oxytocin and Stomach-Ulcer

This study aimed to apply transcriptomics to determine how Molor-Dabos-4 (MD-4) protects healthy rats against indomethacin (IND)-induced gastric ulcers and to identify the mechanism behind this protective effect. Rats were pretreated with MD-4 (0.3, 1.5, or 3 g/kg per day) for 21 days before inducing gastric ulcers by oral administration with indomethacin (30 mg/kg). Unulcerated and untreated healthy rats were used as controls. Effects of the treatment were assessed based on the ulcer index, histological and pathological examinations, and indicators of inflammation, which were determined by enzyme-linked immunosorbent assay. Transcriptomic analysis was performed for identifying potential pharmacological mechanisms. Eventually, after identifying potential target genes, the latter were validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). After pretreatment with MD-4, gastric ulcers, along with other histopathological features, were reduced. MD-4 significantly (p < 0.05) increased the superoxide dismutase (SOD) levels in ulcers and reduced pepsin, TNF-α, and IL-6 levels. RNA-seq analysis identified a number of target genes on which MD-4 could potentially act. Many of these genes were involved in pathways that were linked to anti-inflammatory and antioxidant responses, and other protective mechanisms for the gastric mucosa. qRT-PCR showed that altered expression of the selected genes, such as Srm, Ryr-1, Eno3, Prkag3, and Eef1a2, was consistent with the transcriptome results. MD-4 exerts protective effects against IND-induced gastric ulcers by reducing inflammatory cytokines and pepsin and increasing the expression of SOD levels. Downregulation of Srm, Ryr-1, Eno3, Prkag3, and Eef1a2 genes involved in regulating arginine and proline metabolism, calcium signaling pathway, HIF-1 signaling pathway, oxytocin signaling pathway, and legionellosis are possibly involved in MD-4-mediated protection against gastric ulcers.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arginine; Cytokines; Indomethacin; Interleukin-6; Medicine, Mongolian Traditional; Oxytocin; Pepsin A; Proline; Rats; RNA-Seq; Stomach Ulcer; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Oxytocin (OT) plays an important role in regulating gastric function. How OT regulates stress-induced gastric ulcers is not understood. We investigated OT's protective role in stress-induced gastric ulcers, with a focus on OT's interaction with the ventral tegmental area (VTA) to nucleus accumbens (NAc) dopamine pathway.. Drugs administration into the rats brain nuclei by brain stereotaxic apparatus, to examine related changes in gastric ulcer index, pH of gastric content, and mucus secretion, and to determine complex interactions between OT and DA systems in the regulation of stress and gastric functions.. Neurons in the VTA were co-immunoreactive for the OT receptor (OTR) and DA. In a rat model of stress-induced ulcer, water-immersion restricted stress, direct administration of OT into the VTA significantly reduced gastric ulcer index and increased the pH of gastric content and mucus secretion. OT's effects were eliminated by pretreatment with the OTR antagonist atosiban in the VTA and weakened with pretreatment of the DA D2 receptor (DA D2R) antagonist raclopride in the NAc. In OTR gene knockout (Oxtr. This study provides important data necessary for a deeper understanding of the complex interactions between OT and DA systems in the regulation of stress and gastric functions. It provides relevant mechanistic clues into OT's role as a protective factor against stress-induced changes to gastric function.

Topics: Animals; Dopamine; Dopamine Antagonists; Dopaminergic Neurons; Male; Mice; Mice, Knockout; Nucleus Accumbens; Oxytocin; Random Allocation; Rats; Rats, Wistar; Stereotaxic Techniques; Stomach Ulcer; Stress, Psychological; Vasotocin; Ventral Tegmental Area

To investigate the effect of centrally administered oxytocin and its receptor antagonist, atosiban, on gastric acid secretion and on experimentally induced gastric and duodenal ulcers.. The acute gastric ulcer models, such as pylorus ligation, indomethacin-induced and ethanol-induced gastric ulcers were used. Chronic gastric ulcers were induced by acetic acid and duodenal ulcers by cysteamine HCl.. In pylorus ligated rats, oxytocin (10 microg/kg, icv) showed significant antisecretory and antiulcer activity (P < 0.01). However, it aggravated the ethanol-induced gastric ulcers and did not show any effect on indomethacin-induced gastric ulcers. Oxytocin increased gastric ulcer healing in acetic acid-induced chronic gastric ulcers. The effect of oxytocin was reversed by atosiban (10 microg/kg, icv), a selective oxytocin receptor antagonist. Atosiban when given alone increased gastric acid secretion and ulcer index in pylorus-ligated rats and also aggravated acetic acid-induced chronic gastric ulcers. It seems the antiulcer activity of oxytocin was due to its anti-secretory effect.. Centrally administered oxytocin possesses gastric anti-secretory and anti-ulcer activity and oxytocin antagonist, atosiban, is pro-ulcerogenic in rats.

Topics: Animals; Anti-Ulcer Agents; Duodenal Ulcer; Female; Gastric Acid; Injections, Spinal; Male; Oxytocin; Pregnancy; Rats; Rats, Wistar; Receptors, Oxytocin; Stomach Ulcer; Vasotocin

The effect of oxytocin (1 mg/kg s.c) on gastric acid secretion and on different experimentally induced gastric and duodenal ulcers was studied. The acute gastric ulcer models used were pylorus ligation, indomethacin, ethanol and histamine induced acute gastric ulcers. Chronic gastric ulcers were induced using acetic acid and duodenal ulcers by cysteamine hydrochloride. Oxytocin showed significant antisecretory and antiulcer activity in pylorus ligated rats. Similarly oxytocin reduced the ulcer index in histamine induced gastric ulcers in guinea pigs and cysteamine induced duodenal ulcers in rats. The antiulcer and antisecretory effect was comparable to that of ranitidine (50mg/kg, i.p) though less in intensity. However, it did not show any gastric cytoprotective effect in ethanol and indomethacin induced ulcer models but ranitidine showed protection (p<0.05) in later model. Oxytocin enhanced gastric ulcer healing in acetic acid induced chronic gastric ulcer model. The reversal of oxytocin effect by atosiban, an oxytocin receptor antagonist indicates a role for oxytocin receptors. The antiulcer activity of oxytocin can be attributed to its antisecretory effect.

Topics: Acetic Acid; Acute Disease; Animals; Anti-Ulcer Agents; Chronic Disease; Cysteamine; Disease Models, Animal; Duodenal Ulcer; Duodenum; Ethanol; Female; Gastric Acid; Gastric Mucosa; Guinea Pigs; Histamine; Indomethacin; Male; Oxytocin; Pylorus; Ranitidine; Rats; Rats, Wistar; Stomach; Stomach Ulcer; Vasotocin

The effect of oxytocin has been studied in gastric lesions induced by cold-plus-restraint stress or by subcutaneous (sc) administration of cysteamine. Intracerebroventricular (icv) injection of the peptide was followed by a reduction of the incidence of gastric lesions in both experimental models. This effect was comparable to that found after icv injection of prolactin, a peptide which is known to facilitate adaptation to stress and reduce the incidence of stress-induced gastric lesions. These results may be relevant in focusing on the general role of oxytocin as a protective factor against stress-induced biological modifications.

Topics: Animals; Male; Oxytocin; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Stress, Physiological; Stress, Psychological