CO 42.80%. While the inhibition of gastric juice for positive control rates which treated with ranitidine (100 mg/kg) was only 22.38%. The total acid output was reduced by the oils to 70.80%, 74.16% and 40.45% for VCO-A, VCOB and CO respectively compared to control group. Ranitidine reduced the total acid output by 34.83%. In conclusion, prevention of gastric lesions in rats by VCO was found to increase the mucous and decrease the acid volume, total acid contents and ulcer scoring. The treatment of VCO affects the all parameters that influence the initiation and perpetuation of ulceration.

NESFATIN-1 TREATMENT ALLEVIATES INDOMETHACIN-INDUCED GASTRIC ULCER IN RATS

Background: Indomethacin is a non-steroidal anti-inflammatory drug which is known to produce serious adverse effects including ulcerative lesions. Nesfatin-1, is an identified anorexigenic peptide to have antioxidant effects. Objective: This study aimed to investigate the possible ameliorative effect of nesfatin-1 against indomethacin induced gastric ulcer in rats, with exploration of the possible mechanisms underlying this effect. Materials and methods: Twenty four adult male albino rats were the animal model of this study. Ulcers were induced using oral indomethacin (20mg/kg) daily for 7 days. The rats were randomly assigned to vehicle-treated control group (I), indomethacin-treated (II), and indomethacin-treated for 7 days followed by nesfatin-1 (1ug/kg i.p) daily for 10 days. Assessment of gastric juice parameters (total acid output, pepsin activity and mucin content),gastric mucosal levels of malondialdehyde (MDA) , tumor necrosis factor –alpha (TNF-alpha) , nitrite and prostaglandin E2 (PGE2) levels were also determined. This in addition to assessment of gastric lesions and histopathologic examination of the gastric mucosa in each group. Results: Nesfatin-1 displayed a significant ameliorative effect in gastric lesions induced by indomethacin as indicated by a significant decrease in ulcer index and improved histopathology, along with a significant reduction in measured gastric juice parameters .It also reduced both gastric mucosal MDA and TNF-alpha significantly and increased nitrite and PGE2 levels in this ulcer model. Conclusion: Nesfatin-1 attenuates indomethacin- induced gastric ulcer and potentiates ulcer healing in the stomach of rats exposed to chronic administration of indomethacin. This effect depended upon decrease in gastric secretion, increase in nitric oxide and PGE2, besides an antioxidant anti-inflammatory role.

Protective Effect of Liriodendrin Isolated from Kalopanax pictus against Gastric Injury

In this study, we investigated the inhibitory activities on gastritis and gastric ulcer using liriodendrin which is a constituent isolated from Kalopanax pictus. To elucidate its abilities to prevent gastric injury, we measured the quantity of prostaglandin E2 (PGE2) as the protective factor, and we assessed inhibition of activities related to excessive gastric acid be notorious for aggressive factor and inhibition of Helicobacter pylori (H. pylori) colonization known as a cause of chronic gastritis, gastric ulcer, and gastric cancer. Liriodendrin exhibited higher PGE2 level than rebamipide used as a positive control group at the dose of 500 μM. It was also exhibited acid-neutralizing capacity (10.3%) and H+/K+-ATPase inhibition of 42.6% (500 μM). In pylorus-ligated rats, liriodendrin showed lower volume of gastric juice (4.38 ± 2.14 ml), slightly higher pH (1.53 ± 0.41), and smaller total acid output (0.47 ± 0.3 mEq/4 hrs) than the control group. Furthermore liriodendrin inhibited colonization of H. pylori effectively. In vivo test, liriodendrin significantly inhibited both of HCl/EtOH-induced gastritis (46.9 %) and indomethacin-induced gastric ulcer (46.1%). From these results, we suggest that liriodendrin could be utilized for the treatment and/or protection of gastritis and gastric ulcer.

GASTRO PROTECTIVE AND ANTIOXIDANT EFFECT OF EUPHORBIA PROSTRATA AGAINST INDOMETHACIN INDUCED GASTRIC ULCERS IN HEALTHY ADULT MALE ALBINO RABBITS

Euphorbia prostrate belongs to family Euphorbiaceae locally known as Doodhi is small annual herb. Current study was conducted t o evaluate the gastro protec tive and antioxidant effectiveness of the aerial parts of E . prostrata in indomethacin induced ulcer in adult male albino rabbits. A total 36 mice were taken and divided into 6 equal groups . At day 0 and 14 of experiment the blood sample was collected from each animal and serum was separated from blood which was used for the determination of Total oxidant status (TOS) , Total antioxidant capacity (TAC) , catalase (CAT) and Malondialdehyde (MDA) . At the end of the experiment, all of the rabbits were slaughtere d . The gastric content s were collected to total acid output , gastric pH and gastric volume . To confirm the data results was subjected to one way analysis of variance (ANOVA). Results when compared with the extensive mucosal damage in the indomethacin trate d group , gross evaluation revealed a marked protection of the gastric mucosa in the experimental groups, with significantly reductio n in gastric pH, gastric volume and acid output. In these groups, CAT and TAC levels were significantly increased (P < 0.05) and while MDA and TOS significantly reduced (P < 0.05) which indicate reduction in gastric damage. In conclusion to these results E. prostrata has potent antioxidant properties at dose rate of 240 mg/kg and it is also very effective for the treatment of g astric ulcer at the same dose.

Gastroprotective activity of reconstituted red fruit pulp concentrate of Citrullus lanatus in rats.

Aim:This study was carried out to evaluate the gastroprotective potential of the aqueous fruit pulp concentrate of Citrullus lanatus citroides (CLC) on pyloric ligation and indomethacin-induced ulcer in Wistar albino rats.Materials and methods:In indomethacin-induced ulcer model, CLC was administered in the doses of 250 mg/kg, 500 mg/kg and 1000 mg/kg body weight orally, tds for 5 days. The antiulcer activity was determined via observing reduction in ulcer index whereas in the pyloric ligation model, the gastroprotective effect of CLC was assessed from the alteration in volume of gastric juice, pH, free and total acidity, protein concentration in gastric juice. Further lipid peroxide (LPO), and activities of enzymic antioxidants such as superoxide dismutase (SOD) and catalase (CAT) was also determined along with the levels of hexose, hexosamine, sialic acid, fucose in gastric mucosa.Results:In both models, treatment with CLC caused a significant reduction in lesion index when compared to vehicle treated group, providing evidence for antiulcer capacity. In pyloric ligation model, pretreatment with CLC resulted in significant increase in pH, enzymic antioxidants, that is, SOD, CAT, with a significant decrease in volume of gastric juice, free and total acidity, protein concentration, acid output, and LPO levels respectively. The presence of the flavonoids and polyphenols may be responsible for the gastroprotective effect of CLC.Conclusions:The aqueous fruit pulp concentrate of CLC showed significant gastroprotective potential against pyloric ligation and indomethacin-induced ulceration in rats.

Protective effect of hydrogen sulfide against cold restraint stress-induced gastric mucosal injury in rats

Hydrogen sulfide (H2S) is an endogenous gaseous mediator plays a potential role in modulating gastric inflammatory responses. However, its putative protective role remains to be defined. The present study aimed to evaluate role of the exogenously released and endogenously synthesized H2S in cold restraint stress (CRS)-induced oxidative gastric damage in rats. Rats were restrained, and maintained at 4°C for 3h. The H2S donor, sodium hydrosulfide (NaHS) (60μmol/kg) was injected intraperitoneally (i.p.) before CRS. Our results revealed that NaHS pretreatment significantly attenuated ulcer index, free and total acid output, and pepsin activity in gastric juice along with decreased gastric mucosal carbonyl content and reactive oxygen species production. This was accompanied by increased gastric juice pH and mucin concentration in addition to restoring the deficits in the gastric reduced glutathione, catalase as well as superoxide dismutase enzyme activities. NaHS pretreatment markedly reduced the serum level of tumor necrosis factor (TNF-α) and myeloperoxidase activity compared to CRS-non-treated. Moreover, NaHS preadministration significantly abrogated the inflammatory and the deleterious responses of gastric mucosa in CRS. The protective effects of H2S were confirmed by gastric histopathological examination. However, pretreatment with the H2S-synthesizing enzyme, cystathionine-gamma-lyase inhibitor, beta-cyano-L-alanine (50mg/kg, i.p.) reversed the gastroprotection afforded by the endogenous H2S. Collectively, our results suggest that H2S can protect rat gastric mucosa against CRS-induced gastric ulceration possibly through mechanisms that involve anti-oxidant and anti-inflammatory actions alongside enhancement of gastric mucosal barrier and reduction in acid secretory parameters.

Mechanisms of the Protective Effects of Curcumin against Indomethacin-Induced Gastric Ulcer in Rats

Background/Aims: Curcumin, a naturally occurring polyphenolic compound, exhibits anti-inflammatory and antioxidant properties that render it an attractive candidate for protection against gastric ulcer. The aim of this study is therefore to evaluate the protective effects of curcumin against indomethacin-induced gastric ulcer in rats. Methods: Gastric ulceration was induced by a single intraperitoneal injection of indomethacin (30 mg/kg). Curcumin (50 mg/kg, p.o.) was administered 30 min before ulcer induction. Results: Curcumin showed gastroprotective effects as evidenced by significant decreases in ulcer index, total acid output and pepsin activity in gastric juice in addition to gastric mucosal malondialdehyde concentration, and concomitant increases in gastric juice mucin concentration, gastric mucosal nitric oxide level and catalase and superoxide dismutase activities as compared to the indomethacin-induced ulcer group. Moreover, immunohistochemical investigations demonstrated that curcumin treatment markedly decreased expression of inducible nitric oxide synthase, nuclear factor-κB, and caspase-3. Conclusion: Curcumin protected the rats' gastric mucosa against indomethacin-induced gastric ulceration possibly, at least in part, by enhancement of the gastric mucosal barrier and reduction in acid secretory parameters in addition to antioxidant and antiapoptotic activities.

Gastric acid secretion in experimental acute uremia

This study was conducted to evaluate gastric acid secretion in acute renal failure, highlighting the roles of renal mass and gastrin hormone. Acute uremic rats were divided into bilateral nephrectomized and bilateral ureteric obstruction groups. Gastric juice was collected for 2 h and analyzed for volume, free acidity, total acidity, and total acid output. Plasma levels of creatinine, urea, and gastrin were also determined. Bilateral nephrectomized and bilateral ureteric obstruction groups showed a significant increase in levels of free acidity, total acidity, and plasma gastrin. Compared with the ureteric obstruction group, nephrectomized rats showed a significant increase in gastric juice volume, total acid output, and plasma gastrin levels. Following pentagastrin stimulation, gastric juice volume, total acid output, free acidity, and total acidity were increased in the bilateral nephrectomy and ureteric obstruction groups compared with the respective control groups. The free and total acidity and total acid output also increased compared with the respective non-stimulated groups. Plasma creatinine and urea levels were significantly positively correlated with plasma gastrin, free acidity, and total acidity. Creatinine was positively correlated with total acid output, and gastrin was positively correlated with total acidity. In conclusion, acute renal failure promotes gastric acid hypersecretion that could potentially be attributed to high levels of gastrin hormone and uremic state per se.

Role of plant stanol derivatives in the modulation of cholesterol metabolism and liver gene expression in mice

The present study was to evaluate the cholesterol-lowering effect of two novel plant stanol derivatives and its potential molecular mechanism in hyper-cholesterol mice induced by a high-cholesterol diet. Results showed that oral administration of plant stanyl hemisuccinate (2×, 5×) and plant stanyl sorbitol succinate (2×, 5×) effectively attenuated the serum total cholesterol and low density lipoprotein cholesterol levels, while had no effect on the serum triacylglycerol and high density lipoprotein cholesterol. And plant stanol derivatives decreased liver cholesterol concentration and increased faecal cholesterol output. Meanwhile, both plant stanyl hemisuccinate and plant stanyl sorbitol succinate could remarkably promote liver X receptor alpha (LXRα) expression, and increased cholesterol 7α-hydroxylase (CYP7A1) expression and faecal total bile acid output to varying degrees. These results suggested two novel plant stanol derivatives possessed hypocholesterolemic effect, and the cholesterol-lowering action of plant stanol derivatives may be through activating the potential LXRα-CYP7A1-bile acid excretion pathway.

Gastroprotective effect of Desmodium gangeticum roots on gastric ulcer mouse models

In the present study, the ethanolic root extract of Desmodium gangeticum (L.) DC., Fabaceae, (EDG), have been studied in various acute and chronic ulcer mouse models. Oral administration of root extract, significantly decrease the ulcer index and lesion number in a dose dependent manner against ethanol induced acute gastric ulcer in mice. In gastric ulcerated animal that received high dose of 150 mg/kg EDG, the mucosa showed no ulceration with slight focal congestion and the glands appeared normal. Pylorus ligated mice, pretreated with EDG showed significant decrease in ulcerous activity under chronic condition. The highest dose (150 mg/kg) of the extract provoked a marked increase in protein and glutathione levels, when compare to control. Furthermore, gastric juice, free acidity and total acid output were inhibited in a dose-dependent manner at p<0.05 level. Our results indicate that the EDG possess gastroprotective activity and increasing regeneration of damaged gastric mucosa and thus safe for human use.

Lateral hypothalamic area mediated the protective effects of microinjection of glutamate into interpositus nucleus on gastric ischemia-reperfusion injury in rats

We investigated the protective effects of chemical stimulation of cerebellar interpositus nucleus (IN) on gastric ischemia-reperfusion injury (GI-RI) and its possible regulatory mechanisms in rats. Gastric mucosal damage index (GMDI) indicated the severity of gastric mucosal injuries. Transferase dUTP nick end labeling (TUNEL) staining and proliferating cell nuclear antigen (PCNA) were performed to assess gastric mucosal cell apoptosis and proliferation. Microinjection of glutamate into IN markedly attenuated GI-RI. Either chemical lesion of IN or electrical ablation of the decussation of superior cerebellar peduncle (DSCP) obviously aggravated GI-RI. The protective effects of IN were reversed with the pretreatments of microinjection of 3-mercaptopropionic acid into IN or Bicuculline into lateral hypothalamic area (LHA), individually. The discharge frequency and intensity of greater splanchnic nerve (GSN) decreased and gastric mucosal blood flow increased after chemical stimulation of IN. The apoptosis of positive cells of gastric mucosa was decreased by chemical stimulation of IN, whereas proliferation increased. The gastric juice volume, acidity, and total acid output were all decreased after the chemical stimulation of IN. These results indicated that IN participates in regulation of GI-RI and is a specific area in central nervous system for exerting protective effects on GI-RI. DSCP, LHA and GSN may involve in this process. Apoptosis and proliferation may mediate this protective process in rats too.

Protective effects of nebivolol against cold restraint stress-induced gastric ulcer in rats: Role of NO, HO-1, and COX-1,2

Nebivolol, a β1-adrenoceptor antagonist, exhibits vasodilatory and anti-oxidative properties that rendering it attractive candidate for protecting against gastric ulcer. The aim of this study therefore is to evaluate the protective effects of nebivolol against cold restraint stress (CRS)-induced gastric ulcer in rats. Rats were restrained, and maintained at 4°C for 3h. Nebivolol (5mg/kg, p.o.) was suspended in 0.5% aqueous solution of carboxymethyl cellulose and was administered 30min before CRS. Nebivolol exhibited gastroprotective effects as evidenced by significant decreases in ulcer index as well as free and total acid output, and pepsin activity in gastric juice in addition to gastric mucosal malondialdehyde concentration, with concomitant increases in gastric juice pH and mucin concentration along with gastric mucosal reduced glutathione and nitric oxide (NO) concentrations compared with CRS rats. Moreover, immunohistochemical analysis demonstrated that nebivolol treatment markedly enhanced heme oxygenase-1 as well as cyclooxygenase-1 and cyclooxygenase-2 expressions. The protective effects of nebivolol were confirmed by gastric histopathological examination. Pretreatment with Nω-nitro-l-arginine, a NO synthase inhibitor, partly altered the protection afforded by nebivolol. In conclusion, nebivolol protected rats’ gastric mucosa against CRS-induced gastric ulceration possibly through anti-oxidant activity, enhancement of gastric mucosal barrier and reduction in acid secretory parameters.

Study on hepatotoxicity of aqueous extracts of Polygonum multiflorum in rats after 28-day oral administration-analysis on correlation of cholestasis

To observe the liver injury degree of SD rats after 28-day administration of aqueous extracts of Polygonum multiflorum (AEPM) and the correlation with cholestasis mechanism. Adult SD rats were orally administered with 30, 60 g x kg(-1) of APEM once every day for 28 d. After 28 d, the general condition of rats such as weight were observed, liver function-related indicators were detected. Bile was collected to determine total bile acid output, flow rate and density and changes in major compositions. Their livers were weighed then sent for histopathological examination. AEPM did not change the general conditions and weights of rats. From the results of the related indicators of liver function and cholestasis, AEPM did not change the contents of ALT and AST in serum, but high dose of AEPM can increase the contents of ALP, GGT and TBA in serum (P < 0.05, P < 0.01) and decrease the content of TBIL in serum (P < 0.05). And the contents of GGT in serum of low dose rats were increased (P < 0.05). The bile flow was not changed by AEPM, but bile compositions of high dose male rats were obviously changed (TG increase, TBIL decrease, TBA decrease). The weights of liver and ratio of liver of the high dose rats were increased but showed no statistical significance. Pathologic examination displayed that there were only small pieces of necrosis in livers of several rats, without any severe disease. AEPM can obviously injure bile duct epithelial cells, intervene liver cell functions and change bile compositions in rats, thus it is proved to induce cholestasis without severe liver injury.