Protective effect of lysozyme chloride on gastric oxidative stress and hemorrhagic ulcers in severe atherosclerotic rats.

BACKGROUND: Calcium and cholesterol play major roles in the formation of atherosclerosis. Whether severe atherosclerosis induced by co-administration of a mixture containing vitamin D2 (vit D2) and cholesterol can result in gastric hemorrhagic damage is unknown. Gastric oxidative stress and hemorrhagic ulceration in rats with atherosclerosis induced by co-administration of vit D2 and cholesterol and the protective effect of lysozyme chloride on this ulcer model were investigated. MATERIAL/METHODS: Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vit D2 and cholesterol to induce atherosclerosis. Control rats received the same volume of corn oil only. After 24-h fasting followed by gastric surgery, the rat stomachs were irrigated for 3 h with simulated rat gastric juice or normal saline. Various gastric mucosal ulcerogenic factors (acid back-diffusion, lipid peroxides, histamine concentration, and hemorrhagic ulcers) and defensive substances (mucosal glutathione and mucus secretion) were determined. RESULTS: Augmentation of serum calcium concentration, total cholesterol, and low-density lipoprotein was observed in atherosclerotic rats. Greater mucosal ulcerogenic parameters and lower defensive substances were achieved in these rats. High correlation between decreased mucosal glutathione and ulceration as well as between increased mucosal lipid peroxide levels and ulceration was also found in the atherosclerotic rats. Daily intragastric lysozyme chloride dose-dependently protected gastric mucosal hemorrhagic damage in the atherosclerotic rats. CONCLUSIONS: Atherosclerosis induced by co-administration of vit D2 and cholesterol could produce gastric oxidative stress and hemorrhagic ulcer that was ameliorated by lysozyme chloride in rats.

Protective effect of verapamil on gastric hemorrhagic ulcers in severe atherosclerotic rats.

Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.

Effect of taurine on gastric oxidative stress and hemorrhagic erosion in brain ischemic rats.

The effect of taurine on gastric hemorrhage and mucosal erosion in the brain ischemia (BI) is unknown. The aim of the research was to study the involvement of gastric oxidative stress in hemorrhagic erosion produced in BI rats. The protective effect of taurine on this erosion model was evaluated. Male Wistar rats were deprived of food for 24 h. Under chloral hydrate -anesthesia, bilateral carotid artery ligation (BCAL) was performed 12, 18 and 21 h after removal of food to obtain 12, 6 and 3 h of BI duration. The pylorus and carotid esophagus of rats also were ligated. The stomachs were then irrigated for 3 h with normal saline or simulated gastric juice containing 100 mM HCl plus 17.4 mM pepsin and 54 mM NaCl. The stomach was dissected. Gastric samples were harvested. The rat brain was dissected for examination of ischemia by using triphenyltetrazolium chloride staining method. Changes in gastric ulcerogenic parameters, such as decreased mucosal GSH level as well as enhanced gastric acid back-diffusion, mucosal lipid peroxide generation, histamine concentration, luminal hemoglobin content and mucosal erosion in gastric samples were measured. The results indicated that BCAL could produce severe BI in rats. Moreover, a BI- duration-dependent exacerbation of various ulcerogenic parameters also was observed in these rats. Intraperitoneal taurine (0-300 mg/kg) dose-dependently ameliorated gastric oxidative stress and hemorrhagic erosion in BI rats. Taken together, BI could produce gastric oxidative stress and hemorrhagic erosions that was ameliorated by taurine through stimulation of GSH biosynthesis and inhibition of oxidative stress.

Role of gastric oxidative stress and nitric oxide in formation of hemorrhagic erosion in rats with ischemic brain.

AIM: To investigate the role of gastric oxidative stress and nitric oxide (NO) in the formation of gastric hemorrhagic erosion and their protection by drugs in rats with ischemic brain. METHODS: Male Wistar rats were deprived of food for 24 h. Under chloral hydrate (300 mg/kg) anesthesia, bilateral carotid artery ligation was performed. The pylorus and carotid esophagus of the rats were also ligated. The stomachs were then irrigated for 3 h with either normal saline or simulated gastric juice containing 100 mmol/L HCl plus 17.4 mmol/L pepsin and 54 mmol/L NaCl. Rats were killed and stomachs were dissected. Gastric mucosa and gastric contents were harvested. The rat brain was dissected for the examination of ischemia by triphenyltetrazolium chloride staining method. Changes in gastric ulcerogenic parameters, such as decreased mucosal glutathione level as well as enhanced gastric acid back-diffusion, mucosal lipid peroxide generation, histamine concentration, luminal hemoglobin content and mucosal erosion in gastric samples, were measured. RESULTS: Bilateral carotid artery ligation produced severe brain ischemia (BI) in rats. An exacerbation of various ulcerogenic parameters and mucosal hemorrhagic erosions were observed in these rats. The exacerbated ulcerogenic parameters were significantly (P<0.05) attenuated by antioxidants, such as exogenous glutathione and allopurinol. These gastric parameters were also improved by intraperitoneal aminoguanidine (100mg/kg) but were aggravated by N(G)-nitro-L-arginine-methyl ester (L-NAME: 25 mg/kg). Intraperitoneal L-arginine (0-500 mg/kg) dose-dependently attenuated BI-induced aggravation of ulcerogenic parameters and hemorrhagic erosions that were reversed by L-NAME. CONCLUSION: BI could produce hemorrhagic erosions through gastric oxidative stress and activation of arginine-nitric oxide pathway.

Effect of lysozyme chloride on betel quid chewing aggravated gastric oxidative stress and hemorrhagic ulcer in diabetic rats.

AIM: To evaluate the protective effect of lysozyme chloride on betel quid chewing (BQC) aggravated gastric oxidative stress and hemorrhagic ulcer in rats with diabetes mellitus (DM). METHODS: Male Wistar rats were challenged intravenously with streptozotocin (65 mg/kg) to induce DM. Rats were fed with regular pellet food or BQC-containing diets. After 90 d, rats were deprived of food for 24 h. Rat stomachs were irrigated for 3 h with normal saline or simulated gastric juice. Rats were killed and gastric specimens were harvested. RESULTS: An enhancement of various gastric ulcerogenic parameters, including acid back-diffusion, mucosal lipid peroxide generation, as well as decreased glutathione levels and mucus content, were observed in DM rats. After feeding DM rats with BQC, an exacerbation of these ulcero-genic parameters was achieved. Gastric juice caused a further aggravation of these ulcerogenic parameters. Daily intragastric lysozyme chloride dose-dependently inhibited exacerbation of various ulcerogenic parameters in those BQC-fed DM rats. CONCLUSION: (1) Gastric juice could aggravate both DM and BQC-fed DM rat hemorrhagic ulcer; (2) BQC exacerbated gastric hemorrhagic ulcer in DM rats via enhancing oxidative stress and reducing defensive factors; (3) lysozyme chloride effectively protected BQC aggravated gastric damage in DM rats.

Modulation of gastric hemorrhage and ulceration by oxidative stress and histamine release in Salmonella typhimurium-infected rats.

Infection with Salmonella typhimurium can produce multiple organ dysfunctions. However, document concerning with gastric hemorrhagic ulcers occur in this infectious disease is lacking. The aim was to study modulation of gastric hemorrhagic ulcer by oxidative stress and mast cell histamine in S. typhimurium-infected rats. Additionally, the protective effects of drugs, such as ofloxacin, lysozyme chloride, ketotifen, ranitidine, and several antioxidants, including exogenous glutathione (GSH), allopurinol and dimethylsulfoxide (DMSO) were evaluated. Male Wistar rats were injected intrajejunally with a live culture of S. typhimurium (1 x 10(10) colony-forming units/rat) and followed by deprivation of food for 36 h. Age-matched control rats received sterilized vehicle only. Rat stomachs were irrigated for 3 h with either normal saline or a simulated gastric juice containing 100 mM HCl, 17.4 mM pepsin and 54 mM NaCl. S. typhimurium caused aggravation of offensive factors, including enhancing gastric acid back-diffusion, mucosal lipid peroxide generation, histamine release, microvascular permeability and hemorrhagic ulcer, as well as an attenuation of defensive substances, such as mucosal GSH and mucus level. Intragastric irrigation of gastric juice caused further aggravation of these gastric biochemical parameters. This exacerbation of ulcerogenic factors was abolished by pretreatment of ofloxacin and lysozyme chloride. Antioxidants, such as reduced GSH, allopurinol and DMSO also produced significant (P < 0.05) amelioration of gastric damage in S. typhimurium infected rats. In conclusion, gastric oxidative stress and histamine play pivotal roles in the formation of hemorrhagic ulcers that were effectively ameliorated by ofloxacin, lysozyme chloride, ketotifen, ranitidine, diamine oxidase and various antioxidants in S. typhimurium-infected rats.

Role of histamine and acid back-diffusion in modulation of gastric microvascular permeability and haemorrhagic ulcers in betel-quid-fed rats.

Evidence concerning the pathogenesis of gastric haemorrhagic ulcer produced by betel quid chewing (BQC) is lacking. This research first proposes that alterations of mast cell histamine release and gastric acid back-diffusion are important in modulating gastric microvascular permeability and mucosal haemorrhagic ulcer in BQC-fed rats. The effects of several histamine receptor antagonists on this ulcer model also were evaluated. Male Wistar rats were fed with BQC diet or normal pellet diet. After 1, 30 and 90 day(s), rat stomachs were irrigated for 3 h with either normal saline or simulated gastric juice. Gastric acid back-diffusion, mucosal histamine concentration, microvascular permeability, as well as luminal haemoglobin content and ulcer areas were determined. Severe gastric haemorrhage and mucosal ulcerations, particularly in acidic stomachs, were observed in BQC-fed rats. A high correlation was observed between histamine and gastric haemorrhage, as well as between acid back-diffusion and mucosal ulceration was found in rats fed with BQC. This haemorrhagic ulcer in BQC-fed rats was effectively ameliorated by intragastric ketotifen, ranitidine or their combination. In conclusion, enhancement of acid back-diffusion, mast cell histamine release and microvascular permeability is important in modulating gastric haemorrhage and ulcer in BQC-fed rats.

Protective effects of lysozyme chloride and reduced glutathione on betel quid chewing-produced gastric oxidative stress and haemorrhagic ulcer in rats.

The pathogenic mechanisms underlying betel quid chewing (BQC)-induced gastric haemorrhagic ulcer are totally unknown. This study first demonstrated that BQC produced gastric haemorrhagic ulcer via oxidative stress that could be protected by lysozyme chloride and glutathione in rats. Male Wistar rats were fed with regular pellet food or BQC-containing diets. After 1-90 days rats were deprived of food for 24 h. Rat stomachs were irrigated for 3 h with normal saline or simulated gastric juice. Rats were killed and gastric specimens were harvested. A BQC-feeding period-dependent exacerbation of gastric parameters, such as enhanced acid back-diffusion, mucosal lipid peroxide generation, as well as related decreased glutathione levels and mucus content, were observed. Gastric juice caused a further aggravation of these ulcerogenic parameters. Daily intragastric lysozyme chloride or glutathione dose-dependently inhibited exacerbation of various ulcerogenic parameters in those BQC-fed rats. In conclusion, BQC can produce gastric haemorrhagic ulcer in rats via oxidative stress that could be ameliorated by lysozyme chloride and glutathione.

Gastric oxidative stress and hemorrhagic ulcer in Salmonella typhimurium-infected rats.

Infection of Salmonella typhimurium (Salmonella typhi) can lead to various organ diseases. This research first proposed that Salmonella typhi-infection could result in gastric oxidative stress and hemorrhagic ulcers that were ameliorated by ofloxacin, lysozyme chloride and several antioxidants, including exogenous glutathione (GSH), allopurinol and dimethylsulfoxide (DMSO). Male Wistar rats were given intrajejunally the live culture of Salmonella typhi [1 x 10(10) colony-forming unit (CFU)/rat] and followed by deprivation of food for 36 h. Age-matched control rats received vehicle only. Rat stomachs were irrigated for 3 h with either normal saline or a simulated gastric juice containing 100 mM HCl, 17.4 mM pepsin and 54 mM NaCl. Infection of Salmonella typhi produced an aggravation of ulcerogenic factors, including enhancing gastric acid back-diffusion, mucosal lipid peroxide generation and hemorrhagic ulcer as well as an attenuation of mucosal GSH level. Intragastric irrigation of gastric juice caused further aggravation of these gastric biochemical parameters. This exacerbation of ulcerogenic factors was abolished by pretreatment of ofloxacin and lysozyme chloride. Antioxidants, such as reduced GSH, allopurinol and DMSO also produced significant (P<0.05) amelioration of gastric damage in Salmonella typhi-infected rats. In conclusion, infection of Salmonella typhi substantially caused gastric oxidative stress and disruption of gastric mucosal barriers, consequently resulted in gastric hemorrhagic ulcerations that were effectively ameliorated by ofloxacin, lysozyme chloride and various antioxidants.

Role of histamine and acid back-diffusion in modulation of gastric microvascular permeability and hemorrhagic ulcers in Salmonella typhimurium-infected rats.

Documentation concerning the pathogenesis of gastric hemorrhagic ulcer in Salmonella typhimurium (Salmonella typhi)-infective disease is lacking. This research first proposed that alterations of mast cell histamine release, gastric acid back-diffusion and mucosal microvascular permeability are important in modulating gastric ulcer and hemorrhage in Salmonella typhi-infected rats. Additionally, effects of several histamine-related drugs on this ulcer model were evaluated. Male Wistar rats were deprived food for 36 h. Live cultures of Salmonella typhi (OU 5045, 1 x 10(10) CFU in 1.0 mL of sterilized phosphate buffer saline) were challenged, intrajejunally to rats just before withdrawal of food. Control rats received the same volume of sterilized vehicle only. Rat stomachs were irrigated for 3 h with either normal saline or simulated gastric juice. Gastric acid back-diffusion, mucosal histamine concentration, microvascular permeability as well as luminal hemoglobin content and ulcer areas were determined. Severe gastric hemorrhage and mucosal ulcerations, particularly in acidic stomachs, were observed in Salmonella typhi-infected rats. A positive correlation of histamine to gastric hemorrhage and ulcer was found in those rats with Salmonella typhi-infection. This hemorrhagic ulcer in Salmonella typhi-infected rats was effectively ameliorated by intraperitoneal ketotifen, diphenhydramine and ranitidine but was worsen by exogenous histamine or diamine oxidase. In conclusion, enhancement of acid back-diffusion, mast cell histamine release and microvascular permeability is important in modulating gastric hemorrhage and ulcer in Salmonella typhi-infected rats.

Pharmacological effects of oxytocin on gastric emptying and intestinal transit of a non-nutritive liquid meal in female rats.

The effects of oxytocin (OT) on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in female rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na(2)(51)CrO(4). Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay. After administration of OT (0.2-0.8 mg/kg), gastric emptying and gastrointestinal transit were inhibited, whereas the plasma concentration of CCK was increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the OT- induced inhibition of gastric emptying and gastrointestinal transit. However, administration of atosiban alone had no effect on gastric emptying and gastrointestinal transit. The selective CCK(1) receptor antagonists, devazepide and lorglumide, effectively attenuated the OT-induced inhibition of gastric emptying and gastrointestinal transit. L-365, 260, a selective CCK(2) receptor antagonist, did not alter the OT-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that OT inhibits gastric emptying and gastrointestinal transit in female rats via a mechanism involving CCK stimulation and CCK(1) receptor activation.

Antihyperglycemic effect of andrographolide in streptozotocin-induced diabetic rats.

The antihyperglycemic action of andrographolide, an active principle in the leaves of Andrographis paniculata (Burm. f.) Nees, was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats). Oral treatment of andrographolide decreased the plasma glucose concentrations of STZ-diabetic rats in a dose-dependent manner. Similar treatment with andrographolide also decreased the plasma glucose in normal rats and the maximal effect was more marked than that in STZ-diabetic rats. Andrographolide at the effective dose (1.5 mg/kg) significantly attenuated the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. In the isolated soleus muscle of STZ-diabetic rats, andrographolide enhanced the uptake of radioactive glucose in a concentration-dependent manner. Moreover, the mRNA and protein levels of the subtype 4 form of the glucose transporter (GLUT4) in soleus muscle were increased after repeated intravenous administration of andrographolide in STZ-diabetic rats for 3 days. These results suggest that andrographolide can increase the glucose utilization to lower plasma glucose in diabetic rats lacking insulin.

Effects of evodiamine on gastrointestinal motility in male rats.

The effects of evodiamine on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in male rats. Evodiamine, isolated from the dry unripened fruit of Evodia rutaecarpa Bentham (a Chinese medicine named Wu-chu-yu), has been recommended for abdominal pain, acid regurgitation, nausea, diarrhea, and dysmenorrhea. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na(2)51CrO(4). Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay (RIA). After administration of evodiamine (0.67-6.00 mg/kg), both gastric emptying and gastrointestinal transit were inhibited, whereas the plasma concentration of CCK was increased in a dose-dependent manner. The selective CCK(1) receptor antagonists, devazepide and lorglumide, effectively attenuated the evodiamine-induced inhibition of gastric emptying and gastrointestinal transit. L-365,260 (3R-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl)-N'-(3-methylphenyl)-urea), a selective CCK(2) receptor antagonist, did not alter the evodiamine-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that evodiamine inhibits both gastric emptying and gastrointestinal transit in male rats via a mechanism involving CCK release and CCK(1) receptor activation.

Involvement of cholecystokinin receptor in the inhibition of gastric emptying by oxytocin in male rats.

The effects of oxytocin (OT) on gastric emptying and plasma levels of cholecystokinin (CCK) were studied in male rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na2(51)CrO4. Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Blood samples were collected for OT and CCK radioimmunoassay. After administration of OT (0.2-0.8 mg x kg(-1)), gastric emptying was inhibited, whereas plasma concentrations of OT and CCK were increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the OT-induced inhibition of gastric emptying. However, administration of atosiban alone had no effect on gastric emptying. Devazepide (3 mg x kg(-1)), a selective CCKA receptor antagonist, effectively attenuated the OT-induced inhibition of gastric emptying. L-365, 260, a selective CCKB receptor antagonist, did not alter the OT-induced inhibition of gastric emptying. These results suggest that OT inhibits gastric emptying in male rats via a mechanism involving CCK stimulation and CCKA receptor activation.

Role of acid back-diffusion, glutathione, oxyradical, and histamine in antral hemorrhagic ulcer in rats: the protective effect of lysozyme chloride and antioxidants.

The pathogenesis of gastric antral hemorrhage and ulceration is unclear. This paper first proposes that antral hemorrhagic ulcers produced in rats are associated with attenuation of defensive parameters (such as mucosal glutathione levels and histamine release, as well as aggravation of aggressive factors) including gastric acid back-diffusion and oxyradical generation. The protective effects of lysozyme chloride and antioxidants on this ulcer model were also evaluated. After being deprived of food for 24 hours followed by refeeding for 1 hour, rats were injected with 1.0 mol HCl/L intragastrically under potent analgesia of diethylether-anesthesia to induce antral ulcer. Control rats received a normal saline solution only. Rats were then given free access to water and food for 4 days. Before the experiment began, rats were again deprived of food for 24 hours. Following anesthetization, their stomachs were irrigated for 3 hours with either normal saline or a physiological acid solution containing 100 mmol HCl/L and 54 mmol NaCl/L. Aggravation of various aggressive and defensive parameters in antral mucosa was observed in refed rats that had received 1.0 mol HCl/L. A high relationship of mucosal glutathione level (r = -0.8754, P <.05) or lipid peroxides generation (r = 0.8198) to antral ulceration was obtained in those ulcerated rats. Intragastric lysozyme chloride (50-200 mg/kg) injected three times daily produced a dose-dependent attenuation of various gastric parameters in the acid-irrigated stomachs of antral ulcer rats. Intraperitoneal injections of various antioxidants, including exogenous glutathione, allopurinol, or dimethylsulfoxide also attenuated antral ulcer. In conclusion, the imbalance of aggressive factors, such as acid back-diffusion and oxyradicals-as well as defensive factors including glutathione and histamine-is important in modulating antral hemorrhagic ulcers that can be ameliorated by lysozyme chloride or antioxidants in rats.