Mechanism of Asbt (Slc10a2)-related bile acid malabsorption in diarrhea after pelvic radiation.

Background: Radiation is a mode of treatment for many pelvic malignancies, most of which originate in the gynecologic, gastrointestinal, and genitourinary systems. However, the healthy gut is unavoidably included in the irradiation volume, resulting in undesirable results that manifest as radiation-induced diarrhea (RID), which is the most common side effect of radiation therapy and significantly affects the patients' quality of life. This study aimed to investigate the potential mechanism of diarrhea after pelvic radiotherapy in rats based on the effect of radiation on bile acid homeostasis and sodium-dependent bile acid transporter (Asbt).Methods: In this experimental study, male Sprague-Dawley rats were divided into the following groups - pelvic irradiation, cholestyramine-concurrent radiation, and control groups. The rats in the pelvic irradiation group were irradiated in the pelvic region with 2 Gy per day for five consecutive days. The total bile acid (TBA) levels in the ileum, colon, and feces were measured using automatic biochemical analyzer, and the levels of individual bile acids were evaluated by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The mRNA and protein expression of Asbt in ileum were assessed by qRT-PCR and Western blot assay. The rats in the cholestyramine-concurrent radiation group were administered with cholestyramine, a bile acid-chelating resin, and concurrent radiation for 5 days. The body weight of rats was monitored daily, and the degree of diarrhea was scored.Results: Diarrhea was observed at 2 and 3 days post-pelvic radiation. The TBA levels were significantly decreased at 4 and 5 days post-radiation in the ileum (p < .01, p < .01) and increased at 4 and 5 days post-radiation in the colon (p < .05, p < .05). The fecal excretions of TBA were significantly increased at 3, 4, and 5 days post-radiation (p < .05). The levels of individual bile acids were significantly decreased in the ileum and increased in the colon and feces, post-radiation. The mRNA and protein expression of Asbt in the ileum gradually decreased with increasing days of pelvic radiation and significantly decreased at 3 and 5 days post-radiation, respectively. Furthermore, a significant decrease in body weight was observed post-pelvic radiation, and cholestyramine administration did not reverse the weight loss. However, the incidence of RID was decreased after administration of cholestyramine.Conclusions: Bile acid malabsorption is partially responsible for RID post-pelvic radiation in rats, and the potential mechanism is related to the downregulation of the ileal Asbt.