Sitagliptin Mitigates Total Body Irradiation-Induced Hematopoietic Injury in Mice

Wang, Meifang; Dong, Yinping; Wu, Jing; Li, Hongyan; Zhang, Junling; Lu, Lu; Zhang, Yuanyang; Zhou, Zewei; Fan, Saijun; Li, Deguan; Meng, Aimin

doi:10.1155/2020/8308616

Cited by 3 publications

(2 citation statements)

References 54 publications

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“…Accumulated evidence suggests that Sitagliptin not only regulates blood glucose but also has pleiotropic effects of anti-inflammatory, antioxidant, and antiapoptotic. Sitagliptin has been reported to have therapeutic effects on radiation-induced hematopoietic damage [ 33 ]. In our study, we found that once-daily treatment with Sitagliptin starting 1 hour before radiotherapy could protect the mice from death and weight loss induced by WAI.…”

Section: Discussionmentioning

confidence: 99%

Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder

Huang

Wanling

et al. 2022

Oxidative Medicine and Cellular Longevity

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Radiation-induced intestinal injury is a common and critical complication of radiotherapy for pelvic or abdominal tumors, with limited therapeutic strategies and effectiveness. Sitagliptin, a dipeptidyl peptidase IV (DPP4) inhibitor, has previously been reported to alleviate total body irradiation- (TBI-) induced damage of hematopoietic system in mice, but its effect on radiation-induced intestinal injury remains unclear. In this study, we confirmed that Sitagliptin could not only protect mice from death and weight loss caused by whole abdominal irradiation (WAI) but also improve the morphological structure of intestine and the regeneration ability of enterocytes. In addition, Sitagliptin significantly inhibited the production of radiation-induced proinflammatory cytokines and reduced the number of apoptotic intestinal epithelial cells and γ-H2AX expression. In vitro, we demonstrated that Sitagliptin protected HIEC-6 cells from ionizing radiation, resulting in increased cell viability and reduced DNA damage. Mechanistically, the radiation protection of Sitagliptin might be related to the upregulation of NRF2 level and the decrease of NLRP3 inflammasome activity. Importantly, Sitagliptin significantly restored radiation-induced changes in bacterial composition. In conclusion, our results suggested that Sitagliptin could reduce WAI-induced intestinal injury in mice, which may provide novel therapeutic strategy for radiation-induced intestinal injury.

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Section: Discussionmentioning

confidence: 99%

Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder

Huang

Wanling

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Radiation‐induced suppression of haematopoiesis and immune function has been one of the most life‐threatening consequences of radiation exposure 26 . In order to assess the influence of radiation on the haematopoietic system, TBI 4 Gy as a sublethal dose was selected as the challenge of radiation exposure 27,28 . Our present data demonstrated that lymphocytes maintain an impair level after 9 days TBI 4 Gy, due to the irreversibly damaged haematopoietic stem cells no longer produce mature blood cells.…”

Section: Discussionmentioning

confidence: 64%

MST1/2 inhibitor XMU‐MP‐1 alleviates the injury induced by ionizing radiation in haematopoietic and intestinal system

Zhou

Wang

et al. 2022

J Cellular Molecular Medi

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The Hippo signalling pathway has been considered as potential therapeutic target in self‐renewal and differentiation of stem and progenitor cells. Thus, mammalian Ste20‐like kinase 1/2 (MST1/2) as the core serine‐threonine kinases in the Hippo signalling pathway has been investigated for its role in immunological disease. However, little information of MST1/2 function in bone marrow suppression induced by ionizing radiation was fully investigated. Here, we reported that MST1/2 inhibitor XMU‐MP‐1 could rescue the impaired haematopoietic stem cells (HSCs) and progenitor cells (HPCs) function under oxidative stress condition. Also, XMU‐MP‐1 pretreatment markedly alleviated the small intestinal system injury caused by the total body irradiation 9 Gy and extended the average survival days of the mice exposed to the lethal dose radiation. Therefore, irradiation exposure causes the serious pathological changes of haematopoietic and intestinal system, and XMU‐MP‐1 could prevent the ROS production, the haematopoietic cells impairment and the intestinal injury. These detrimental effects may be associated with regulating NOX/ROS/P38MARK pathway by MST1/2.

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Role of Dipeptidyl Peptidase 4 Inhibitors in Antidiabetic Treatment

Yin

Wang

et al. 2022

Molecules

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In recent years, important changes have occurred in the field of diabetes treatment. The focus of the treatment of diabetic patients has shifted from the control of blood glucose itself to the overall management of risk factors, while adjusting blood glucose goals according to individualization. In addition, regulators need to approve new antidiabetic drugs which have been tested for cardiovascular safety. Thus, the newest class of drugs has been shown to reduce major adverse cardiovascular events, including sodium-glucose transporter 2 (SGLT2) and some glucagon like peptide 1 receptor (GLP1) analog. As such, they have a prominent place in the hyperglycemia treatment algorithms. In recent years, the role of DPP4 inhibitors (DPP4i) has been modified. DPP4i have a favorable safety profile and anti-inflammatory profile, do not cause hypoglycemia or weight gain, and do not require dose escalation. In addition, it can also be applied to some types of chronic kidney disease patients and elderly patients with diabetes. Overall, DPP4i, as a class of safe oral hypoglycemic agents, have a role in the management of diabetic patients, and there is extensive experience in their use.

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Sitagliptin Mitigates Total Body Irradiation-Induced Hematopoietic Injury in Mice

Cited by 3 publications

References 54 publications

Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder

Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder

MST1/2 inhibitor XMU‐MP‐1 alleviates the injury induced by ionizing radiation in haematopoietic and intestinal system

Role of Dipeptidyl Peptidase 4 Inhibitors in Antidiabetic Treatment

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