ABSTRACT
Intestinal injury is one of the major side effects that are induced by medical radiation exposure, and has limited effective therapies. In this study, we investigated the beneficial effects of sanguinarine (SAN) on intestinal injury induced by ionizing radiation (IR) both in vitro and in vivo. Mice were exposed to whole abdominal irradiation (WAI) to mimic clinical scenarios. SAN was injected intraperitoneally to mitigate IR-induced injury. Histological examination was performed to assess the tissue injuries of the spleen and small intestine. A small intestinal epithelial cell line-6 (IEC-6) was analyzed for its viability and apoptosis in vitro under different treatments. Inflammation-related pathways and serum inflammatory cytokines were detected via Western blot analysis and ELISA, respectively. High-throughput sequencing was used to characterize the gut microbiota profile. High-performance liquid chromatography was performed to assess short-chain fatty acid contents in the colon. In vitro, SAN pretreatment protected cell viability and reduced apoptosis in IEC-6 cells. In vivo, SAN pretreatment protected immune organs, alleviated intestinal injury, and promoted intestinal recovery. SAN also reduced the levels of inflammatory cytokines, suppressed high mobility group box 1 (HMGB1)/ Toll-like receptor 4 (TLR4) pathway activation, and modulated gut microbiota composition. Our findings demonstrate that the beneficial properties of SAN alleviated intestinal radiation injury. Thus, SAN represents a therapeutic option for protecting against IR-induced intestinal injury in preclinical settings.
Subject(s)
Benzophenanthridines/pharmacology , Intestine, Small/drug effects , Isoquinolines/pharmacology , Radiation Injuries, Experimental/prevention & control , Spleen/drug effects , Animals , Apoptosis/drug effects , Cell Line , Cell Survival/drug effects , Cytokines/drug effects , Dose-Response Relationship, Drug , Down-Regulation , Fatty Acids, Volatile , Gastrointestinal Microbiome/drug effects , HMGB1 Protein/drug effects , Inflammation Mediators/metabolism , Injections, Intraperitoneal , Intestine, Small/pathology , Intestine, Small/radiation effects , Male , Mice , Mice, Inbred C57BL , Radiation Injuries, Experimental/pathology , Radiation, Ionizing , Signal Transduction/drug effects , Spleen/pathology , Spleen/radiation effects , Toll-Like Receptor 4/drug effectsABSTRACT
PURPOSE: The main objective is to investigate the protective effect of camel milk (CM) on radiation-induced intestinal injury. METHODS: The C57BL/6 J mice in 2 experiments were assigned into control group (Con), irradiation group (IR), and CM+irradiation group (CM+IR). After receiving the CM via gavage for 14 days, the mice in the first experiment were exposed to 6 Gy X-ray whole body irradiation, and survival rate was compared among the groups. Mice in the second experiment were exposed to 4 Gy irradiation and sacrificed at day 7. The small intestines were collected to examine the histopathological changes and to determine the anti-oxidative index and HMGB1/TLR4 inflammatory pathway. Fasting blood was used to measure serum pro-inflammatory factors. RESULTS: Compared with the IR group, the survival time was prolonged, and survival rate was increased in the CM+IR group. CM increased levels of SOD and GSH and decreased MDA in the jejunum. Furthermore, intestinal protein expression of HMGB1/TLR4 pathway (TLR4, NF-κB, and HMGB1) was up-regulated by CM intervention. CM decreased the serum levels of TNF-α and IL-1ß and increased IL-10 level. CONCLUSIONS: CM extended the survival time and had a protective effect against radiation-induced jejunum injury by regulation of antioxidant capacity and HMGB1/TLR4/NF-κB/MyD88 inflammatory signaling pathway.
ABSTRACT
OBJECTIVE: To assess the value of bone scan imaging in determining painful vertebrae of osteoporotic vertebral compression fractures (OVCFs) patients with contraindications to MRI. METHODS: Twenty-three OVCFs patients with contraindications to MRI, diagnosed and treated in our hospital between December 2007 and November 2010, were enrolled in this retrospective study. There were 18 females and five males, aged from 57 to 87 years, with a mean age of 69.5 years. All patients underwent X-ray, CT scans examinations and bone scan to determine painful vertebrae. After the painful vertebra was defined, percutaneous kyphoplasty (PKP) was performed. Efficacy of PKP was assessed with visual analog (VAS) pain scale and the Oswestry Disability Index (ODI) preoperatively, postoperatively and during final follow-up assessments. RESULTS: The painful vertebrae shown on radiological films did not accord with those found based on bone scan imaging, with a high rate of incongruent findings (27.3%, 9/33). Radiological films showed 33 vertebrae with fractures, but only 26 vertebrae (22 patients) were selected as painful vertebrae for PKP based on bone scan imaging. There were statistically significant differences in mean VAS and ODI between the preoperative and the postoperative assessments; no significant differences were observed between postoperative and final follow-up assessments. CONCLUSIONS: For the OVCFs patients with contraindications to MRI, bone scan imaging could be used to determine painful vertebrae, which is an effective method.
