scholarly journals Low-Dose Radiation Activates Akt and Nrf2 in the Kidney of Diabetic Mice: A Potential Mechanism to Prevent Diabetic Nephropathy

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao Xing ◽  
Chi Zhang ◽  
Minglong Shao ◽  
Qingyue Tong ◽  
Guirong Zhang ◽  
...  

Repetitive exposure of diabetic mice to low-dose radiation (LDR) at 25 mGy could significantly attenuate diabetes-induced renal inflammation, oxidative damage, remodeling, and dysfunction, for which, however, the underlying mechanism remained unknown. The present study explored the effects of LDR on the expression and function of Akt and Nrf2 in the kidney of diabetic mice. C57BL/6J mice were used to induce type 1 diabetes with multiple low-dose streptozotocin. Diabetic and age-matched control mice were irradiated with whole body X-rays at either single 25 mGy and 75 mGy or accumulated 75 mGy (25 mGy daily for 3 days) and then sacrificed at 1–12 h for examining renal Akt phosphorylation and Nrf2 expression and function. We found that 75 mGy of X-rays can stimulate Akt signaling pathway and upregulate Nrf2 expression and function in diabetic kidneys; single exposure of 25 mGy did not, but three exposures to 25 mGy of X-rays could offer a similar effect as single exposure to 75 mGy on the stimulation of Akt phosphorylation and the upregulation of Nrf2 expression and transcription function. These results suggest that single 75 mGy or multiple 25 mGy of X-rays can stimulate Akt phosphorylation and upregulate Nrf2 expression and function, which may explain the prevention of LDR against the diabetic nephropathy mentioned above.

2002 ◽  
Vol 21 (2) ◽  
pp. 85-90 ◽  
Author(s):  
L E Feinendegen

This review first summarizes experimental data on biological effects of different concentrations of ROS in mammalian cells and on their potential role in modifying cell responses to toxic agents. It then attempts to link the role of steadily produced metabolic ROS at various concentrations in mammalian cells to that of environmentally derived ROS bursts from exposure to ionizing radiation. The ROS from both sources are known to both cause biological damage and change cellular signaling, depending on their concentration at a given time. At low concentrations signaling effects of ROS appear to protect cellular survival and dominate over damage, and the reverse occurs at high ROS concentrations. Background radiation generates suprabasal ROS bursts along charged particle tracks several times a year in each nanogram of tissue, i.e., average mass of a mammalian cell. For instance, a burst of about 200 ROS occurs within less than a microsecond from low-LET irradiation such as X-rays along the track of a Compton electron (about 6 keV, ranging about 1 μm). One such track per nanogram tissue gives about 1 mGy to this mass. The number of instantaneous ROS per burst along the track of a 4-meV ¬-particle in 1 ng tissue reaches some 70000. The sizes, types and sites of these bursts, and the time intervals between them directly in and around cells appear essential for understanding low-dose and low dose-rate effects on top of effects from endogenous ROS. At background and low-dose radiation exposure, a major role of ROS bursts along particle tracks focuses on ROS-induced apoptosis of damage-carrying cells, and also on prevention and removal of DNA damage from endogenous sources by way of temporarily protective, i.e., adaptive, cellular responses. A conclusion is to consider low-dose radiation exposure as a provider of physiological mechanisms for tissue homoeostasis.


Dose-Response ◽  
2018 ◽  
Vol 16 (3) ◽  
pp. 155932581878984 ◽  
Author(s):  
Jie Cheng ◽  
Fengsheng Li ◽  
Guanjun Wang ◽  
Weiying Guo ◽  
Shan Huang ◽  
...  

To explore an optimal frequency of whole-body low-dose radiation (LDR) to protect the kidney from diabetes, type 1 diabetic mice were induced with multiple injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic or age-matched normal mice received whole-body exposure to 12.5 or 25 mGy either every other day or weekly for 4 or 8 weeks. Diabetes decreased the urinary creatinine and increased the microalbumin in urine, renal accumulation of 3-nitrotyrosine and 4-hydroxynonenal, and renal expression of collagen IV and fibronectin. All these renal pathological and functional changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens. However, whole-body exposure of diabetic mice to 25 mGy weekly and to 12.5 mGy every other day for 8 weeks provided a better prevention of diabetic nephropathy than other LDR regimens. Furthermore, whole-body exposure to 25 mGy weekly for 8 weeks showed no detectable effect on the kidney of normal mice, but whole-body exposure to normal mice at 12.5 mGy every other day for 8 weeks increased urinary microalbumin and renal expression of collagen IV and fibronectin. These results suggest that whole-body exposure to LDR at 25 mGy weekly is the optimal condition of LDR to protect the kidney from diabetes.


Dose-Response ◽  
2018 ◽  
Vol 16 (2) ◽  
pp. 155932581878144 ◽  
Author(s):  
Paul A. Oakley ◽  
Deed E. Harrison

Evidence-based contemporary spinal rehabilitation often requires radiography. Use of radiography (X-rays or computed tomography scans) should not be feared, avoided, or have their exposures lessened to decrease patient dose possibly jeopardizing image quality. This is because all fears of radiation exposures from medical diagnostic imaging are based on complete fabrication of health risks based on an outdated, invalid linear model that has simply been propagated for decades. We present 7 main arguments for continued use of radiography for routine use in spinal rehabilitation: (1) the linear no-threshold model for radiation risk estimates is invalid for low-dose exposures; (2) low-dose radiation enhances health via the body’s adaptive response mechanisms (ie, radiation hormesis); (3) an X-ray with low-dose radiation only induces 1 one-millionth the amount of cellular damage as compared to breathing air for a day; (4) radiography is below inescapable natural annual background radiation levels; (5) radiophobia stems from unwarranted fears and false beliefs; (6) radiography use leads to better patient outcomes; (7) the risk to benefit ratio is always beneficial for routine radiography. Radiography is a safe imaging method for routine use in patient assessment, screening, diagnosis, and biomechanical analysis and for monitoring treatment progress in daily clinical practice.


2009 ◽  
Vol 297 (6) ◽  
pp. E1366-E1377 ◽  
Author(s):  
Chi Zhang ◽  
Yi Tan ◽  
Weiying Guo ◽  
Cai Li ◽  
Shunzi Ji ◽  
...  

Renal protection against diabetes-induced pathogenic injuries by multiple exposures to low-dose radiation (LDR) was investigated to develop a novel approach to the prevention of renal disease for diabetic subjects. C57BL/6J mice were given multiple low-dose streptozotocin (STZ; 60 × 6 mg/kg) to produce a type 1 diabetes. Two weeks after diabetes onset, some of diabetic mice and age-matched nondiabetic mice were exposed whole body to 25 mGy X-rays every other day for 2, 4, 8, 12, and 16 wk. Diabetes caused a significant renal dysfunction, shown by time-dependent increase in urinary microalbumin (Malb) and decrease in urinary creatinine (Cre), and pathological changes, shown by significant increases in renal structural changes and PAS-positive staining. However, diabetes-induced renal dysfunction and pathological changes were significantly, albeit partially, attenuated by multiple exposures to LDR. Furthermore, LDR protection against diabetes-induced renal dysfunction and pathological changes was associated with a significant suppression of diabetes-increased systemic and renal inflammation, shown by significant increases in serum and renal TNFα, ICAM-1, IL-18, MCP-1, and PAI-1 contents. To further explore the mechanism by which LDR prevents diabetes-induced renal pathological changes, renal oxidative damage was examined by Western blotting and immunohistochemical staining for 3-nitrotyrosine and 4-hydroxynonenal. Significant increase in oxidative damage was observed in diabetic mice, but not diabetic mice, with LDR. Renal fibrosis, examined by Western blotting of connective tissue growth factor and Masson's trichrome staining, was also evident in the kidneys of diabetic mice but not diabetic mice with LDR. These results suggest that multiple exposures to LDR significantly suppress diabetes-induced systemic and renal inflammatory response and renal oxidative damage, resulting in a prevention of the renal dysfunction and fibrosis.


2010 ◽  
Vol 13 (01) ◽  
pp. 1-12 ◽  
Author(s):  
Jean Dubousset ◽  
Georges Charpak ◽  
Wafa Skalli ◽  
Jacques Deguise ◽  
Gabriel Kalifa

Very precise combined work between multidisciplinary partners (radiation engineers in physics, engineers in biomechanics, medical radiologists and orthopedic pediatric surgeons) has led to the concept and development of a new low-dose radiation device named EOS. This device has three main advantages: (1) Thanks to the invention of Georges Charpak who designed gaseous detectors for X-rays, the reduction of dose necessary to obtain a good image of skeletal system was 8 to 10 times less for 2D imaging; compared to the dose necessary to obtain a 3D reconstruction from CT scan cuts, the reduction factor was 800 to 1000. (2) The accuracy of 3D reconstruction obtained is better than that of 3D reconstruction from CT scan cuts. (3) The patient in addition gets imaged in a standing functional position, thanks to the AP and lateral X-rays obtained from head to feet simultaneously. This is a big advantage compared to CT scans which are used only in lying position. From the simultaneous AP and lateral X-rays of the whole body obtained via the 3D bone external envelop technique, the biomechanics engineers obtain 3D reconstruction of every level of osteo-articular system, especially for spine, in standing position with an acceptable period of time for reconstruction. This (in spite of the evolution of standing MRI) allows more precise bone reconstruction in orthopedics, especially at the level of the entire skeleton, including the head, spine, pelvis, lower limbs, giving new consideration for physiology, physiopathology and therapeutics.


2014 ◽  
Vol 90 (3) ◽  
pp. 224-230 ◽  
Author(s):  
Chi Zhang ◽  
Xiao Xing ◽  
Fangfang Zhang ◽  
Minglong Shao ◽  
Shuzi Jin ◽  
...  

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582095954 ◽  
Author(s):  
Paul A. Oakley ◽  
Deed E. Harrison

All too often the family physician, orthopedic surgeon, dentist or chiropractor is met with radiophobic concerns about X-ray imaging in the clinical setting. These concerns, however, are unwarranted fears based on common but ill-informed and perpetuated ideology versus current understanding of the effects of low-dose radiation exposures. Themes of X-ray hesitancy come in 3 forms: 1. All radiation exposures are harmful (i.e. carcinogenic); 2. Radiation exposures are cumulative; 3. Children are more susceptible to radiation. Herein we address these concerns and find that low-dose radiation activates the body’s adaptive responses and leads to reduced cancers. Low-dose radiation is not cumulative as long as enough time (e.g. 24 hrs) passes prior to a repeated exposure, and any damage is repaired, removed, or eliminated. Children have more active immune systems; the literature shows children are no more affected than adults by radiation exposures. Medical X-rays present a small, insignificant addition to background radiation exposure that is not likely to cause harm. Doctors and patients alike should be better informed of the lack of risks from diagnostic radiation and the decision to image should rely on the best evidence, unique needs of the patient, and the expertise of the physician—not radiophobia.


2006 ◽  
Vol 79 (940) ◽  
pp. 285-294 ◽  
Author(s):  
B F Wall ◽  
G M Kendall ◽  
A A Edwards ◽  
S Bouffler ◽  
C R Muirhead ◽  
...  

2017 ◽  
Vol 58 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Norie Kanzaki ◽  
Takahiro Kataoka ◽  
Reo Etani ◽  
Kaori Sasaoka ◽  
Akihiro Kanagawa ◽  
...  

Abstract In our previous studies, we found that low-dose radiation inhibits oxidative stress–induced diseases due to increased antioxidants. Although these effects of low-dose radiation were demonstrated, further research was needed to clarify the effects. However, the analysis of oxidative stress is challenging, especially that of low levels of oxidative stress, because antioxidative substances are intricately involved. Thus, we proposed an approach for analysing oxidative liver damage via use of a self-organizing map (SOM)—a novel and comprehensive technique for evaluating hepatic and antioxidative function. Mice were treated with radon inhalation, irradiated with X-rays, or subjected to intraperitoneal injection of alcohol. We evaluated the oxidative damage levels in the liver from the SOM results for hepatic function and antioxidative substances. The results showed that the effects of low-dose irradiation (radon inhalation at a concentration of up to 2000 Bq/m3, or X-irradiation at a dose of up to 2.0 Gy) were comparable with the effect of alcohol administration at 0.5 g/kg bodyweight. Analysis using the SOM to discriminate small changes was made possible by its ability to ‘learn’ to adapt to unexpected changes. Moreover, when using a spherical SOM, the method comprehensively examined liver damage by radon, X-ray, and alcohol. We found that the types of liver damage caused by radon, X-rays, and alcohol have different characteristics. Therefore, our approaches would be useful as a method for evaluating oxidative liver damage caused by radon, X-rays and alcohol.


2019 ◽  
Vol 186 (2-3) ◽  
pp. 163-167 ◽  
Author(s):  
Lenka Jánošíková ◽  
Martina Juričeková ◽  
Martina Horváthová ◽  
Denisa Nikodemová ◽  
Andrej Klepanec ◽  
...  

Abstract One of the most common usages of radiation in current medical diagnosis is computed tomography (CT) using X-rays. The potential health risk of CT scans has been discussed in various studies to determine whether low-dose radiation from CT could enhance the chromosome aberration yields in pediatric patients and increase their risk of carcinogenesis. For this reason, it is of great interest to study the effects of low-dose radiation. The induction of DNA damage by a CT scan examination has been demonstrated in several reports by the γ-H2AX assay, the micronuclei assay and dicentrics measurements. However, the results of most studies showed limitations. On the other hand, epidemiological studies give contradictory results for post-natal radiation exposure in the low-dose range, so it is still difficult to draw conclusions about the effects of CT examinations and risk of carcinogenesis. This article provides an overview of previously published data and summarizes the current state of knowledge.


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