Decreased mRNA Expression of Cystathionine Gamma lyase and H2S Concentration in Gastric Mucosal Tissue in Diabetic Rats

Abstract

Background and aim: It is well established that the rate of gastric lesions increases in diabetic rats. Recently, the protective effect of hydrogen sulfide (H2S) in gastric mucosa has been proven. This study aimed to determine the release of H2S and mRNA expression of cystathionine gamma lyase (CSE) in gastric mucosa in alloxan-diabetic rats in response to distention-induced gastric acid secretion. Twenty-four rats were randomly assigned to 4 groups (6 in each). They were the normal-control, distention-control, diabetic-control, and distention-diabetic groups. Under anesthesia, animals underwent a tracheotomy and midline laparotomy. To washout the gastric contents, a catheter was inserted in the stomach through the duodenum. To determine the effect of distention-induced gastric acid secretion on H2S release and mRNA expression of CSE, the stomachs were distended by normal saline. At the end of experiments, animals were sacrificed and the gastric mucosa was collected to determine H2S concentration and to quantify mRNA expression of CSE by quantitative realtime PCR. Mucosal release of H2S and mRNA expression of CSE significantly increased in response to stimulated gastric acid secretion in normal rats (P<0.01), while the increases in diabetic rats were not significant. Basal release of H2S and mRNA expression of CSE in gastric mucosa were significantly in diabetic rats lower than normal rats. On the basis of the results, we conclude that the decreased release of H2S in response to basal and stimulated gastric acid output in alloxan-diabetic rats compared to normal rats is largely due to downregulation of mRNA expression of CSE.

Antidiarrheal effect of sodium hydrosulfide in diabetic rats: In vitro and in vivo studies

“…Analysis of qRT‐PCR results showed that mRNA expressions of CSE, and CBS in smooth muscles of jejunum, ileum, and colon in diabetic rats decreased compared to normal rats. In agreement, the authors recently have shown that the mRNA expression of CSE decreased in gastric mucosa, and muscles in alloxan‐induced diabetic rats . In a previous study, Yamane et al.…”

“…These findings together concluded that endogenous production of H 2 S decreased in diabetic rats. However, in this study we did not directly measure the tissue level of H 2 S but our previous research showed that in addition to mRNA, tissue level of H 2 S in gastric mucosa decreased in diabetic rats . Moreover, the authors recently have been shown that there is a direct correlation between expression level of protein and mRNA of CSE .…”

“…In agreement, the authors recently have shown that the mRNA expression of CSE decreased in gastric mucosa, and muscles in alloxan-induced diabetic rats. 4,7 In a previous study, Yamane et al showed that pharmacologically inhibition of CBS, and CSE stimulates the contraction of ileum in mouse. 10 Moreover, it has been shown that the level of protein expression of CBS, and CSE in lower esophageal sphincter in patient with achalasia decreases which implied that hydrogen sulfide involved in the pathophysiology of this disease.…”

“…The prevalence of diabetic diarrhea in diabetic patients is 20%. The fecal incontinence and anorectal dysfunction may be due to autonomic neuropathy, bacterial overgrowth, medications, and dietary factors …”

“…The fecal incontinence and anorectal dysfunction may be due to autonomic neuropathy, bacterial overgrowth, medications, and dietary factors. [1][2][3][4] In vitro studies have been shown that H 2 S decrease the frequency and tension of spontaneous contractions of the smooth muscles of gastric fundus, 5 jejunum and colon in rat, mouse and human. 6 A recent report by authors showed that H 2 S is involved in the pathophysiology of diabetic gastroparesis.…”