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      Effect of bisacodyl on rats with slow transit constipation

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          Abstract

          The effect of bisacodyl on the treatment of rats with slow transit constipation (STC) was studied. Forty-five female Wister rats were divided into control group, STC group, and STC bisacodyl group. The immunohistochemical method was used to determine interstitial cells of Cajal (ICC) and the expression of c-Kit protein. Body mass and the number of defecations were significantly decreased in the STC group compared with the control group on the 100th day after diphenoxylate administration, while dry weight of feces was significantly increased and the intestinal transit time was prolonged. There were significant differences in the number of defecations, dry weight of feces, and intestinal transit time among the three groups. The number of defecations was higher, dry weight of feces was lower, and intestinal transit time was shorter in the STC bisacodyl group compared to the STC group. In addition, ICC basement membrane dissolution occurred in the colon wall of the STC group. The connection between ICC and surrounding cells was destroyed, and the nucleus shrunken to different degrees. Moreover, c-Kit expression in the STC group was significantly lower than the control group. The connection between ICC and surrounding cells in the STC bisacodyl group was significantly stronger than the STC group, and the number of ICC and the expression of c-Kit were increased. Bisacodyl could reduce the severity of STC in rats by increasing the number of ICC and the expression of c-Kit.

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          Most cited references20

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          The C-Kit Receptor-Mediated Signal Transduction and Tumor-Related Diseases

          As an important member of tyrosine kinase family, c-kit receptor causes specific expression of certain genes, regulates cell differentiation and proliferation, resists cell apoptosis, and plays a key role in tumor occurrence, development, migration and recurrence through activating the downstream signaling molecules following interaction with stem cell factor (SCF). The abnormality of SCF/c-kit signaling pathway is closely related to some certain tumors. The discovery of c-kit receptor-targeted drugs has promoted clinical-related cancer's diagnosis and treatment. In this paper, we review recent research progress on c-kit receptor-mediated signal transduction and its potential therapeutic application as a target in tumor-related diseases.
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            The laxative effect of bisacodyl is attributable to decreased aquaporin-3 expression in the colon induced by increased PGE2 secretion from macrophages.

            The purpose of this study was to investigate the role of aquaporin3 (AQP3) in the colon in the laxative effect of bisacodyl. After oral administration of bisacodyl to rats, AQP3, macrophages, cyclooxygenase 2 (COX2), and prostaglandin E(2) (PGE(2)) were examined in the colon. The mechanism by which bisacodyl decreases the expression of AQP3 was examined using HT-29 and Raw264.7 cells. When diarrhea occurred, a significant increase in the expression of PGE(2) and a decrease in AQP3 expression were observed. Immunostaining showed COX2 expression only in macrophages. The PGE(2) concentration increased significantly 30 min after the addition of bisacodyl to Raw264.7 cells. Thirty minutes after PGE(2) addition to HT-29 cells, the AQP3 expression level decreased to 40% of the control. When pretreated with indomethacin, bisacodyl did not induce an increase in the colon PGE(2) level, a decrease in the AQP3 expression level, or diarrhea. The results suggest that bisacodyl may decrease the expression of AQP3 in the colon, which inhibits water transfer from the luminal to the vascular side and leads to a laxative effect. This study also showed that direct activation of colon macrophages by bisacodyl increases the secretion of PGE(2), which acts as a paracrine factor and decreases AQP3 expression in colon mucosal epithelial cells.
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              Constipation: understanding mechanisms and management.

              Constipation is a frequently diagnosed gastrointestinal disorder. Symptoms of constipation are common, with the greatest prevalence in the elderly. Evaluation of constipation begins with a detailed medical history and a focused anorectal examination. Diagnostic testing for constipation is not routinely recommended in the initial evaluation in the absence of alarm signs. Key self-management strategies include increased exercise, a high-fiber diet, and toilet training. High-fiber diets can worsen symptoms in some patients who have chronic constipation. Biofeedback is an effective treatment option for patients who have constipation caused by outlet obstruction defecation. A variety of medications are available to remedy constipation.
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                Author and article information

                Journal
                Braz J Med Biol Res
                Braz. J. Med. Biol. Res
                bjmbr
                Brazilian Journal of Medical and Biological Research
                Associação Brasileira de Divulgação Científica
                0100-879X
                1414-431X
                28 May 2018
                2018
                : 51
                : 7
                : e7372
                Affiliations
                [1 ]Department of General Surgery, Pudong New Area People's Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China
                [2 ]Clinical Medical School, Shanghai University of Medicine & Health Sciences, Shanghai, China
                Author notes
                Correspondence: Xiao-hui Zhao: < zhaoxh99990@ 123456sina.com >
                Article
                00613
                10.1590/1414-431X20187372
                5995042
                29846410
                2a812e13-f14e-4435-9ec5-85457d0e4e9f

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 January 2018
                : 12 March 2018
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 20, Pages: 1
                Categories
                Research Articles

                bisacodyl,slow transit constipation,c-kit
                bisacodyl, slow transit constipation, c-kit

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