Pharmacological inhibition of hydrogen sulfide production mitigates constipation in a type 1 diabetes mouse model.

Abstract

Constipation due to colonic contractility disorders is the predominant gastrointestinal symptom in diabetics. Hydrogen sulfide (HS) is an intestinal contractile agent at low concentrations and a relaxant at high concentrations. Cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and sulfate-reducing bacteria (SRB) are among the factors that produce HS. This study investigated the effects of HS production inhibitors on colonic motility indices in mice with diabetic-induced constipation. Fifty-six mice were randomly allocated into four groups, including control, diabetic constipation (DC), disulfiram, and propargylglycine (PAG). Diabetes was induced using streptozotocin (STZ), followed by the administration of disulfiram and PAG. Blood and colon tissue samples were collected for analysis at the end of the study period. Measurements included body weight, blood glucose level, fecal parameters, and intestinal transit ratio (ITR). The gene expression levels of CBS, CSE, Bcl-2 antagonist/killer (BAK), and B-cell lymphoma 2 (BCL2) were measured, along with myosin light chain (MLC) protein expression. HS and gastrin levels, as well as the SRB content, were analyzed. Additionally, acetylcholinesterase (AChE) expression in colon tissue was evaluated. Histological assessment of the colon was also performed. Disulfiram and PAG administration improved the fecal pellet number and water content in mice with DC. HS inhibition decreased CBS and CSE gene expression, and improved SRB levels, ITR, and histological factors. The results of this study demonstrated that HS is an effective and key factor in regulating colonic motility in mice with DC. In the future, inhibitors of HS production may be used to manage the digestive complications associated with DC.