Sucralfate Protects Intestinal Epithelial Cells from Radiation-Induced Apoptosis in Rats

Abstract

Radiotherapy for malignant pelvic disease is often followed by acute radiation colitis (ARC). It has been reported that sucralfate treatment has a protective effect against ARC, though the mechanisms of action are unknown. The effects of sucralfate on X-ray radiation-induced apoptosis was studied at 4 Gy in the colonic crypt cells of rats. Sucralfate enemas given prior to radiation resulted in the following: (1) reduction in number of apoptotic colonic crypt cells; (2) reduction in number of caspase-3 positive cells; (3) decreases in p53 accumulation and p21 expression; (4) decreases of Bax/Bcl-2 ratio. The protective effects of sucralfate against ARC may be partially due to the suppression of radiation-induced apoptosis by way of p53 in the colon and the protection of the colonic epithelial stem cell region.

Evaluation of the application of enemas containing sucralfate in tissue content of neutral and acid mucins in experimental model of diversion colitis

“…Recent research has also demonstrated that shortages of SCFAs greatly reduces the expression of the MUC-2 gene, which is the main agent responsible for transcription of the protein fraction of colon mucins 8,30 . SCF is a cytoprotective agent that has been used for more than three decades in the treatment of several disorders such gastritis, duodenal, stress ulcers, burns, skin lesions, and DII [14][15][16][17][18]32 . SCF does not have any adverse effects and it's use is known to have multiple beneficial effects on mucocutaneous wound healing, because the drug can induce the proliferation of dermal fibroblasts, and limiting the inflammation might decrease fibrosis formation and EGF expression as well as the expression of other factors involved in tissue repair processes 32,33 .…”

“…Stimulating effects on vascular factors, such as angiogenesis, which play important roles in tissue repair, have been demonstrated by SCF 14,35 . The substance is a sucrose and sulfate-aluminum complex which, when in contact with gastrointestinal secretions, forms a viscous gel that adheres to the mucosa creating a physical barrier that protects the mucosa [15][16][17][18] . The complex formed, in addition to preventing the degradation of the mucus that covers the gastrointestinal epithelium has antimicrobial properties 31,36 .…”

“…Kochhar et al 16 were the first author to demonstrate the efficacy of enemas containing SCF in control of rectal bleeding due to radiation proctitis (RP). Since then, a string of well-conducted studies have confirmed the beneficial therapeutic effects of the substance in clinical, endoscopic and histological improvement in patients with RP, as well as in other forms of IBD where occur the formation of ulcers in the colonic mucosa, such as UC and solitary rectal ulcer 17,18 . Despite the DC course with the formation of superficial epithelial ulcerations and aphthous ulcers in the colonic mucosa, to the best of our knowledge, the effects of SCF on tissue expression of mucins has not yet been evaluated in patients or experimental models of DC.…”

Recent advances in the management of radiation colitis

“…Sucralfate enemas prior to radiation lead to reduction in: (a) the number of apoptotic colonic crypt cells; (b) the number of caspase-3 positive cells; (c) oncogene p53 accumulation and p21 expression; and (d) proapoptotic Bax/anti-apoptotic Bcl-2 ratio in rats. Therefore, the protective effects of sucralfate against radiation colitis might be partially due to the suppression of radiationinduced apoptosis in the colon and the protection of the colonic epithelial stem cell region [61] . Sucralfate administration may be also effective in human radiation proctocolitis [62] .…”

1,2,3,4,6-Penta-O-galloyl-.BETA.-D-glucose Protects Splenocytes against Radiation-Induced Apoptosis in Murine Splenocytes

“…23) Several studies have established that radiationinduced apoptosis is associated with the expression of p53-responsive protein in salivary gland 24) and hypoxic tumor cells. 25,26) In addition, it has been shown that synthetic and natural radioprotective agents such as amifostine, 27) sucralfate, 28) pentoxifylline, 29) and aloe polysaccharides 30) inhibit radiation-induced apoptosis by modulating the p53-dependent pathway. Detection of a change in the ratio of anti-to pro-apoptotic proteins such as Bcl-2 : Bax is important in confirming apoptosis.…”