The Protective Effects of Apigenin Against Radiation‐Induced Intestinal Injury
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ABSTRACT:
SUBMITTER: Liu D
PROVIDER: S-EPMC9289922 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Project description:Intestinal injury is a potential cause of death after high-dose radiation exposure. The aim of the present study was to investigate the protective effects of resveratrol against radiation-induced small intestine injury.C57BL/6 N mice were irradiated and treated with resveratrol and/or Ex527 (a potent Sirt1 inhibitor), and subsequent examining intestinal morphological changes, and crypt cell apoptosis. Then, the expression and enzyme activity of SOD2 in the small intestine were examined. Furthermore, Sirt1 and acetylated p53 expression was analysed.Compared to the vehicle control, treatment with resveratrol improved intestinal morphology, decreased apoptosis of crypt cells, maintained cell regeneration, and ameliorated SOD2 expression and activity. Resveratrol also regulated Sirt1 and acetylated p53 expression perturbed by irradiation in the small intestine. The protective effect of resveratrol against ionizing radiation induced small intestine injury was significantly inhibited by Ex527.Our results suggest that resveratrol decreases the effects of radiation on intestinal injury at least partly via activation of Sirt1.
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Project description:Radiation-induced intestinal injury is one of the major side effects in patients receiving radiation therapy. There is no specific treatment for radiation enteritis in the clinic. We designed and synthesized a new compound named XH-105, which is expected to cleave into polyphenol and aminothiol in vivo to mitigate radiation injury. In the following study, we describe the beneficial effects of XH-105 against radiation-induced intestinal injury. C57BL/6J mice were treated by gavage with XH-105 1 hour before total body irradiation (TBI), and the survival rate was monitored. Histological changes were examined, and survival of Lgr5+ intestinal stem cells Ki67+ cells, villi+ enterocytes and lysozymes was determined by immunohistochemistry. DNA damage and cellular apoptosis in intestinal tissue were also evaluated. Compared to vehicle-treated mice after TBI, XH-105 treatment significantly enhanced the survival rate, attenuated structural damage of the small intestine, decreased the apoptotic rate, reduced DNA damage, maintained cell regeneration and promoted crypt proliferation and differentiation. XH-105 also reduced the expression of Bax and p53 in the small intestine. These data suggest that XH-105 is beneficial for the protection of radiation-induced intestinal injury by inhibiting the p53-dependent apoptosis signalling pathway.
| S-EPMC6378229 | biostudies-literature
Project description:Intestinal injury is the primary toxicity of radiotherapy for pelvic and abdominal tumors, and it is also one of the common acute complications of radiotherapy. At present, there are no effective drugs to prevent intestinal injury in the clinic. Zingerone is a natural product with radioprotective effects. In this study, a novel compound (thiazolidine hydrochloride, TZC01) was synthesized by structural modification of zingerone. The effects of TZC01 on preventing intestinal injury from radiation were further investigated in this study. C57BL/6N mice were exposed to a lethal dose of abdominal irradiation (ABI) with and without TZC01 treatments. The morphological changes of the intestine and various makers of intestinal crypt cells were investigated. Treatment with TZC01 improved the survival rate of mice exposed to 12 Gy ABI. Moreover, TZC01 protected the intestinal morphology of mice, decreased the apoptotic rate of intestinal crypt cells, maintained cell regeneration and promoted crypt cell proliferation and differentiation. This study suggests that TZC01 has preventive and therapeutic effects on radiation enteritis by promoting the proliferation and differentiation of crypt cells to protect the small intestine from the toxic effects of ionizing radiation. Furthermore, the study of TCZ01 lays a strong foundation for developing novel radioprotectors with multiple properties.
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Project description:Radiation-induced intestinal injury (RIII) is a common complication after radiation therapy in patients with pelvic, abdominal, or retroperitoneal tumours. Recently, in the model of DSS (Dextran Sulfate Sodium Salt) -induced intestinal inflammatory injury, it has been found in the study that transgenic mice expressing hVDR in IEC (Intestinal Epithelial Cell) manifest highly anti-injury properties in colitis, suggesting that activated VDR in the epithelial cells of intestine may inhibit colitis by protecting the mucosal epithelial barrier. In this study, we investigated the effect of the expression and regulation of VDR on the protection of RIII, and the radiosensitivity in vitro experiments, and explored the initial mechanism of VDR in regulating radiosensitivity of IEC. As a result, we found that the expression of VDR in intestinal tissues and cells in mice can be induced by ionizing radiation. VDR agonists are able to prolong the average survival time of mice after radiation and reduce the radiation-induced intestinal injury. For lack of vitamin D, the radiosensitivity of intestinal epithelial cells in mice increased, which can be reduced by VDR activation. Ensuing VDR activation, the radiation-induced intestinal stem cells damage is decreased, and the regeneration and differentiation of intestinal stem cells is promoted as well. Finally, on the basis of sequencing analysis, we validated and found that VDR may target the HIF/PDK1 pathway to mitigate RIII. We concluded that agonism or upregulation of VDR expression attenuates radiation-induced intestinal damage in mice and promotes the repair of epithelial damage in intestinal stem cells.
| S-EPMC9843524 | biostudies-literature
Project description:The hematopoietic system is sensitive to radiation. In this research, new aryl sulfone derivatives (XH-201 and XH-202) containing a nitrogen heterocycle were designed and synthesized and their radio-protective efficacies with regard to the hematopoietic system were evaluated. XH-201 administration significantly increased the survival rate of mice after 8.0 Gy total body irradiation (TBI). The results showed that XH-201 treatment not only increased the white blood cells, platelets counts and the percentage of hematopoietic progenitor cells and hematopoietic stem cells in mice exposed to 4.0 Gy TBI but also decreased DNA damage, as determined by flow cytometric analysis of histone H2AX phosphorylation. In addition, our data demonstrated that XH-201 decreased the mitochondrial reactive oxygen species (ROS) levels in hematopoietic cells. Overall, these data suggest that XH-201 is beneficial for the protection of the hemoatopoietic system against radiation-induced injuries.
| S-EPMC7299261 | biostudies-literature
Project description:BackgroundRadiation-induced lung injury (RILI) is a common complication of thoracic cancer radiation therapy. Currently, there is no effective treatment for RILI. RILI is associated with chronic inflammation, this injury is perpetuated by the stimulation of chemokines and proinflammatory cytokines. Recent studies have demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a pivotal role in inflammation and fibrosis. This study aimed to investigate the protective effect of GM-CSF against the development of RILI in lung tissue.MethodFirst, a single fraction of radiation at a dose of 16 Gy was targeted at the entire thorax of wild-type (WT) C57BL/6 mice and GM-CSF-/- mice to induce RILI. Second, we detected the radioprotective effects of GM-CSF by measuring the inflammatory biomarkers and fibrosis alteration on radiated lung tissues. Furthermore, we investigated the potential mechanism of GM-CSF protective effects in RILI.ResultsThe GM-CSF-/- mice sustained more severe RILI than the WT mice. RILI was significantly alleviated by GM-CSF treatment. Intraperitoneally administered GM-CSF significantly inhibited inflammatory cytokine production and decreased epithelial-mesenchymal transition (EMT) in the RILI mouse model.ConclusionsGM-CSF was shown to be an important modulator of RILI through regulating inflammatory cytokines, which provides a new strategy for the prevention and treatment of RILI.
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Project description:Radiation-induced intestinal injury (RIII) occurs after high doses of radiation exposure. RIII restricts the therapeutic efficacy of radiotherapy in cancer and increases morbidity and mortality in nuclear disasters. Currently, there is no approved agent for the prevention or treatment of RIII. Here, we reported that the disulfiram, an FDA-approved alcohol deterrent, prolonged the survival in mice after lethal irradiation. Pretreatment with disulfiram inhibited proliferation within 24 h after irradiation, but improved crypt regeneration at 3.5 days post-irradiation. Mechanistically, disulfiram promoted Lgr5+ intestinal stem cells (ISCs) survival and maintained their ability to regenerate intestinal epithelium after radiation. Moreover, disulfiram suppresses DNA damage accumulation, thus inhibits aberrant mitosis after radiation. Unexpectedly, disulfiram treatment did not inhibit crypt cell apoptosis 4 h after radiation and the regeneration of crypts from PUMA-deficient mice after irradiation was also promoted by disulfiram. In conclusion, our findings demonstrate that disulfiram regulates the DNA damage response and survival of ISCs through affecting the cell cycle. Given its radioprotective efficacy and decades of application in humans, disulfiram is a promising candidate to prevent RIII in cancer therapy and nuclear accident.
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Project description:This experiment was conducted to evaluate whether pretreatment with fenofibrate could mitigate acute lung injury (ALI) in a mice model of intestinal ischemia/reperfusion (I/R). Male C57BL/6 mice were randomly assigned into three groups (n = 6): sham, intestinal I/R + vehicle, and intestinal I/R + fenofibrate. Intestinal I/R was achieved by clamping the superior mesenteric artery. Fenofibrate (100 mg/kg) or equal volume of vehicle was injected intraperitoneally 60 minutes before the ischemia. At the end of experiment, measurement of pathohistological score, inflammatory mediators and other markers were performed. In addition, a 24-hour survival experiment was conducted in intestinal I/R mice treated with fenofibrate or vehicle. The chief results were as anticipated. Pathohistological evaluation indicated that fenofibrate ameliorated the local intestine damage and distant lung injury. Pretreatment with fenofibrate significantly decreased inflammatory factors in both the intestine and the lung. Consistently, renal creatine levels and hepatic ALT levels were significantly decreased in the fenofibrate group. Moreover, serum systemic inflammatory response indicators were significantly alleviated in the fenofibrate group. In addition, fenofibrate administration significantly improved the survival rate. Collectively, our data indicated that pretreatment with fenofibrate prior to ischemia attenuated intestinal I/R injury and ALI.
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Project description:Ischemic retinal damage, a common condition associated with retinal vascular occlusion, glaucoma, diabetic retinopathy, and other eye diseases, threatens the vision of millions of people worldwide. It triggers excessive inflammation, oxidative stress, apoptosis, and vascular dysfunction, leading to the loss and death of retinal ganglion cells. Unfortunately, minority drugs are available for treating retinal ischemic injury diseases, and their safety are limited. Therefore, there is an urgent need to develop more effective treatments for ischemic retinal damage. Natural compounds have been reported to have antioxidant, anti-inflammatory, and antiapoptotic properties that can be used to treat ischemic retinal damage. In addition, many natural compounds have been shown to exhibit biological functions and pharmacological properties relevant to the treatment of cellular and tissue damage. This article reviews the neuroprotective mechanisms of natural compounds involve treating ischemic retinal injury. These natural compounds may serve as treatments for ischemia-induced retinal diseases.
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Project description:The reproductive system is vulnerable to ionizing radiation, which is a hot research topic at present. We tested the effect of polydatin on spermatocytes(GC-1 cells) after X-ray irradiation. The reproductive damage model of C.elegans was established by 60Coγ-ray, and the protective effect of polydatin on reproductive damage caused by ionizing radiation was evaluated. We quantified the ROS levels of GC-1 cells and C.elegans after irradiation with polydatin and evaluated the anti-apoptosis effect of polydatin at proper concentration. Differential genes of C.elegans reproductive damage were screened out from transcriptome sequencing results and comparable GEO datasets. It was proved that 100μM polydatin significantly reduced the apoptosis of GC-1 cells induced by 2 Gy X-ray. In addition, the longevity, reproductive capacity, germ cell apoptosis and spawning and hatching capacity of polydatin were tested. The results showed that 100 μM polydatin content significantly increased the influence of 50 Gy 60Coγ-ray on reproductive capacity of C.elegans. Quantitative analysis of mRNA and protein levels of apoptosis-related genes and reproductive-related genes by qRT-PCR and Western blotcon firmed that polydatin with appropriate dosage had good protective effects on reproductive damage caused by radiation, which laid a foundation for the application research of polydatin in radiation protection.
| S-EPMC9244944 | biostudies-literature