Gastroprotective effect of vanadium in rats - the roles of gastric acid and nitric oxide

Vanadium (various forms) has been proven to be beneficial in the treatment of certain diseases, especially diabetes. Reports have it that vanadium may protect the stomach from gastric ulcerogens such as ethanol and acid. This study was designed to investigate the probable mechanism Vanadium exerts its’ gastroprotective activities.Methods: Sodium metavanadate (0, 5, 10 and 20 mg/kg. p.o) was administered to 20 male Wistar rats weighing (150±20g) for two weeks. Gastric ulcer was induced using ethanol after which animals were sacrificed 2 hours later. In study two, 30 male Wistar rats (114±10g) were administered sodium metavanadate at (0, 50 and 200 ppm) in drinking water for 10weeks after which ulcer was induced using pylorus ligation method. Basal and histamine (10mg/kg i.m) stimulated gastric secretions were determined through continuous perfusion technique afterwards in un-ulcerated animals. Ulcer score, mucin content, gastric nitrite level, anti-oxidant and H+K+ATPase activities were investigated in gastric homogenate samples.Results: Sodium metavanadate significantly reduced ulcer index and MDA levels while enhancing NO concentrations, catalase and SOD activities in both method of gastric ulceration. Mean basal gastric output was not significantly different in control compared with 50 and 200 ppm V group. Stimulation with histamine caused significant increases in gastric output by 187.72%, 57.40% and 78.69% in control, 50 and 200 ppm V respectively and was significantly reduced in the vanadium treated groups. A significant decrease in H+K+ ATPase (proton) pump activities of the vanadium exposed groups compared with control in the pylorus ligation ulcer model was observed.Conclusion: Vanadium may be suggested to have protective activities against gastric ulceration by acting as a proton pump inhibitor, enhancing anti-oxidant enzyme activities as well as mucosal blood flow via increased NO mechanism.Keywords: Sodium Metavanadate, Gastric Ulcer, Gastric Acidity, Oxidative Stress, Nitric Oxid

Evaluation of a cement dust generation and exposure chamber for rodents: blood heavy metal status, haematological variables and gastrointestinal motility in rats

Exposure to cement dust has been documented to cause various occupational and long-term health complications both in human and animal. However, investigations on the extent of toxicity associated with cement dust exposure have been limited by lack of suitable model for controlled laboratory exposures. In this study, a glass house animal exposure chamber was fabricated using a plexi-glass and a blowing fan of adjustable revolution. Model simulations were validated using experimental data showing the effects of cement dust exposure on haematological indices, trace element status and gastrointestinal motility in rats. Thirty male Wistar rats were randomly divided into three groups. The unexposed group (n = 10) served as control while the other groups were exposed for five hours daily to cement dust (200g) at a revolution of 2400-3000rpm. Blood collected was analysed for some haematological variables as well as plasma concentrations of cadmium, lead, silicon, aluminium, manganese, calcium, iron and magnesium. Organ weights were measured and histopathological features of the kidney, lungs stomach and liver were assessed to determine the degree of tissue damage. Intestinal motility was assessed in vivo using the Charcoal meal method while colonic motility was studied by measuring the distance travelled by beads inserted 2cm into the distal colon through the anal opening. Data were expressed as Mean ± SEM, analysed using one-way ANOVA and p<0.05 was significant. Blood analysis from exposed rats on days 14 and 28 showed significant increase in concentrations of Calcium, Silicon, Manganese, Iron, Lead, Cadmium, Aluminium and magnesium compared with unexposed animals. Significant reductions were observed in haematocrit values, red and white blood cell counts after cement dust exposure. Also, significant increases were observed in the neutrophil-lymphocyte ratio and erythrocyte sedimentation rate in exposed rats compared with control. There was a significant decrease in organ weights - stomach, lungs, kidney when compared with control. Rats exposed to cement dust had significantly decreased small intestinal motility but increased colonic transit time. Histopathological examination from exposed rats revealed peribronchiolar infiltration by lymphocytes in the lungs while gastric gland was severely infiltrated by inflammatory cells. The results from this study are comparable to data obtained from earlier reported on haematological and heavy metals in humans occupationally exposed to cement.Keywords: Cement dust, fabricated chamber, haematological indices and gastric motilityAfr. J. Biomed. Res. Vol. 22 (January, 2019); 79- 8

Role of nitric oxide and endogenous antioxidants in thyroxine facilitated healing of ischemia-reperfusion induced gastric ulcers

Background: Studies have revealed the role of thyroxine during healing of gastric ulcers with information lacking on the mechanism involved hence the focus of this study.Materials and Methods: Adult male Wistar rats (150 – 200g) were randomly divided into 4 groups (n=5 per group): Normal control (NC), Sham ulcerated (SU), Thyroidectomised ulcerated untreated (ThU) and Thyroidectomised ulcerated + Levo-thyroxine (100μg/kg/day) (ThU + T4). Animals were stabilised for 35 days following thyroidectomy and treated accordingly to experimental groupings. Weekly body weight changes were recorded, gastric ulcer was induced by ischemia-reperfusion and gastric acid secretion evaluated. They were sacrificed 1 hour, 3 and 7 days post ulcer induction, blood samples collected for haematological indices through cardiac puncture and their stomachs prepared for gross and microscopic examinations to assess gastric healing. Gastric tissue protein, malondialdehyde (MDA), Superoxide Dismutase (SOD), Catalase (CAT), and Nitric oxide (NO) were assessed as biomarkers of healing. Data were analysed using one way ANOVA and Student’s t test with p< 0.05 considered statistically significant.Results: Thyroxine treated rats showed significant weight loss compared with NC and ThU groups. Percentage healing rate was significantly increased in thyroxine treated group compared with ThU animals by 1 hour (42.45% and -42.81%), days 3 (35.14% and -59.36%), and 7 (64.29% and -115.7%). Hematological indices significantly increased in thyroxine treated group compared with other groups. Thyroxine treatment significantly reduced Neutrophil/Lymphocyte; Platelet/NO as well as lipid peroxidation index in this study. Superoxide dismutase, CAT and NO increased significantly in thyroxine treated rats compared with other groups.Conclusion: Thyroxine treatment facilitates the healing of ischeamic-reperfused  gastric ulcers possibly by increasing NO activity which in turn causes increased vasodilatation and enhanced endogenous antioxidants at the ulcer sites.Keywords: Nitric Oxide, Antioxidants, Thyroidectomy, Levo-thyroxine, Ulcer healing

Pro-ulcerogenic activity of sodium arsenite in the gastric mucosa of male wistar rats

Background: The gastrointestinal tract is constantly exposed to various protective and aggressive factors from food and the environment. Recent studies have shown that environmental factors, including heavy metal exposure and diet may alter gastrointestinal mucosal integrity. Arsenic (extensively available in the form of oxides or sulfides or as a salt of iron, sodium, calcium, copper, etc) is a major contaminant of soil, air as well as various water sources used for human and industrial activities, making it a huge public health burden. The present study was designed to characterize gastrointestinal alterations induced by sodium arsenite (SA) exposure.Methods: Sixty-four male Wistar rats were divided into four groups (n = 16) in two separate studies. Groups I and 2 received distilled water and indomethacin (40mg/kg, p.o) respectively while groups 3 and 4 animals received 5mg/kg and 10mg/kg SA respectively for two weeks prior to administration of indomethacin. In the first study, gastric acid secretion (GAS) was studied using the continuous perfusion technique. In the second study, animals were sacrificed after indomethacin administration. Ulcer was assessed based on macroscopic appearance of the stomach using an ulcer score scale. Each excised stomach was thoroughly cleaned and small sections were taken for histological analysis. Data were analysed using one-way ANOVA and differences considered significant at p<0.05.Results: Basal GAS was 0.08 ± 0.004 mEq/L in control rats. Indomethacin increased GAS significantly (0.14 mEq/L). The effect of indomethacin was augmented in rats with prior exposure to SA in a dose-dependent manner (0.17±0.01 and 0.26±0.02 mEq/L respectively). In the second study, SA significantly increased mean ulcer score, parietal and mucous cell counts when compared with the unexposed groups. Moderate epithelial erosion with infiltration of inflammatory cells as well as decreased intraglandular mucin and mucous secreting cells were observed in the stomach tissues of sodium arsenite treated rats.Conclusion: It is suggested that sodium arsenite potentiates gastric ulceration during indomethacin induced ulceration by increasing basal gastric acid secretion, increased parietal cell counts with extensive damage to the mucous secreting cells thereby distrupting the cyto-protecting ability of the stomach.Keywords: Sodium arsenite, gastric ulcer, gastric acid secretion, parietal cell coun

Molecular epidemology: a better approach for the early detection of pathophysiologic response to environmental toxicants and disease

Our environment is becoming increasingly contaminated by a profusion of substances in the form of industrial and Municipal Waste, air and water pollutants; by heavy metals (such as lead) herbicides, pesticides, cosmetics and so on. The number of chemicals that affect man increases at alarming rates. These agents may be dangerous because they produce biochemical, genetic, structural or physiological lesions in a significant segment of the population. The importance of elucidating the nature and the mechanisms of physiological and toxicological reactions has been emphasized in the investigations of occupational and environmental diseases, such investigations have revealed that the clinical manifestations of intoxication may have their origin in injurious effects of subcellular or biochemical types. Slight to moderate derangements in metabolism may impair the functional activity of organs and lead to subclinical or overt clinical effects. These may elude detection or recognition of their health implications unless biomarkers, the functional components of molecular epidemiology are employed. Molecular epidemiology is an approach which aims to examine aetiology of disease in a more precise way by focusing on biomarkers of disease risk rather than relying on the actual occurrence of disease. Such studies can be carried out in a short time and with relatively small numbers of subjects compared with conventional epidemiology, which though currently more popular merely reveals association, and causal links often remain obscure. Detection of early biochemical lesions that are related to subsequent changes in structure and physiology would be useful as early indicators of environmental hazards that produce disease in humans, that is by employing molecular epidemiology. This will be greatly enhanced by newer tools, such as toxicogenomics and metabonomics

Standardized experimental model for cement dust exposure; tissue heavy metal bioaccumulation and pulmonary pathological changes in rats

A controlled experimental model of exposure to aerosols particularly for cement dust was recently invented in a study from the laboratory that found high serum levels of heavy metals, decrease gastrointestinal motility, and altered hematological variables in cement dust exposed rats. However, reproducibility was not considered. This work aims at standardizing the model and investigating preliminary toxicological indicators. Thirty male rats used in this study were divided into 3 groups (n = 10). Group 1; control, while groups 2 and 3 were exposed to cement dust for 14 days and 28 days respectively. We assessed clinical signs of toxicity, tissue heavy metal concentration, histopathological, and body weight (BW) changes. We observed poor movement coordination, abnormal posture, cephalic fur loss. Evidence of ischemia and fibrotic pneumoconiosis were grossly observed in the lungs of the exposed groups. There was a significant increase in tissue level of heavy metals with pulmonary and gastric heavy metal content showing a trendy relationship during the period of the exposure as the value of Lead, Chromium, Cadmium, Iron, Calcium, and Nickel increased by nearly similar percentages in both tissues. Organs weights increased; the 14-day exposed (198 ± 31; 168 ± 22) and 28-day exposed (198 ± 22; 187 ± 26) groups had significantly reduced body weight at the first and second weeks of exposure compared to the control group (265 ± 26; 357 ± 40) respectively. Exposure to cement dust induced low bone density in the exposed rats (p < 0.05). Histopathological alterations include necrosis, inflammatory cellular infiltration, and alveolar hyperplasia suggestive of the proliferative response of pulmonary tissue to the dust. The operation of the standardized apparatus mimics a typical occupational exposure and the findings show that cement dust induces systemic toxicity via respiratory perturbation and body/organ weight discordance mediated by heavy metal bioaccumulation

Catecholamines Inhibit Gastric Epithelial [RGM-1] Cell Proliferation via Beta Adrenoceptors

Catecholamines have been implicated in the modulation of normal cell growth, exerting inhibitory or excitatory control depending on the cell type. However, there is a dearth of information on the role of adrenergic mediators in gastric cell proliferation. In the present study, the effects of adrenaline (ADR) and noradrenaline (NOR) on mucosal cell growth and the cell cycle were evaluated in vitro using a normal rat gastric mucosal cell line RGM-1. Cell proliferation was assessed using [3H]-thymidine incorporation and cell cycle patterns were determined by DNA labeling with propidium iodide and flow cytometric quantification. The expressions of adrenoceptors in RGM-1 were determined by Western blot. ADR (0.01 – 10μM) and NOR (0.01 – 10μM) inhibited the growth of RGM-1 cells in a concentration-dependent manner. Pre-treatment of cells with ADR and NOR also inhibited the proliferation stimulated by epidermal growth factor (EGF). Neither phentolamine (non-selective α-adrenergic blocker), methoxamine (α1-selective agonist) nor clonidine (α2-selective agonist) significantly affected the inhibition of cell proliferation produced by ADR and NOR. Propranolol (non-selective β-adrenergic blocker) and butoxamine (selective β2-adrenergic blocker) significantly (but not totally) reversed the inhibitory action of ADR on cell proliferation. Furthermore, procaterol (selective beta-2 agonist) but not dobutamine (selective beta-1 agonist) had effects similar to those produced by ADR and NOR. Exposure of RGM-1 cells to both ADR and NOR caused significant inhibition of the G1 – S cycle progression as evidenced by the higher percentage of the G0/G1 phase and a decreased S- phase. This effect was blocked by pre-treatment with propranolol but not phentolamine These results indicate that catecholamines inhibit the proliferation of RGM-1 cells probably partly through beta-2 receptors

Molecular epidemology: a better approach for the early detection of pathophysiologic response to environmental toxicants and disease

Our environment is becoming increasingly contaminated by a profusion of substances in the form of industrial and Municipal Waste, air and water pollutants; by heavy metals (such as lead) herbicides, pesticides, cosmetics and so on. The number of chemicals that affect man increases at alarming rates. These agents may be dangerous because they produce biochemical, genetic, structural or physiological lesions in a significant segment of the population. The importance of elucidating the nature and the mechanisms of physiological and toxicological reactions has been emphasized in the investigations of occupational and environmental diseases, such investigations have revealed that the clinical manifestations of intoxication may have their origin in injurious effects of subcellular or biochemical types. Slight to moderate derangements in metabolism may impair the functional activity of organs and lead to subclinical or overt clinical effects. These may elude detection or recognition of their health implications unless biomarkers, the functional components of molecular epidemiology are employed. Molecular epidemiology is an approach which aims to examine aetiology of disease in a more precise way by focusing on biomarkers of disease risk rather than relying on the actual occurrence of disease. Such studies can be carried out in a short time and with relatively small numbers of subjects compared with conventional epidemiology, which though currently more popular merely reveals association, and causal links often remain obscure. Detection of early biochemical lesions that are related to subsequent changes in structure and physiology would be useful as early indicators of environmental hazards that produce disease in humans, that is by employing molecular epidemiology. This will be greatly enhanced by newer tools, such as toxicogenomics and metabonomics

Augmentation of gastric acid secretion by chloroquine and amodiaquine in the rat stomach

Gastrointestinal mucosal integrity has been shown to be altered by chloroquine and amodiaquine, although the exact mechanism is not clear. Since Gastric Acid Secretion (GAS) plays significant role in the etiology of ulcer, the present study was aimed at investigating the effect of chloroquine and amodiaquine on GAS, Parietal Cell Mass (PCM) and Gastric Mucous Cell Population (GMP) in rats. Male albino wistar rats were randomly assigned into three groups viz: control, chloroquine (CQ, 3 mg/kg), amodiaquine (AQ, 10 mg/kg). Basal GAS as well as secretion in response to histamine and carbachol was measured by continuous perfusion of the stomach with normal saline (1ml/minute) under urethane anaesthesia (0.6 mg/100 g). After obtaining a steady basal output response to normal saline in all animals, the antimalaria drugs were administered intramuscularly and the peak responses to each drug obtained. Further assessment of the roles of histaminergic and muscarinic receptors were done using ranitidine (H2 antagonist) and atropine (M antagonist) in the treated animals. PCM and GMP were determined in the stomach samples by histometry. The basal acid output was 0.70 ± 0.01 mmol/10 mins. Chloroquine and amodiaquine produced increase in acid output to a peak of 1.35 ±0.03 mmol/10 mins (92.9%, p<0.001) and 1.40 ± 0.03 mmol/10 mins (100%, p<0.001) respectively. Histamine and carbachol elicited 107% and 100% increase acid secretion when compared with the basal output respectively. CQ and AQ potentiated histamine-induced secretory rate which peaked at 1.60 ± 0.02 mmol/10 mins and 1.70 ± 0.03 mmol/10 mins respectively. Similarly, the carbachol-induced acid secretory response was potentiated by CQ and AQ to a peak of 1.45 ± 0.02 mmol/10 mins and 1.50 ± 0.03 mmol/10 mins (p<0.05). Ranitidine and atropine attenuated histamine and carbachol induced acid secretion, but did not abolish it. CQ and AQ increased significantly the parietal cell numbers in the gastric mucosa (21±0.7 and 24±0.7 versus 15.2±0.8 control; p<0.05). On the other hand, mucus cell population was significant decreased by CQ and AQ (15±0.3 and 13±0.85 versus 17.4±0.5 control; p<0.05) respectively. Chloroquine and amodiaquine increased gastric acid secretion in rats. They stimulated histamine (H2) and muscarinic (M3) receptors, and enhanced parietal cell mass

Effect of Sulfadoxine-Pyrimethamine and Artesunate on Gastric Acid Secretion and Parietal Cell Mass in Rats

In this study, the effects of two antimalarial drugs, sulfadoxine-pyrimethamine and artesunate, on Gastric Acid secretion (GAS), Parietal Cell Mass (PCM) and Gastric Mucous Cell Population (GMP) were investigated in rats randomly assigned into three groups viz: control, Sulfadoxine-pyrimethamine (SP, 1.25/25 mg/kg), artesunate (AS, 2 mg/kg). Basal GAS as well as secretion in response to histamine and carbachol was measured by continuous perfusion of the stomach with normal saline (1ml/minute) under urethane anaesthesia (0.6 mg/100 g). After obtaining a steady basal output response to normal saline in all animals, the antimalaria drugs were administered intramuscularly and the peak responses to each drug obtained. Further assessment of the roles of histaminergic and muscarinic receptors were done using ranitidine (H2 antagonist) and atropine (M3 antagonist) in the treated animals. PCM and GMP were determined in the stomach samples by histometry. The basal acid output was 0.70 ± 0.01 mmol/10 mins. Normal saline and SP produced no statistically different peak output compared with the basal (p>0.05). AS produced a significant reduction with a value of 0.45 ± 0.03 mmol/10 mins (p<0.05). Histamine and carbachol elicited 107% and 100% change of acid secretion when compared with the basal output with the value of 1.45 ± 0.04 mmol/10 mins and 1.40 ± 0.03 mmol/10 mins respectively (p<0.001). SP and AS attenuated histamine-induced acid secretory rate with the peak value of 0.95 ± 0.01 mmol/10 mins and 0.80 ± 0.02 mmol/10 mins respectively. Similarly, the carbachol-induced acid secretory response was attenuated by SP and AS to a peak of 0.90 ± 0.02 mmol/10 mins and 0.90 ± 0.03 mmol/10 mins (p<0.05). SP and AS decreased significantly the parietal cell numbers in the gastric mucosa (13.8± 0.3 cells/μm versus 15.2±0.8 cells/μm control; p<0.05) and (13.4±0.5 cells/μm versus 15.2±0.8 cells/μm control; p<0.05). On the other hand, mucus cell population was significant increased by SP and AS (19±0.7 cells/μm versus 17.4±0.5 cells/μm control; p<0.05) and (22.2±0.8 cells/μm versus 17.4±0.5 cells/μm control; p<0.05) respectively. Sulfadoxine-pyrimethamine and artesunate inhibit gastric acid secretion. They inhibited histamine (H2) and muscarinic (M3) receptors, and reduced parietal cell mass