TLR4 Agonist Monophosphoryl Lipid A Alleviated Radiation-Induced Intestinal Injury

Guo, Jiaming; Liu, Zhe; Zhang, Danfeng; Chen, Yuanyuan; Qin, Hongran; Liu, Tingting; Liu, Cong; Cui, Jianguo; Li, Bailong; Yang, Yue; Cai, Jianming; Fu, Guosheng

doi:10.1155/2019/2121095

Cited by 14 publications

(18 citation statements)

References 37 publications

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“…However, we adopted the HINEG system, which can present the high flux of 14.1 MeV neutrons as to generate the mouse ARS model utilized here, to conquer this obstacle. Compared with our previous studies about ionizing photons protection, similar phenomena such as survival rate decline, body weight loss, critical organ shrinking, and hematopoietic tissue cell loss were also obvious in the neutron ARS model here [ 18 , 19 ]. The detriments by neutrons were much severer than that of photons, characterized by relatively low dose causing the similar outcomes and the advanced upcoming of injury peak, all of which promoted the insight of neutron biology at this condition.…”

Section: Discussionsupporting

confidence: 67%

Polydatin Attenuates 14.1 MeV Neutron-Induced Injuries via Regulating the Apoptosis and Antioxidative Pathways and Improving the Hematopoiesis of Mice

Guo

et al. 2020

Oxidative Medicine and Cellular Longevity

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With more powerful penetrability and ionizing capability, high energetic neutron radiation (HENR) often poses greater threats than photon radiation, especially on such occasions as nuclear bomb exposure, nuclear accidents, aerospace conduction, and neutron-based radiotherapy. Therefore, there emerges an urgent unmet demand in exploring highly efficient radioprotectants against HENR. In the present study, high-throughput 14.1 MeV neutrons were generated by the high-intensity D-T fusion neutron generator (HINEG) and succeeded in establishing the acute radiation syndrome (ARS) mouse model induced by HENR. A series of preclinical studies, including morphopathological assessment, flow cytometry, peripheral complete blood, and bone marrow karyocyte counting, were applied showing much more serious detriments of HENR than the photon radiation. In specific, it was indicated that surviving fraction of polydatin- (PD-) treated mice could appreciably increase to up to 100% when they were exposed to HENR. Moreover, polydatin contributed much in alleviating the HENR-induced mouse body weight loss, spleen and testis indexes decrease, and the microstructure alterations of both the spleen and the bone marrow. Furthermore, we found that the HENR-damaged hematopoiesis was greatly prevented by PD treatment in such aspects as bone marrow hemocytogenesis, splenocytes balancing, or even the peripheral blood cellularity. The additional IHC investigations revealed that PD could exert potent hematopoiesis-promoting effects against HENR via suppressing apoptosis and promoting the antioxidative enzymes such as HO-1.

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Section: Discussionsupporting

confidence: 67%

Polydatin Attenuates 14.1 MeV Neutron-Induced Injuries via Regulating the Apoptosis and Antioxidative Pathways and Improving the Hematopoiesis of Mice

Guo

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Yang et al 17 studied the protective effect on Nrf2-deficient mice after receiving whole abdominal IR with 13 Gy γ-ray. Guo et al 5 used a model of 7 Gy whole body γ-ray to examine TLR4 agonist monophosphoryl lipid A-alleviated radiation-induced intestinal injury. In our study, the absence of crypts, a considerable loss of villi, and epithelial disruption were observed in the mouse models of radiation intestinal injury.…”

Section: Discussionmentioning

confidence: 99%

“…For example, different doses of 7, 8 or 9 Gy TBI were used in previous studies for exploring radiation-induced intestinal injury on C57BL/6 mice. 5 - 7 Moreover, doses between 12 and 20 Gy WAI were tested for mortality on C57BL/6 mice model, and the results show that animals started dying at doses of 12 Gy, 15 Gy or above 16 Gy. 8 In all, the different irradiation techniques, dose rate, and the age of the mice could induce different biological outcomes among C57BL/6 mice.…”

Section: Introductionmentioning

confidence: 99%

At What Dose Can Total Body and Whole Abdominal Irradiation Cause Lethal Intestinal Injury Among C57BL/6J Mice?

Chen

Zhang

et al. 2020

Dose-Response

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Purpose and Methods: To investigate the doses of total body (TBI) and whole abdominal irradiation (WAI) induced lethal intestinal injury, healthy C57BL/6 J mice were divided randomly into 7 groups: control group; 6, 7, and 8 Gy TBI groups; and 5, 10, and 15 Gy WAI groups. The survival length, general conditions, body weight, daily food and water intake of the mice and the histopathological changes of small intestine were observed. Results: Lethal injury among C57BL/6 J mice was caused by ≥6 Gy TBI and 15 Gy WAI. Their body weight and food intake decreased, the structure of their small intestinal villi was destroyed, and the number of surviving crypts per circumference of the jejunum decreased in ≥6 Gy TBI groups and 15 Gy WAI group. The mice in the 10 Gy WAI group significantly lost weight within 5 days but recovered slowly thereafter. They also had poor appetite and reversibly damaged intestinal mucosa. Conclusions: Nonlethal intestinal injury could be induced by 10 Gy WAI, whereas lethal intestinal injury could be triggered by ≥6 Gy TBI and >15 Gy WAI in mice. Our results provided a basis for establishing radiation-induced intestinal injury models with C57BL/6 J mice.

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“…Extensive studies focus on the prevention and treatment of radio-induced intestinal injury, but no effective therapeutic measures appear so far [ 13 ]. Till now, the only FDA-approved radio-protective drug (WR2721, Amifostine, marketed as Ethyol® by Med Immune, Gaithersburg, MD) is used clinically [ 14 ], but still not free of toxicity. Hence, it is urgent to utilize a stable and reliable animal experimental model to deeply understand radio-induced intestinal injury.…”

Section: Introductionmentioning

confidence: 99%

The effects of myeloablative or non-myeloablative total body irradiations on intestinal tract in mice

et al. 2021

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Acute radiation injury caused by high-dose radiation exposure severely impedes the application of radiotherapy in cancer management. To deeply understand the side effects of radiation on intestinal tract, an irradiation murine model was applied and evaluated. C57BL/6 mice were given 4Gy non-myeloablative irradiation, 8Gy myeloablative irradiation and non-irradiation (control), respectively. Results demonstrated that the 8Gy myeloablative irradiations significantly damaged the gut barrier along with decreasing MECA32 and ZO-1. However, a slight increase of MECA32 and ZO-1 was detected in the 4Gy non-myeloablative irradiations treatment from day 5 to day 10. Further, the irradiations affected the expression of P38 and JNK MAPK but not ERK1/2 MAPK signal pathway. Moreover, irradiation had adverse effects on hematopoietic system, altered the numbers and percentages of intestinal inflammatory cells. The IL-17/AhR had big increase in the gut of 4Gy irradiation mice at day 10 compared with other groups. Both 8Gy myeloablative and 4Gy non-myeloablative irradiation disturbed the levels of short chain fatty acids in intestine. Meanwhile, high dosage of irradiation decreased the intestinal bacterial diversity and altered the community composition. Importantly, the fatty acids generating bacteria Bacteroidaceae and Ruminococcaceae played key roles in community distribution and short chain fatty acids metabolism after irradiation. Collectively, the irradiation induced gut barrier damage with dosages dependent that led to the decreased p38 MAPK and increased JNK MAPK, unbalanced the mononuclear cells of gut, disturbed intestinal bacterial community and short chain fatty acids level.

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TLR4 Agonist Monophosphoryl Lipid A Alleviated Radiation-Induced Intestinal Injury

Cited by 14 publications

References 37 publications

Polydatin Attenuates 14.1 MeV Neutron-Induced Injuries via Regulating the Apoptosis and Antioxidative Pathways and Improving the Hematopoiesis of Mice

Polydatin Attenuates 14.1 MeV Neutron-Induced Injuries via Regulating the Apoptosis and Antioxidative Pathways and Improving the Hematopoiesis of Mice

At What Dose Can Total Body and Whole Abdominal Irradiation Cause Lethal Intestinal Injury Among C57BL/6J Mice?

The effects of myeloablative or non-myeloablative total body irradiations on intestinal tract in mice

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