Abstract
Constipation due to colonic contractility disorders is the predominant gastrointestinal symptom in diabetics. Hydrogen sulfide (H2S) 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 H2S. This study investigated the effects of H2S 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. H2S 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. H2S inhibition decreased CBS and CSE gene expression, and improved SRB levels, ITR, and histological factors. The results of this study demonstrated that H2S is an effective and key factor in regulating colonic motility in mice with DC. In the future, inhibitors of H2S production may be used to manage the digestive complications associated with DC.
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The datasets used and/or analyzed during the current study available from the first author, Razieh Kazemzadeh, on reasonable request. Gmail: kazemzadehrazieh@gmail.com.
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Funding
This paper is a part of Razieh Kazemzadeh’s Ph.D. thesis. This work is financially supported by the Persian Gulf Physiology Research Center of Ahvaz Jundishapur University of Medical Sciences (Grant No. APRC-0203).
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All authors contributed to the study conception and design. Material preparation was performed by SA.M. and M.B. Data collection and analysis were performed by R.K. and F.S. M.S and A.A contributed to the practical work. A.R contributed to histological analysis and manuscript writing. The first draft of the manuscript was written by R.K. and SA.M, and all authors collaborated on the final writing and editing of the manuscript. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Kazemzadeh, R., Badavi, M., Rezaie, A. et al. Pharmacological inhibition of hydrogen sulfide production mitigates constipation in a type 1 diabetes mouse model. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38664-8
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DOI: https://doi.org/10.1038/s41598-026-38664-8
