Pathophysiological role of ion channels and transporters in gastrointestinal mucosal diseases

The incidence of gastrointestinal (GI) mucosal diseases, including various types of gastritis, ulcers, inflammatory bowel disease and GI cancer, is increasing. Therefore, it is necessary to identify new therapeutic targets. Ion channels/transporters are located on cell membranes, and tight junctions (TJs) affect acid–base balance, the mucus layer, permeability, the microbiota and mucosal blood flow, which are essential for maintaining GI mucosal integrity. As ion channel/transporter dysfunction results in various GI mucosal diseases, this review focuses on understanding the contribution of ion channels/transporters to protecting the GI mucosal barrier and the relationship between GI mucosal disease and ion channels/transporters, including Cl−/HCO3− exchangers, Cl− channels, aquaporins, Na+/H+ exchangers, and K+ channels. Here, we provide novel prospects for the treatment of GI mucosal diseases.

Gastric mucosal function in portal hypertensive gastropathy secondary to schistosomal hepatic fibrosis: effect of sclerotherapy

Gastric mucosal function in portal hypertensive gastropathy secondary to schistosomal hepatic fibrosis [SHF] was evaluated. Group I comprised 20 patients with no bleeding;10 had portal hypertensive gastropathy [PHG]. Group II comprised 20 patients with bleeding. Free acidity, total acidity, basal acid output, serum pepsinogen I, gastric mucosal blood flow [GMBF] and gastrin were significantly lower in group II, whereas serum gastrin and somatostatin staining were significantly higher. No histopathological changes were noted between both groups, In conclusion, bleeding caused by SHF results in hypoacidity, hypergastrinaemia and hypopepsinogenaemia. Estimated GMBF distinguishes patients with PHG and those who are bleeders

Mucosal blood flow in the remaining rectal stump is more affected by total than partial mesorectal excision in patients undergoing anterior resection: a key to understanding differing rates of anastomotic leakage?

Purpose Anterior resection is the procedure of choice for tumours in the mid and upper rectum. Depending on tumour height, a total mesorectal excision (TME) or partial mesorectal excision (PME) can be performed. Low anastomoses in particular have a high risk of developing anastomotic leakage, which might be explained by blood perfusion compromise. A pilot study indicated a worse blood flow in TME patients in an open setting. The aim of this study was to further evaluate perianastomotic blood perfusion changes in relation to TME and PME in a predominantly laparoscopic context. Method In this prospective cohort study, laser Doppler flowmetry was used to evaluate the perianastomotic colonic and rectal perfusion before and after surgery. The two surgical techniques were compared in terms of mean differences of perfusion units using a repeated measures ANOVA design, which also enabled interaction analyses between type of mesorectal excision and location of measurement. Anastomotic leakage until 90 days after surgery was reported for descriptive purposes. Results Some 28 patients were available for analysis: 17 TME and 11 PME patients. TME patients had a reduced blood perfusion postoperatively compared to PME patients in the aboral posterior area (mean difference: −57 vs 18 perfusion units; p = 0.010). An interaction between mesorectal excision type and anterior/posterior location was detected at the aboral level (p = 0.007). Two patients developed a minor leakage, diagnosed after discharge. Conclusion Patients operated on using TME have a decreased blood flow in the aboral posterior quadrant of the rectum postoperatively compared to patients operated on using PME. This might explain differing rates of anastomotic leakage. Trial registration ClinicalTrials.gov Identifier: NCT02401100

A Study of Antiulcer Activity in Cynodon dactylon Leaves Extract on Albino Rats

Peptic ulcer is a chronic, non-malignant inflammatory disease characterized by ulceration in the upper gastro-intestinal tract (stomach and duodenum) where parietal cells are found. The aetiology of gastric ulceration is multifactorial and not clearly defined, but some predisposing factors have been implicated. This includes duration of starvation, nature of food ingested, bile reflux, lessened mucosal resistance, alteration of gastric mucosal blood flow, disruption of gastric mucosal barrier by stress, decrease in alkaline mucosal bicarbonate and mucus secretion, over dosage and or prolonged administration of non-steroidal anti-inflammatory drugs. Among numerous species of plants growing in India, Durva or taxonomically the Cynodon dactylon occupies a key position in ethno medicinal practices and traditional medical knowledge systems (Ayurveda, Unani, Nepalese, and Chinese). Durva consists of dried whole plant of Cynodon dactylon (Linn.) Pers. (Family: Poaceae), an elegant, tenacious, perennial, creeping grass growing throughout the country. In our present study, the mature green leaves of Cynodon dactylon belongs to family Poaceae were collected from in and around area of Thanjavur District, Tamil Nadu, South India. The plant was identified with the help of Manual of Tamil Nadu and Karnatic flora with standard references. From this study, it is clear that C. dactylon leaf extract has significant anti-ulcer activity in animal models. The extract is non-toxic even at relatively high concentrations. The anti-ulcer activity is probably due to the presence of flavonoids.

Gastroprotective effect of the root extract of Alpinia officinarum Hance (Zingiberoside) against acute indomethacin-induced gastric injuries in rats: Involvement of H+/K+-ATPase and prostaglandin E receptors

Purpose: To investigate the protective effects of Alpinia officinarum root ethanol extract (AOE) and galangin against acute indomethacin-induced injury on rat gastric mucosaMethods: Sprague-Dawley rats were daily treated with bismuth potassium citrate (0.08 g/kg), AOE at doses of 0.09, 0.18 and 0.36 g/kg; and galangin (0.2 g/kg) for 15 days. Then, gastric injury on rats was induced by intragastric administration of indomethacin (30 mg/kg). Blood flow and thickness of gastric mucosa were determined using neutral red clearance test and Alcian blue staining. The activity of H+/K+-ATPase was assayed using a biochemical kit. Prostaglandin E receptor expressions were assayed by western blotting.Results: High doses of ethanol extract of Alpinia officinarum root significantly inhibited H+/K+-ATPase activity by 8.12 % (p < 0.01), increased gastric mucosal blood flow (p < 0.001), enhanced mucus thickness (p < 0.05), and elevated the activities of prostaglandin E receptors 1 and 4 (p < 0.05).Galangin significantly inhibited H+/K+-ATPase activity by 4.82 % (p < 0.05) and increased gastric mucosal blood flow (p < 0.01).Conclusion: The ethanol extract of Alpinia officinarum root attenuates indomethacin-induced gastric injury by reinforcing gastric mucosal barrier and inhibiting excessive gastric acid secretion. Thus, the extract can be potentially developed for management of gastric injuries. Keywords: Galangin, Gastric mucosal barrier, Gastric acid, Prostaglandin, Indomethacin

Protective Effects of Wheat Peptides against Ethanol-Induced Gastric Mucosal Lesions in Rats: Vasodilation and Anti-Inflammation

Alcohol consumption increases the risk of gastritis and gastric ulcer. Nutritional alternatives are considered for relieving the progression of gastric mucosal lesions instead of conventional drugs that produce side effects. This study was designed to evaluate the gastroprotective effects and investigate the defensive mechanisms of wheat peptides against ethanol-induced acute gastric mucosal injury in rats. Sixty male Sprague–Dawley rats were divided into six groups and orally treated with wheat peptides (0.1, 0.2, 0.4 g/kgbw) and omeprazole (20 mg/kgbw) for 4 weeks, following absolute ethanol administration for 1 h. Pretreatment with wheat peptides obviously enhanced the vasodilation of gastric mucosal blood vessels via improving the gastric mucosal blood flow and elevating the defensive factors nitric oxide (NO) and prostaglandin E2 (PGE2), and lowering the level of vasoconstrictor factor endothelin (ET)-1. Wheat peptides exhibited anti-inflammatory reaction through decreasing inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, and increasing trefoil factor 1 (TFF1) levels. Moreover, wheat peptides significantly down-regulated the expression of phosphorylated nuclear factor kappa-B (p-NF-κB) p65 proteins in the NF-κB signaling pathway. Altogether, wheat peptides protect gastric mucosa from ethanol-induced lesions in rats via improving the gastric microcirculation and inhibiting inflammation mediated by the NF-κB signaling transduction pathway.

The effect of apelin-13 on gastric ischemia/reperfusion injury: the roles of sensory nerves and vagus nerve

Apelin is a peptide that plays a role in physiological processes such as angiogenesis, apoptosis, and proliferation. The aim of this study was to investigate the role of capsaicin-sensitive afferent neurons and vagus in the effect of apelin against ischemia/reperfusion (I/R) injury. The experimental groups were (1) control, (2) I/R, (3) apelin + I/R, (4) vagotomy + I/R, (5) vagotomy + apelin + I/R, (6) capsaicin + I/R, (7) capsaicin + apelin + I/R, (8) lorglumide + I/R, and (9) lorglumide + apelin + I/R. To test the potential gastroprotective effect of apelin-13, apelin-13 (2 mg/kg i.v.) was administered just before both ischemia and reperfusion. A vagotomy was performed 1 week before I/R in the vagotomized groups; capsaicin (125 mg/kg s.c.) was administrated 2 weeks before I/R in the capsaicin-treated groups and lorglumide (5 mg/kg i.p.) was administered 30 min before I/R in the lorglumide-treated groups. After I/R, a variety parameters in gastric tissue were analyzed. cfos expression was determined in brainstem samples. In the I/R group, the lesion index, myeloperoxidase activity, lipid peroxidation, nitric oxide, and tumor necrosis factor-α increased, and mucosal blood flow, prostaglandin-E2, and calcitonin gene related peptide decreased. Apelin prevented the damaging effects of I/R and increased cfos expression in brainstem areas. Vagotomy, capsaicin, and lorglumide largely eliminated the gastroprotective effects of apelin-13. This study showed that sensory nerves and the vagus play regulatory roles in apelin-induced gastroprotection. Cholecystokinin may play a role in the effect of apelin through sensory neurons.

Electroacupuncture Improves the Survival Rate and Organ Function in a Rat Model of Hemorrhagic Shock

Electroacupuncture (EA) at ST36 can improve the survival rate in rats after hemorrhagic shock (HS). The current study investigated rats with 60% blood loss. 144 rats were divided into four groups: hemorrhage without fluid resuscitation (HS), EA after hemorrhage without fluid resuscitation (EA), hemorrhage with delayed resuscitation (DFR), and EA after hemorrhage with delayed resuscitation (EA + DFR). The survival rate and biological parameters 0, 3, 12, and 24 h after HS were investigated. The 24 h survival rate of EA + DFR was significantly higher than that of DFR. 12 h after hemorrhage, the level of mean arterial blood pressure of EA + DFR was significantly higher than that of DFR, and the levels of renal blood flow, intestinal mucosal blood flow, and hepatic blood flow of EA + DFR were also significantly higher than those of DFR. Three hours after hemorrhage, the levels of lactate, PaCO2, alanine aminotransferase, and creatinine of groups receiving EA were significantly lower than those of non-EA groups, and the levels of pH, PaO2, and diamine oxidase of groups receiving EA were significantly higher. EA at ST36 can improve the 24 h survival rate and produce the experimental antishock effects on tissue perfusion and organ protection from fatal HS.

Weiqi Decoction Attenuated Chronic Atrophic Gastritis with Precancerous Lesion through Regulating Microcirculation Disturbance and HIF-1α Signaling Pathway

Aim. Chronic atrophic gastritis (CAG), the precancerous lesions of gastric cancer, plays an important role in the stepwise process of gastric cancer. The ancient Chinese medicine believes in that Qi deficiency and blood stasis are involved in the pathogenesis of CAG. Weiqi decoction, a classical formula from Longhua Hospital, could supplement Qi and activate blood circulation of human beings and has been used for treating CAG in clinic over twenty years. The study aims to clarify the effect and underlying molecular mechanism of Weiqi decoction on CAG rats. Methods. Forty-eight male Wistar rats were divided randomly into six groups: control group, model group, folic acid group, and WQD-treated groups at doses of 4 g/kg, 2 g/kg, and 1 g/kg, with eight rats in each group. MNNG and saturated NaCl were used to induce CAG rat with precancerous lesion (intestinal metaplasia and dysplasia). After 40 weeks, gastric mucosal blood flow was measured using Laser Doppler Flowmetry. The pathological changes of the gastric mucosa were identified by H&E staining and AB-PAS staining. The protein expression of COX-2, HIF-1α, VEGFR1, VEGFR2, Ki67, and cleaved caspase 3 in the gastric tissues was measured by western blotting approach. Gene expression of COX-2, HIF-1α, VEGF, VEGFR1, VEGFR2, Ang-1, and Ang-2 was detected by using Quantitative PCR method. The PGE2 concentrations in serum were detected by ELISA method. The protein expression of Ki67 in gastric mucosa was also detected by immunohistochemistry. Results. Compared with control rats, atrophy and intestinal metaplasia as well as the microcirculation disturbance of gastric mucosa were induced in the stomach of CAG rats identified by the H&E and AB-PAS staining as well as microcirculation measurement, which could be significantly attenuated by WQD treatment. Moreover, compared with the control group, the protein and gene expression of COX-2, HIF-1α, VEGFR1, and VEGFR2 in gastric tissues of pylorus was obviously increased and the serum PGE2 level was significantly deceased in CAG rats, which could be significantly counteracted by WQD administration. However, the gene expression of Ang-1 and Ang-2 was not significant difference between control rats and CAG rats, and WQD also had no significant effect on the gene expression of Ang-1 and Ang-2. Furthermore, the increased cell proliferation marked by upregulated protein expression of Ki67 and decreased cell apoptosis marked by downregulated protein expression of cleaved caspase 3 in stomach of pylorus in CAG rats were obviously reversed by WQD treatment. Conclusion. WQD attenuated CAG with precancerous lesion through regulating gastric mucosal blood flow disturbance and HIF-1α signaling pathway.