Galectin-1 exhibits a protective effect against hepatotoxicity induced by dextran sulfate sodium in mice.

Galectin-1 is an important mediator that regulates the T-cell-mediated immune response. It has many other biological functions such as cell growth, immunomodulation, and wound healing. The aim of this study was to reveal the role of galectin-1 on liver morphology, cell proliferation, apoptosis, inflammatory and anti-inflammatory mediators, oxidative stress, and antioxidant system in colitis-mediated hepatotoxicity induced by dextran sulfate sodium (DSS). In the present study, adult mice were divided into four groups: The control group intraperitoneally injected with phosphate buffer saline (I), the group which was orally administered with DSS (II), the control group which was injected with galectin-1 (III), and the group which was given DSS and galectin-1 (IV). DSS administration caused degenerative changes and diffuse necrotic damage, an increase in caspase-3 and cyclooxygenase-2 expression, the levels of lipid peroxidation and tumor necrosis factor-alpha, lactate dehydrogenase, and myeloperoxidase activities, and a decrease in cell proliferation, interleukin-10 levels, and antioxidant system parameters in liver tissues. Treatment of DSS group with galectin-1 reversed these effects and prevented liver damage. This study showed that galectin-1 has proliferative, antiapoptotic, anti-inflammatory, and antioxidant effects against DSS-induced liver injury in mice. It is expected considering all results of this study that galectin-1 may be useful as a protective agent against liver toxicity.

4-Methylcatechol stimulates apoptosis and reduces insulin secretion by decreasing betacellulin and inhibin beta-A in INS-1 beta-cells.

Insulinoma INS-1 cell line is a pancreatic beta cell tumor which is characterized with high insulin content and secretion in response to increasing glucose levels. 4-Methylcatechol (4-MC) is a metabolite of quercetin, which is known as a potential drug for inhibition of tumorigenesis. The aim of this study was to determine the applying doses of 4-methylcatechol (4-MC) for triggening cell death and decreasing the cell function of rat insulinoma INS-1 beta cells. The rate of apoptosis and the amount of insulin in the cell and the secretions were determined by the ELISA method. Betacellulin (BTC) and inhibin beta-A amounts in both the cell and the glucose induced secretion were investigated by Western blotting. Furthermore, BTC, Inhibin beta-A, Ins1, Ins2, and GLUT2 gene expression levels were determined by the by the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) method. We noted a significant decrease in cell viability, while an increase in apoptotic cell death by 4-MC treatment. It caused a decrease in the secretion of BTC, expressions of both BTC and inhibin beta-A. We showed a decrease in the expressions of Ins1 and GLUT2, while there is no alteration in the level of insulin protein. Insulin secretion levels increased in INS-1 cells given 4-MC by basal glucose concentration while they did not response to high concentration of glucose, which indicates that 4-MC disrupts the functionality of INS-1 cells. These results revealed that 4-MC induces apoptosis and decreases insulin secretion by reducing BTC and inhibin beta-A in insulinoma INS-1 cells. Thus, 4-MC may be offered as a potential molecule for treatment of insulinoma.

Δ9-tetrahydrocannabinol treatment improved endothelium-dependent relaxation on streptozotocin/nicotinamide-induced diabetic rat aorta.

OBJECTIVE: In this study, we investigated the possible effect of Δ(9)-tetrahydrocannabinol (THC), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, on metabolic control and vascular complications of diabetes in streptozotocin/nicotinamide (STZ/NIC) induced type 2 diabetes mellitus. MATERIAL AND METHODS: Type 2 diabetes was induced with 65 mg/kg STZ, 15 minute later 85 mg/kg NIC was given intraperitoneally (i.p.) to rats. Three days after diabetes induction, THC (3 mg/kg/day, i.p.) was given for 7 days to diabetic rats. Body weight and plasma glucose levels of rats were measured in all groups before and at the end of 3 weeks after diabetes induction. Acetylcholine (Ach) and sodium nitroprusside (SNP) potency and maximum relaxant effects were calculated on aortic rings pre-contracted with noradrenaline (NA). RESULTS: At the end of 3 weeks, blood glucose levels of diabetic group significantly increased in comparison with the control group. Increased plasma glucose levels were significantly decreased by the treatment of THC. Ach induced relaxation was impaired whereas endothelium-independent relaxation to SNP was unaffected on isolated diabetic rat aorta. THC treatment enhanced Ach induced relaxation on diabetic rat aortas. DISCUSSION: These results suggested that THC improved endothelium-dependent relaxation in STZ/NIC induced diabetic rat aorta and that these effects were mediated at least in part, by control of hyperglycemia and enhanced endothelial nitric oxide bioavailability.

The relation among NGF, EGF and insulin is important for triggering pancreatic ß cell apoptosis.

BACKGROUND: Nerve growth factor (NGF) is a well-known mediator for maintaining the survival of neurons, while recent studies report that its absence induces apoptosis in cultured ß cells of humans and rats. However, its relationship with other growth factors that have important roles in the survival and function of ß cells such as epidermal growth factor (EGF) has not yet been elucidated. The aim of this study was to investigate the effects of NGF withdrawal on the synthesis and secretion of EGF, insulin with respect to ß cell apoptosis in hyperglycemic rats. METHOD: ß cells were isolated from euglycemic and streptozotocin-induced hyperglycemic rats and treated with NGF neutralizing antibody for withdrawal of NGF in culture medium. NGF, EGF and insulin levels in cell lysates and secretion samples were measured by enzyme-linked immunosorbent assay, and their gene expressions were determined by real-time reverse transcription polymerase chain reaction assay. Apoptosis was quantitatively determined by cytoplasmic histone-associated DNA fragments. RESULTS: Nerve growth factor neutralization triggered ß cell apoptosis. In addition decreased insulin, increased NGF and EGF were observed at gene expression and protein levels by NGF neutralization. Moreover, NGF withdrawal decreased secretion of these peptides from ß cells. Although the alterations seemed to be similar under euglycemic and hyperglycemic conditions, NGF withdrawal more strongly affected ß cells of hyperglycemic rats. CONCLUSIONS: These important findings indicate that NGF is an important regulator for the synthesis and secretion of EGF and insulin from the ß cells. Moreover, results suggested that NGF withdrawal causes apoptosis by decreasing EGF, NGF and insulin secretion from ß cells of hyperglycemic rats.

Ghrelin and insulin gene expression changes in streptozotocin-induced diabetic rats after rosiglitazone pretreatment.

The aim of the study was to evaluate the effect of rosiglitazone treatment on islet ghrelin and insulin gene expressions in streptozotocin (STZ)-induced diabetic rats. Animals were divided into four groups. 1. Intact controls. 2. Rosiglitazone-treated controls. 3. STZ-induced diabetes. 4. Rosiglitazone-treated diabetes. Rosiglitazone was given for 7 days at a dose of 20 mg/kg body weight. Ghrelin and insulin gene expressions were investigated by immunohistochemistry and in situ hybridization. There was no statistically significant difference in body weight between STZ-induced diabetic rats and rosiglitazone-treated diabetic rats during the experimental period. Furthermore, there were no significant differences in blood glucose levels and insulin immunoreactive cell numbers between STZ-induced diabetic rats and rosiglitazone-treated diabetic rats. There was a tendency towards a reduction of ghrelin gene expression in diabetic animals compared with intact controls. We found, in addition, that ghrelin immunoreactive and ghrelin mRNA expressing cells were frequent in the epithelial lining of the ducts suggesting ductal epithelium might be the source of the regenerating islet ghrelin cells, as is known for other islet cells. The results show that short-term rosiglitazone pretreatment had no significant effect on ghrelin and insulin gene expressions.

The effect of Z-FA.FMK on D-galactosamine/TNF-alpha-induced liver injury in mice.

Cathepsin B is a cysteine proteinase, considered to have an important role in apoptosis, which is activated by D-galactosamine and tumor necrosis factor-alpha (D-GalN/TNF-alpha). Benzyloxycarbonyl-L-phenylalanine fluoromethyl ketone (Z-FA.FMK) is a cathepsin B inhibitor used in research on apoptotic pathways. The aim of this study was to investigate the role of Z-FA.FMK on apoptotic cell death, cell proliferation and liver damage induced by a D-GalN/TNF-alpha combination in mice. In the study, 1 h after administration of 8 mg/kg Z-FA.FMK by intravenous injection, D-GalN (700 mg/kg) and TNF-alpha (15 microg/kg) were administered by a single intraperitoneal injection. In the group given D-GalN/TNF-alpha, the following results were found: Degenerative changes in the liver tissue, significant increase in the number of both TUNEL and activated caspase-3-positive hepatocytes, a decrease in the number of PCNA-positive hepatocytes, an increase in lipid peroxidation (LPO) levels and a decrease in glutathione (GSH) and DNA levels in the liver tissue. In contrast, in the group given D-GalN/TNF-alpha and Z-FA.FMK, a decrease in the damage of the liver tissue, a significant decrease in TUNEL and activated caspase-3-positive hepatocytes, a significant increase in the number of PCNA-positive hepatocytes, a decrease in the LPO levels, an increase in GSH and DNA levels in the liver tissue were found. As a result, microscopic and biochemical evaluations indicate that Z-FA.FMK plays a protective role against liver injury induced by D-GalN/TNF-alpha and it has an inverse effect on hepatocyte apoptosis and proliferation in BALB/c mice.

The effects of 5-aminoimidazole-4-carboxamide riboside on the pancreas in neonatal streptozotocin-diabetic rats.

In this study, we aimed to determine the alterations of beta-cell ultrastructure, insulin mRNA and protein products of the same gene on the pancreas of rats following long-term treatment of 5-aminoimidazole-4-carboxamide riboside (AICAR). A single dose of streptozotocin (STZ) 100 mg/kg was injected intraperitoneally (i.p.) to 2-day-old newborn (n2) rats. The rats were divided into three groups. The first group was the n2 STZ-diabetic rats. The second group consisted of n2 STZ-diabetic rats treated with AICAR 10 mg/kg/day for one month. The third group was non-diabetic control rats. Our findings demonstrate that AICAR treatment decreases the blood glucose level but increases the body weight in n2 STZ-diabetic rats. In the AICAR-treated group, numerous beta cells showed increased insulin gene expression. We also observed increased exocytosis in this group, in an ultrastructural manner. As a result, it is suggested that AICAR may induce insulin synthesis and betacell regeneration in n2 STZ-diabetic rats.

The effect of zinc supplementation on ghrelin-immunoreactive cells and lipid parameters in gastrointestinal tissue of streptozotocin-induced female diabetic rats.

Zinc is an essential nutrient with a wide range of functions and closely involved in a variety of enzymatic processes of importance in glucose, protein and lipid metabolism. Ghrelin is the endogenous ligand of the G protein coupled growth hormone secretagogue receptor. The regulatory mechanism that explain the biosynthesis and secretion of ghrelin in the gastrointestinal tract has not been clarified. This study was undertaken to examine the effect of zinc supplementation on the streptozotocin (STZ)-induced diabetic rats, which exhibits ghrelin production and secretion, and lipid metabolism on the gastrointestinal tract. The animals were divided into four groups. Group I: Non-diabetic untreated animals. Group II: Zinc-treated non-diabetic rats. Group III: STZ-induced diabetic untreated animals. Group IV: Zinc-treated diabetic animals. Zinc sulfate was given to some of the experimental animals by gavage at a dose of 100 mg/kg body weight every day for 60 days. In the zinc-treated diabetic group, the blood glucose levels decreased and body weight increased as compared to the diabetic untreated group. Zinc supplementation to STZ-diabetic rats revealed the protective effect of zinc on lipids parameters such as total lipid, cholesterol, HDL-cholesterol and atherogenic index. There is no statistically change in ghrelin-immunoreactive cells in gastrointestinal tissue. But, it has found that zinc supplementation caused a significant reduction in densities of ghrelin-producing cells of fundic mucosa of zinc-treated diabetic animals as compared to untreated, non-diabetic controls. Zinc supplementation may contribute to prevent some complications of diabetic rats, biochemically.

Protective role of Melissa officinalis L. extract on liver of hyperlipidemic rats: a morphological and biochemical study.

In this study, the effects of Melissa officinalis L. extract on hyperlipidemic rats were investigated, morphologically and biochemically. The animals were fed a lipogenic diet consisting of 2% cholesterol, 20% sunflower oil and 0.5% cholic acid added to normal chow and were given 3% ethanol for 42 days. The plant extract was given by gavage technique to rats to a dose of 2 g/kg every day for 28, 14 days after experimental animals done hyperlipidemia. The degenerative changes were observed in hyperlipidemic rats, light and electron microscopically. There was a significant increase in the levels of serum cholesterol, total lipid, alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), a significant decrease in the levels of liver tissue glutathione (GSH), a significant increase in the levels of tissue lipid peroxidation (LPO) in this group. On the other hand, the administration of Melissa officinalis L. extract reduced total cholesterol, total lipid, ALT, AST and ALP levels in serum, and LPO levels in liver tissue, moreover increased glutathione levels in the tissue. As a result, it was suggested that Melissa officinalis L. extract exerted an hypolipidemic effect and showed a protective effect on the liver of hyperlipidemic rats.

Protective effects of metformin treatment on the liver injury of streptozotocin-diabetic rats.

Metformin is a biguanide derivate used as an oral hypoglycaemic drug in diabetics. The aim of this study was to examine the histological and biochemical effects of metformin in streptozotocin (STZ)-treated rats. The animals were rendered diabetic by intraperitoneal injection of 65 mg/kg STZ. Fourteen days later, metformin was given at 25 mg/kg by gavage, daily for 28 days, to STZ-diabetic rats and a control group. In the STZ-diabetic group, some degenerative changes were observed by light microscopic examination. But the degenerative changes were decreased in the STZ-diabetic group given metformin. In the STZ-diabetic group, blood glucose levels, serum alanine and aspartate transaminase (ALT and AST) activities, total lipid levels, and sodium and potassium levels increased, while body weight, serum magnesium levels and liver glutathione (GSH) levels decreased. In the STZ-diabetic group given metformin, blood glucose levels, serum ALT and AST activities, total lipid, and sodium and potassium levels decreased, and liver GSH and serum magnesium levels increased. As a result of all the morphological and biochemical findings obtained, it was concluded that metformin has a protective effect against the hepatotoxicity produced by STZ diabetes.

The protective effect of vitamin C, vitamin E and selenium combination therapy on ethanol-induced duodenal mucosal injury.

In this study, the effect of a combination of vitamin C, vitamin E and selenium on ethanol-induced duodenal mucosal damage in rats was investigated morphologically and biochemically. The duodenal mucosal injury was produced by oral administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/ kg), vitamin E (250 mg/kg) and selenium (0.5 mg/kg) for 3 days and absolute ethanol 1 hour after last antioxidant administration and were sacrificed 1 hour after absolute ethanol. Extreme degeneration in intestinal mucosa of rats given ethanol was observed morphologically. In addition, an increase in neuronal nitric oxide synthase immunoreactive areas was observed in the rats of the group given ethanol. On the other hand, a normal morphological appearance and a decrease in neuronal nitric oxide synthase immunoreactive areas were detected in the rats given ethanol+vitamin C+vitamin E+ selenium. In the group to which ethanol was administered, an increase in serum cholesterol and a decrease in serum albumin levels were determined. On the other hand, in the group to which ethanol+vitamin C+vitamin E+selenium were administered, serum cholesterol value decreased, and the serum albumin level increased. As a result, we can say that the combination of vitamin C, vitamin E and selenium has a protective effect on ethanol-induced duodenal mucosal injury.

The morphological and biochemical effects of glibornuride on rat liver in experimental diabetes.

Glibornuride is a sulphonylurea derivative used as an oral hypoglycaemic drug in diabetics. The aim of this study was to examine the histological, ultrastructural and biochemical effects of glibornuride in streptozotocin (STZ)-treated rats. The animals were rendered diabetic by intraperitoneal injection of 65 mg/kg STZ. Fourteen days later, glibornuride was given at 5 mg/kg by gavage, daily for 28 days, to one STZ-diabetic and one control group. In the STZ-diabetic group, remarkable degenerative changes were observed. On the other hand, in the STZ-diabetic group given glibornuride, the degenerative changes decreased. In the STZ-diabetic group, blood glucose levels, serum aspartate transaminase activity, and total lipid levels increased, whereas the blood glutathione levels decreased. In contrast, in the STZ-diabetic group given glibornuride blood glucose levels, serum aspartate transaminase activity and total lipid levels decreased and blood glutathione levels increased. Significant changes in total protein levels in the serum were not observed in any group. As a conclusion, we can say that glibornuride has a protective effect against the hepatotoxicity produced by STZ-diabetes.

Effects of parsley (Petroselinum crispum) on the liver of diabetic rats: a morphological and biochemical study.

Parsley is used by diabetics in Turkey to reduce blood glucose. The present study aims to investigate both the morphological and biochemical effects of parsley on liver tissue. Rat hepatocytes were examined by light and electron microscopy. Degenerative changes were observed in the hepatocytes of diabetic rats. These degenerative changes were significantly reduced or absent in the hepatocytes of diabetic rats treated with parsley. Blood glucose levels, alanine transaminase and alkaline phosphatase were observed to be raised in diabetic rats. Diabetic rats treated with parsley demonstrated significantly lower levels of blood glucose, alanine transaminase and alkaline phosphatase. The present study suggests that parsley demonstrates a significant hepatoprotective effect in diabetic rats.

The effects of chard (Beta vulgaris L. var. cicla) extract on the kidney tissue, serum urea and creatinine levels of diabetic rats.

The aim of this work was to investigate the effects of chard (Beta vulgaris L. var. cicla) extract on serum urea and creatinine concentrations and on kidney tissue in normal and streptozotocin-diabetic rats. The extract was administered to rats at a dose of 2 g/kg every day for 28 days, 14 days after animals were made diabetic. On day 42, kidney tissue and blood samples were examined. Significant degenerative changes in kidney tissue of diabetic rats were observed, but in the group given chard extract, the morphology of kidney tissue was found to be nearly the same as the controls. Serum urea and creatinine levels significantly increased in the diabetic groups, but the chard extracts significantly reduced serum urea and creatinine levels. It is concluded that the extract of this plant may reduce serum urea and creatinine levels and confer a protective effect on the kidney of diabetic rats.

Effects of the ionophores valinomycin, ionomycin and gramicidin A on the element compartmentation in cultured rat hepatocytes.

The element compartmentation in cultured rat hepatocytes was studied by electron probe X-ray microanalysis of freeze-dried cryosections after exposure of the cells to the ionophores valinomycin, ionomycin or gramicidin A. The most striking effect of these ionophores is the decrease of the intracellular potassium/sodium ratio from values of approximately 10 under control conditions to values below 1 after application of the ionophores. Changes of sodium, potassium and chloride are similar in cytoplasm and nucleus. However, elemental changes are delayed or impeded in mitochondria with respect to the surrounding cytoplasm. The water portion of cytoplasm and mitochondria slightly increases. Besides that, each ionophore has specific effects on the intracellular ion distribution. As compared to gramicidin A and ionomycin, valinomycin does not change the intracellular chloride content. Ionomycin induces calcium accumulation in mitochondria. The cytotoxic effects of the studied ionophores on the intracellular element distribution are more complex than supposed from their ion selective properties in membranes.

Effects of acid inhibition on somatostatin-producing cells in the rat gastric fundus.

Somatostatin plays a role in the regulation of gastric acid secretion. Omeprazole, a potent inhibitor of gastric acid secretion, has been reported to cause either a significant decrease or increase in the formation of gastric somatostatin-producing cells. Therefore, we determined in the present study distribution patterns of somatostatin mRNA and protein in fundus mucosa of rats after long-term inhibition of gastric acid secretion. Female Sprague-Dawley rats were given 0, 20 and 100 mg/kg/day omeprazole, respectively, as gastric instillations during 2 months. Serum gastrin levels were significantly higher in the third group than in the other groups. The omeprazole-treated groups also showed an increase in the number of somatostatin-containing cells in fundus mucosa. Moreover, the intensity of somatostatin-positivity was higher in the treated groups than in the control group. We also observed an increase in the number of cells containing somatostatin mRNA in fundus mucosa of omeprazole-treated rats. These results suggest that long-term inhibition of acid secretion does not inhibit but stimulate somatostatin production in mucosa of rat gastric fundus.

Protective effects of DL-alpha-tocopherol acetate and sodium selenate on the liver of rats exposed to gamma radiation.

The aim of this study is to investigate whether vitamin E (as DL-alpha-tocopherol acetate) and selenium (as sodium selenate) exert a protective effect against radiation damage. The liver tissue of rats irradiated with a single dose of 1,000 cGy 60Co-gamma-irradiation was examined for morphological changes after the intraperitoneal (ip) administration DL-alpha-tocopherol acetate and sodium selenate as compared to controls. Also, the amounts of blood glutathione and serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and total protein were determined by spectrophotometric methods. Degenerative changes were observed under light and electron microscopy in the liver tissue of the control (radiation only) group. In the group receiving radiation and ip doses of DL-alpha-tocopherol acetate and sodium selenate, the damage to the liver tissue was minimal or absent. In the radiation-only group, a reduction of the blood glutathione level and increases in serum values of AST, ALT, ALP, and LDH activity were observed, whereas in the irradiation-treated group, the reverse was found to occur. Based on these morphological and biochemical observations, it was concluded that the ip administration of DL-alpha-tocopherol acetate and sodium selenate exerts a protective effect against liver radiation damage.

Effects of chard (Beta vulgaris L. var. Cicla) extract on pancreatic B cells in streptozotocin-diabetic rats: a morphological and biochemical study.

Chard (Beta vulgaris L. var. cicla) is used as a hypoglycemic agent by diabetic patients in Turkey. The present study was carried out in order to detect whether this plant, used in folk remedies for decreasing blood glucose levels, affects pancreatic B cells and blood glucose. In the diabetic group, a decrease in the number of B cells of Langerhans islets and in the secretory materials, a swollen granular endoplasmic reticulum cisternae and widened intercellular areas in some of B cells were observed. But, in a diabetic group given chard extract, an increase in the number of B cells of Langerhans islets and in the secretory granules were noted, together with many hypertrophic Golgi apparatus and granules of low densities. The extract while having no effect on blood glucose and body weight in the normal group, reduced the blood glucose value in streptozotocin-induced hyperglycemic animals. But, in a diabetic group given chard, the body weight significantly increased in comparison to the diabetic group; maximum reduction in blood glucose levels was observed on the 42nd day. According to the morphological and biochemical results obtained, it is concluded that the extract of this plant when administered by gavage may reduce blood glucose levels by regeneration of the B cells.

Detection of c-erbB-2 mRNAs using dig-labelled oligonucleotide probe with in situ hybridisation in human breast carcinoma: comparison with immunohistochemical results.

Amplification and overexpression of the c-erbB-2 oncogene are of prognostic significance in human breast cancer. Overexpression of c-erbB-2 is the result of gene amplification. However, increased transcript levels of c-erbB-2 are also detected in the absence of gene amplification. In this study for the detection of the overexpression mRNA in situ hybridisation (ISH) and immunohistochemistry (IHC) were used. Our aim was to develop the suitable mRNA ISH protocol for formalin-fixed paraffin-embedded material and to compare the localisation of transcripts and protein products in 20 primary breast carcinomas. Sections were immunostained with monoclonal c-erbB-2 antibody. In ISH method digoxigenin-labelled oligoprobe was used for the detection of c-erbB-2 mRNAs. We determined optimal condition for the ISH procedure (e.g., probe concentration, digestion, post washing). c-erbB-2 protein overproduction was detected in 11/20 cases with IHC. The mRNA signals were observed in malignant cell cytoplasm in 6/20 cases by ISH. ISH positive signals were found in only one case without detected overexpression of the protein. There were cell to cell variations in the hybridisation signals even within individual tumours. The ISH and IHC positive signals for c-erbB-2 was observed mostly in infiltrating ductal carcinomas that belong to aggressive lesions.

Alterations in gastrin cells induced by short-term omeprazole treatment in the rat antrum: an immunocytochemical and in situ hybridization study.

Gastrin is a hormonal regulator of gastric acid secretion and a trophic stimulant of acid-producing gastric mucosa. The blockage of acid secretion has been reported to cause hypergastrinaemia and gastrin cell hyperplasia. These findings suggest that achlorhydria may stimulate gastrin gene expression in gastrin cells. In this study, we aimed to determine the alterations of gastrin mRNA by non-radioactive in situ hybridization, and also to compare the localization of transcripts and protein products of the same gene by immunocytochemistry in an acid inhibition environment provided by omeprazole. Female Sprague-Dawley rats, weighing 200-250 g, were divided into three groups. The first group was the control group (eight rats). The second group (eight rats) was given 20 mg kg-1 day-1 omeprazole as intragastric instillations for 4 days. The third group (eight rats) was given 100 mg kg-1 day-1 omeprazole as in the second group. Serum gastrin levels in the two groups treated with omeprazole showed a statistically significant increase (P < 0.001) compared with the control group. The omeprazole-treated groups also showed an increase in the number of immunoreactive gastrin cells in the pyloric mucosa and an enhancement in the intensity of immunoreaction. Cells containing gastrin mRNA signals were observed in the upper regions of the pyloric glands in the pyloric sections of the control group and in both experimental groups.