Naringenin modulates Cobalt activities on gut motility through mechanosensors and serotonin signalling.

IntroductionCobalt chloride-(CoCl2) exerts beneficial and toxic activities depending on dose however Naringenin-(Nar) a flavonoid, chelates heavy metals. Absorption of ingested heavy metals, or chelates are dependent on gut motility (gastric emptying and intestinal transit time) and mechanosensor regulation. Literature is vague on CoCl2 activities on gut motility and mechanosensor nor probable chelating actions with naringenin which was investigated in this study.MethodOne hundred male Wistar rats were grouped viz; A to D (25, 62, 150 and 300 mg/kg CoCl2), E to H doses of CoCl2+Nar (50 mg/kg), I-Narigenin and J-Control. Gastric emptying and intestinal transit time were evaluated by day eight, intestinal tissue assayed for biochemical, histological and immunohistochemistry reactivity.ResultCoCl2 significantly increased Gastric emptying (150 and 300 mg/kg) and Intestinal transit time unlike Naringenin. CoCl2 (150 mg/kg) significantly increased Catalase and Nitric oxide but ameliorated by Naringenin. ATPase activities significantly increased in 150 mg/kg-CoCl2 but ameliorated by Naringenin. Carbonyl levels increased in all CoCl2+Nar groups. High Enterochromaffin-cell count in 25 and 62 mg/kg-CoCl2 were ameliorated by Naringenin. Serotonin immunoreactivity increased in CoCl2 (25, 62, 300 mg/kg) but reduced in CoCl2+Nar groups.ConclusionCobalt chloride enhanced gastric motility via increased mechanosensor activities and serotonin expression at low doses. Naringenin ameliorated toxicity of high cobalt chloride via metal-flavonoid chelates.

Low-dose Potassium bromate enhances ischemia-reperfusion-induced gastric ulcer healing in Thyroidectomised Rats.

Gastric ulcer healing is impaired in both hypothyroid and hyperthyroid conditions.  Thyroid hormones regulate growth, energy metabolism and mitochondrial oxidative metabolism. Xenobiotics have been documented to negatively impact the thyroid gland at high doses but the redox and cellular interactions at low doses during wound healing process remains unclear. Potassium bromate has been documented to be toxic at high doses but there is dearth of information on its activities at a low dose in varied thyroid states which was evaluated in this study. 60 male Wistar rats (g, n=10) were randomised into 2 conditions: Normal, ulcerated untreated, ulcerated treated with 12.5mg/kg p.o KBrO3 and thyroidectomised groups: thyroidectomised ulcerated, thyroidectomised ulcer treated with KBrO3 and thyroidectomised treated with thyroxine (100µg/kg) Total thyroidectomy was used to model hypothyroidism, and ischaemia-reperfusion-induced gastric ulcers were monitored for healing. Daily body weights, Levels of thyroxine, Gastric mucin content, redox and sodium pump activity were examined alongside other markers of hepatic and haematological toxicity by days 3 and 7 post ulceration. Data were analysed using descriptive statistics and ANOVA α 0.05. The bromate-exposed hypothyroid rats showed increased gastric ulcer healing potential with reduced gastric epithelial oedema and inflammation; hepatic steatosis, and periportal inflammation. Haematological variables and markers of hepatic functions were normal. There were reduced levels of gastric and hepatic malondialdehyde levels. Thyroxine and potassium bromate treatment resolved the redox and cellular toxicity possibly via increasing catalase and sulfhydryl levels and increased Na+ K+ pump activity. We conclude that potassium bromate enhanced gastric ulcer healing in hypothyroid state, similar to thyroxine treatment.

Short-term acute constipation and not short-term acute diarrhea altered cardiovascular variables in male Wistar rats.

Gastrointestinal dysmotility is a substantial public health challenge globally. Based on previous findings in developed countries, it has been observed that there is an association between diarrhea, constipation, and some cardiovascular variables. This study investigated the effects of experimentally-induced short-term acute constipation and short-term acute diarrhea on certain cardiovascular variables in rats. Thirty (30) male Wistar rats (150 -180 g) were divided into three groups; Control, Diarrhoea, and Constipation. The experiment was carried out in 2 phases, the period after induction and the recovery period, and 5 animals per group were used for each phase. The control group received an equivalent amount of distilled water while Diarrhoea and the Constipation group were induced by oral administration of 2ml Castor oil and administration of Loperamide (3mg/kg, b.d, orally x 3 days), respectively. Cardiovascular variables were assessed using the Edan Scientific® Electrocardiography and  Heart Rate Variability machine. Recovery was allowed for 4 days after the onset of the procedure and cardiovascular parameters were reassessed. Post-induction Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP) and Heart Rate (HR) significantly increased in constipated rats (153.2 ± 2.9 mmHg; 109.0 ± 3.7 mmHg;     123.7 ± 3.2 mmHg; 123.4±5.6 bpm) when compared with the control values (95.5±4.8 mmHg; 61.2 ± 3.5 mmHg; 72.6 ± 3.6 mmHg; 72.3 ± 5.2 bpm), respectively. The recovery SBP, DBP, MAP, and Heart Rate in the constipated group remained significantly higher compared to the control. Diarrhea had no significant effect on the parameters determined in both post-induction and recovery phases. The electrical activities did not change in both experimental groups compared to the control. This study revealed increased SBP, DBP, MAP, and HR in short-term acute constipated rats but not so with short-term acute experimental diarrhea.

Cement Dust Exposure Alters Secretory Functions, Biochemical Profile and Morphology of Gastrointestinal Tissues in Rats Exposed to Cement Dust.

Asides direct gastrointestinal exposure, inhalation route is another major xenobiotic exposure pathway to the gastrointestinal tract via mucociliary escalator. This triphasic study assesses cement dust inhalatory exposure effect on the possible alterations of the gastrointestinal tissues and secretion. 72 male, sixteen (16) weeks old Wistar rats were randomized into 3 different phases of 24 animals. Each phase comprised of 3 group of 8 animals. Group 1 (control) were sham-operated with clean ambient air, group 2 (14-days exposed) were exposed to cement dust for 14days, and group 3 (28-day exposed) were exposed to cement dust for 28 days. Biochemical indices including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), sulfhydryl group, carbonyl group, Na+-K+ATPase pump activity, Nitric oxide (NO) were investigated spectrophotometrically in gastric and hepatic tissues while histopathology was studied using standard procedure. There was significant increase in the level of MDA, NO and carbonyl- an observation that contrasts with the level of CAT, SOD and sulfhydryl; no significant difference in Na+-K+-ATPase pump was observed in the exposed groups compared with control. Histopathological alterations in salivary gland and gastric tissues includes edema, inflammatory cell infiltration and vascular congestion. There was significant alteration in basal salivary, gastric and biliary secretions; increased stimulated salivary and gastric secretion via cholinergic stimulation. Conclusively, histopathological and spectrophotometric analyses reflect that inhalatory experimental exposure to cement dust significantly alter gastrointestinal secretions and predisposes the gastrointestinal tract to an array of deleterious effects via protein oxidation and antioxidant depletion and tissue peroxidation.

Potassium bromate (KBrO3) modulates oxidative stress and inflammatory biomarkers in sodium hydroxide (NaOH) - induced Crohn's colitis in Wistar rats.

Potassium bromate (KBrO3) present in consumed ozonised water was recently documented to exacerbate experimental gastric ulcer. Information, however, is vague as regards its effects in the colon where water reabsorption occurs. In this study, we observed the possible effects of KBrO3 on oxidative stress and inflammatory biomarkers in sodium hydroxide (NaOH) - induced Crohn's colitis (CC). Wistar rats (180-200 g) were divided into six groups (n = 10): (i) control; (ii) untreated CC (induced by 1.4% NaOH; intra-rectal administration); and (iii-vi) CC treated with vitamin E, KBrO3, vitamin E+KBrO3, and sulphazalazine, respectively, for 7 days. Body weight and stool score were monitored daily. By day 3 and 7, excised colon was evaluated for ulcer scores and biochemical and histological analysis. Blood samples collected on days 3 and 7 were assayed for haematological indices using standard methods. Data were subjected to analysis of variance (ANOVA) and p ≤ 0.05 considered significant. Platelet/lymphocyte ratio, colonic ulcer score, malondialdehyde, and mast cells were significantly decreased while colonic sulfhydryl, and Ca2+- and Na+/K+-ATPase activities were increased following KBrO3 treatment compared with untreated CC. These findings suggest that KBrO3 may mitigate against NaOH-induced CC via inhibiting mast cell population and oxidative and inflammatory content but stimulating colonic sulfhydryl and Ca2+- and Na+/K+-ATPase activities.

Biochemical and histopathological effects of low dose vanadium in the healing of acetic acid-induced colitis in male wistar rats.

OBJECTIVES: Vanadium has been reported to possess relevant therapeutic properties such as anti-diabetic and anti-tumoral. This study aimed at determining the effects of vanadium on experimentally induced colitis in rats. METHODS: Forty-five male Wistar rats (103 ± 3.90 g, n=15) were used for this study and were divided into three groups. Group 1 (Untreated control) had nothing added to their drinking, while groups 2 and 3 received sodium metavanadate at a dose of 50 and 200 mg/L respectively in their drinking water for 10 weeks. Colitis was thereafter induced by intra colonic administration of 1.50 mL of 6% acetic acid. Animals were sacrificed on day 0 (pre-induction), three- and seven-days post induction. Blood samples were collected for haematological variables and the distal 8 cm of the colon was collected for macroscopic, histological and biochemical (malondialdehyde-MDA, superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase- GPx and nitrite concentration- NO) assessment. RESULTS: Low dose vanadium proved beneficial in ameliorating acetic acid-induced colitis by improving both histopathological and haematological changes. Gross observation showed a faster healing rate in vanadium treated groups (50 and 200 mg/L) compared with untreated control at day 3 (40 and 26.20 vs. 2.50%) and day 7 (80 and 66.70 vs. 42%) respectively. Vanadium also appears to exert its beneficial effects on acetic acid-induced colitis via up regulation of antioxidant enzymes (SOD, CAT, GPx) and NO while decreasing the over production of MDA. CONCLUSIONS: Vanadium at small concentration functions as an essential trace element and may be able to promote healing process during ulcerative colitis.

Attenuation of ischemia-reperfusion-induced gastric ulcer by low-dose vanadium in male Wistar rats.

AIM: Vanadium, a trace element found in food and water sources has been previous reported to attenuate ulcer formation without much insight into its mechanism of action. This study highlights the mechanism by which vanadium exhibits its gastro-protective activity. MAIN METHODS: Eighty male Wistar rats (80-100 g) were randomized into 8 equal groups. Groups 1 (control) and 2 (Ulcerated control) received water only, groups 3-8 received vanadium at 5, 10, 25, 50, 100 and 200 ppm respectively in their drinking water for ten weeks. Gastric ulcer was thereafter induced in groups (2-8) via ischaemia-reperfusion (IR) technique. The stomachs were excised for macroscopic examination, evaluation of mucous content, oxidative stress markers, hydrogen/potassium (H+/K+) and calcium (Ca++) ATPases activities plus expression of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Vanadium at low doses inhibited IR induced gastric ulcer by 62.62% (10 ppm), 54.80% (25 ppm) and 43.50% (50 ppm). KEY FINDINGS: Low dose vanadium increased mucous content, superoxide dismutase, catalase, glutathione activities and nitrite concentrations compared to ulcerated control group. The observed increase in malondialdehyde, Ca++ and H+/K+ ATPase activities, iNOS and COX-2 expression following IR were significantly reduced by pretreatment with vanadium. SIGNIFICANCE: This study demonstrated that vanadium at low doses exhibit gastro-protective activities on IR induced gastric ulcer in rat model by inhibiting proton pump activities and decreasing expressions of iNOS and COX-2, thereby giving more insight into the protective action of vanadium.

Dose-dependent changes in Haematological and Serum Biochemical Variables in Rats Exposed to Sodium Metavandate in Male Wistar Rats.

The interest in the role of vanadium compounds in living organisms has grown tremendously especially since the report of its glycemic normalization activity in the 1980s. There has been reports of both its toxic as well as positive effects, thus there is a paucity of information on the essentiality of this element in biological systems. In this study, the effect of different doses of sodium metavanadate on the haematological and biochemical variables of male Wistar rats was investigated.  Twenty male Wistar rats were divided into four groups of five each and were given tap water containing various concentrations of sodium metavanadate (0ppm- group 1, 50ppm- group 2, 100ppm- group 3, or 200ppm- group 4) for 10weeks. Weekly body changes were noted and blood was collected at the end of 10 weeks by retro orbital puncture for haematological and serum biochemical variables. Histological sections were also performed on liver and kidney tissues. There was a significant increase in body weight in the 50ppm group compared with control. Sodium metavanadate at 200ppm caused a significant decrease in packed cell volume (PCV), red blood cell count (RBC), white blood cell count (WBC) and Lymphocytes with significant increases in neutrophils and neutrophil-lymphocyte ratio when compared with control values. There was also a significant decrease in ALP, ALT and a significant increase in urea concentration in the 200ppm group when compared with control values. All doses of sodium metavanadate significantly reduced blood glucose level. Sections of liver and kidney revealed severed damage at 200ppm compared with control. The results from this study showed that vanadium affects both haematological and biochemical parameters and could be toxic at higher concentrations, while at low concentration could be beneficial as seen with the enhanced body weight.

Thyroid hormones increase stomach goblet cell numbers and mucin expression during indomethacin induced ulcer healing in Wistar rats.

BACKGROUND: Gastric ulcers are mucosal discontinuities that may extend into the mucosa, submucosa or even deeper. They result from an imbalance between mucosal aggressors and protective mechanisms that include the mucus bicarbonate layer. Thyroid hormones have been shown to accelerate gastric ulcer healing in part by increasing the adherent mucus levels. However, the effects of thyroid hormones on goblet cell numbers and expression of neutral and acidic mucins during ulcer healing have not been investigated. METHODS: Thirty six adult male Wistar rats were randomly divided into six groups each with six animals. Group 1 (normal control) and group 2 (negative control) were given normal saline for eight weeks. Groups 3 and 4 were given 100 µg/kg per day per os of thyroxine so as to induce hyperthyroidism. Groups 5 and 6 received 0.01% (w/v) Propylthiouracil (PTU) for 8 weeks so as to induce hypothyroidism. After thyroid hormonal levels were confirmed using radioimmunoassay and immunoradiometric assays, ulcer induction was done using 40 mg/kg intragastric single dose of Indomethacin in groups 2, 3 and 5. Stomachs were extracted after day 3 and 7 of ulcer induction for histological examination. Histochemistry was carried out using Periodic Acid Shiff and Alcian Blue. The number of acidic and neutral goblet cells were determined by counting numbers per field. Mucin expression (%) was determined using Quick Photo Industrial software version 3.1. RESULTS: The numbers of neutral goblet cells (cells/field) increased significantly (P < 0.05) in the ulcer+thyroxine (14.67 ± 0.33), thyroxine (17.04 ± 1.71) and ulcer+PTU (12.89 ± 1.06) groups compared to the normal control (10.78 ± 1.07) at day 3. For the acidic goblet cells, differences between treatment groups were more pronounced at day 7 between the ulcer+thyroxine (22.56 ± 1.26) and thyroxine (22.89 ± 0.80). We further showed that percentage expression of both neutral and acidic mucins was significantly higher in the ulcer+thyroxine (9.23 ± 0.17 and 6.57 ± 0.35 respectively) and thyroxine groups (9.66 ± 0.21 and 6.33 ± 0.38 respectively) as compared to the normal control group (4.08 ± 0.20 and 4.38 ± 0.11 respectively) at day 3 after ulcer induction. CONCLUSION: This study confirms the role played by thyroid hormones in healing of indomethacin induced gastric ulcers. The study further demonstrates increased numbers of both neutral and acidic goblet cells and the increase in expression of both neutral and acidic mucins during healing of indomethacin induced ulcers.

Kolaviron attenuates ischemia/reperfusion injury in the stomach of rats.

Kolaviron (KV), an active complex of at least 3 compounds in Garcinia kola seed, which is known for its antioxidant and anti-inflammatory activity, was investigated for its gastro-protective effect in the stomach of rats subjected to ischemia/reperfusion-induced gastric ulceration. Male adult Wistar rats (180-210 g) were randomized into 6 groups (n = 15) as follows: (i) control, (ii) ulcerated untreated (UU), (iii) KV alone (KVA), (iv) KV + ulcer (KVU), (v) ulcer + KV (UKV), and (vi) ulcer + omeprazole (20 mg/kg). Ulcer was induced through ischemia/reperfusion method after 2 weeks of daily oral KV (100 mg/kg). Rats were weighed daily, and gastric acid secretion, ulcer scores, hematological, biochemical, and histological variables were assessed 1 h after induction at 3 and 7 days post-ulceration. Body weight decreased in KVA (179.1 ± 1.6 g), and KVU (170.1 ± 2.2 g) compared with UU (199.0 ± 1.4 g). Gastric acid secretion decreased significantly in KVU after 1 h and 3 days post-ulceration (0.27 ± 0.03 mEq/L; 0.49 ± 0.02 mEq/L) compared with UU (0.60 ± 0.06 mEq/L; 0.85 ± 0.29 mEq/L), respectively. There was significant reduction in neutrophil/lymphocyte ratio of KVA (0.29 ± 0.06) and KVU (0.35 ± 0.02) compared with UU (0.54 ± 0.04). Malondialdehyde level decreased significantly with concomitant increase in anti-oxidative activities and nitric oxide level in the KV treated groups (KVA, KVU, UKV) compared with UU. In conclusion, treatment with KV protects the stomach by reducing gastric acid secretion, promoting antioxidant activity and suppressing action of reactive oxygen species.

Seeds of Buchholzia coriacea in Diet Mitigate Ischemic Reperfusion-Induced Gastric Ulceration in Experimental Rats.

Buchholzia coriacea (B. coriacea) seeds, in folk medicine, have been documented to prevent gastric ulceration though the mechanism is not fully elucidated. To clarify this, the gastro-healing activities were investigated using graded incorporation of B. coriacea seeds in the diet. Male Wistar rats (150-200 g) were divided into 7 groups (n = 15): unulcerated untreated control, ulcerated untreated control, unulcerated B. coriacea low (10%), ulcerated B. coriacea low (10%), nulcerated B. coriacea high (25%), ulcerated B. coriacea high (25%), and ulcerated omeprazole-treated groups. Rats were fed with B. coriacea diets for 7 weeks; thereafter, ulcer was induced by ischemic reperfusion method. Daily body weight, gastric acid secretion, hematological parameters, stomach ulcer score, and biochemical and histological analyses were evaluated on days 0, 3, and 7 post-ulcer induction. Results were subjected to one-way analysis of variance (ANOVA) and presented as mean ± standard error of the mean (SEM); p ≤.05 was considered significant. Significant decreases were observed in mean body weight of B. coriacea-fed compared with control and omeprazole-treated groups from week 7. Ulcerated B. coriacea-fed showed significant decrease in gastric acid secretion by days 3 and 7 compared with ulcerated control groups. Malondialdehyde content was significantly decreased in ulcerated B. coriacea-fed compared with control and omeprazole-treated groups. Significant increases in hematological variables (notably platelet count), superoxide dismutase, catalase, and nitric oxide levels of B. coriacea-fed compared with control and omeprazole-treated groups by days 0 and 3 were observed. Histological evaluations further confirmed these observations. B. coriacea diet enhanced gastric healing activities on ischemic reperfused gastric ulcer. Increased platelet count and nitric oxide levels may play significant roles in this process.

Effects of quinine on gastric ulcer healing in Wistar rats.

Background Quinine (QT) is an important anti-malarial drug; however, there is little information about its effects on the gut. Therefore, this study aimed to investigate the effects of a therapeutic dose of QT on the healing of gastric ulcer in rats. Methods Male Wistar rats weighing 150-200 g were divided into three groups: control rats without ulcer (group 1), ulcerated rats treated with 1 mL/kg (p.o.) normal saline (NS) (group 2), and ulcerated rats treated with 10 mg/kg (p.o.) QT (group 3). Ulcers were induced by serosal application of 80 % acetic acid to the stomach of rats anaesthetized with 50 mg/kg thiopentone sodium and treatment was given three times daily. Healing was assessed on days 3, 7 and 10 after ulcer induction by macroscopic measurement of: ulcer area, histology, lipid peroxidation, superoxide dismutase activity and gastric mucus secretion. Results At day 3, there was no significant difference (p>0.05) in ulcer areas between NS- and QT-treated rats. By day 10, however, the percentage area healed in NS treated (59.6±2.35 %) was significantly higher (p<0.05) than in QT rats (49.0±2.20 %) and clearing of inflammatory cells and re-epithelization was greater in NS-treated group. By days 7 and 10, lipid peroxidation was significantly higher in QT animals, when compared with NS-treated rats and controls (p<0.05). Superoxide dismutase activity and mucus secretion were significantly (p<0.05) higher in NS-treated than QT-treated rats. Conclusions QT delayed ulcer healing by prolonging the inflammatory phase of healing, increasing oxidative stress, reducing antioxidant activity and gastric mucus secretion.

Lead exposure increases oxidative stress in the gastric mucosa of HCl/ethanol-exposed rats.

AIM: To investigate the role of reactive oxygen species in the ulcer-aggravating effect of lead in albino rats. METHODS: Albino Wistar rats were randomly divided into three groups and treated orally with 100 mg/L (low dose) or 5000 mg/L (high dose) of lead acetate for 15 wk. A third group received saline and served as control. At the end of wk 15, colorimetric assays were applied to determine the concentrations of total protein and nitrite, the activities of the oxidative enzymes catalase and superoxide dismutase, and lipid peroxidation in homogenized gastric mucosal samples. RESULTS: Exposure of rats to lead significantly increased the gastric mucosal damage caused by acidified ethanol. Although the basal gastric acid secretory rate was not significantly altered, the maximal response of the stomach to histamine was significantly higher in the lead-exposed animals than in the unexposed control group. Exposure to low and high levels of lead significantly increased gastric lipid peroxidation to 183.2%+/-12.7% and 226.1%+/-6.8% of control values respectively (P<0.0). On the other hand, lead exposure significantly decreased catalase and superoxide dismutase (SOD) activities and the amount of nitrite in gastric mucosal samples. CONCLUSION: Lead increases the formation of gastric ulcers by interfering with the oxidative metabolism in the stomach.