scholarly journals Dose and Dose Rate-Dependent Effects of Low-Dose Irradiation on Inflammatory Parameters in ApoE-Deficient and Wild Type Mice

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3251
Author(s):  
Annegret Glasow ◽  
Ina Patties ◽  
Nicholas D. Priest ◽  
Ronald E. J. Mitchel ◽  
Guido Hildebrandt ◽  
...  
Keyword(s):  
Dose Rate ◽  
Plasma Levels ◽  
Low Dose ◽  
Time Dependent ◽  
Whole Body ◽  
Wild Type ◽  
Adhesion Properties ◽  
Dose Rates ◽  
Anti Inflammatory

Anti-inflammatory low-dose therapy is well established, whereas the immunomodulatory impact of doses below 0.1 Gy is much less clear. In this study, we investigated dose, dose rate and time-dependent effects in a dose range of 0.005 to 2 Gy on immune parameters after whole body irradiation (IR) using a pro-inflammatory (ApoE−/−) and a wild type mouse model. Long-term effects on spleen function (proliferation, monocyte expression) were analyzed 3 months, and short-term effects on immune plasma parameters (IL6, IL10, IL12p70, KC, MCP1, INFγ, TGFβ, fibrinogen, sICAM, sVCAM, sE-selectin/CD62) were analyzed 1, 7 and 28 days after Co60 γ-irradiation (IR) at low dose rate (LDR, 0.001 Gy/day) and at high dose rate (HDR). In vitro measurements of murine monocyte (WEHI-274.1) adhesion and cytokine release (KC, MCP1, IL6, TGFβ) after low-dose IR (150 kV X-ray unit) of murine endothelial cell (EC) lines (H5V, mlEND1, bEND3) supplement the data. RT-PCR revealed significant reduction of Ki67 and CD68 expression in the spleen of ApoE−/− mice after 0.025 to 2 Gy exposure at HDR, but only after 2 Gy at LDR. Plasma levels in wild type mice, showed non-linear time-dependent induction of proinflammatory cytokines and reduction of TGFβ at doses as low as 0.005 Gy at both dose rates, whereas sICAM and fibrinogen levels changed in a dose rate-specific manner. In ApoE−/−−/− mice, levels of sICAM increased and fibrinogen decreased at both dose rates, whereas TGFβ increased mainly at HDR. Non-irradiated plasma samples revealed significant age-related enhancement of cytokines and adhesion molecules except for sICAM. In vitro data indicate that endothelial cells may contribute to systemic IR effects and confirm changes of adhesion properties suggested by altered sICAM plasma levels. The differential immunomodulatory effects shown here provide insights in inflammatory changes occurring at doses far below standard anti-inflammatory therapy and are of particular importance after diagnostic and chronic environmental exposures.

scholarly journals Preventive effects of Salvia officinalis leaf extract on insulin resistance and inflammation in a model of high fat diet-induced obesity in mice that responds to rosiglitazone

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4166 ◽  
Author(s):  
Mohamed R. Ben Khedher ◽  
Mohamed Hammami ◽  
Jonathan R.S. Arch ◽  
David C. Hislop ◽  
Dominic Eze ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Inflammatory Cytokines ◽  
Plasma Levels ◽  
Low Dose ◽  
Tolerance Test ◽  
Salvia Officinalis ◽  
Anti Inflammatory

Background Salvia officinalis (sage) is a native plant to the Mediterranean region and has been used for a long time in traditional medicine for various diseases. We investigated possible anti-diabetic, anti-inflammatory and anti-obesity effects of sage methanol (MetOH) extract in a nutritional mouse model of obesity, inflammation and insulin resistance, as well as its effects on lipolysis and lipogenesis in 3T3-L1 cells. Methods Diet-induced obese (DIO) mice were treated for five weeks with sage methanol extract (100 and 400 mg kg−1/day bid), or rosiglitazone (3 mg kg−1/day bid), as a positive control. Energy expenditure, food intake, body weight, fat mass, liver glycogen and lipid content were evaluated. Blood glucose, and plasma levels of insulin, lipids leptin and pro- and anti-inflammatory cytokines were measured throughout the experiment. The effects of sage MetOH extract on lipolysis and lipogenesis were tested in vitro in 3T3-L1 cells. Results After two weeks of treatment, the lower dose of sage MetOH extract decreased blood glucose and plasma insulin levels during an oral glucose tolerance test (OGTT). An insulin tolerance test (ITT), performed at day 29 confirmed that sage improved insulin sensitivity. Groups treated with low dose sage and rosiglitazone showed very similar effects on OGTT and ITT. Sage also improved HOMA-IR, triglycerides and NEFA. Treatment with the low dose increased the plasma levels of the anti-inflammatory cytokines IL-2, IL-4 and IL-10 and reduced the plasma level of the pro-inflammatory cytokines IL-12, TNF-α, and KC/GRO. The GC analysis revealed the presence of two PPARs agonist in sage MetOH extract. In vitro, the extract reduced in a dose-related manner the accumulation of lipid droplets; however no effect on lipolysis was observed. Conclusions Sage MetOH extract at low dose exhibits similar effects to rosiglitazone. It improves insulin sensitivity, inhibits lipogenesis in adipocytes and reduces inflammation as judged by plasma cytokines. Sage presents an alternative to pharmaceuticals for the treatment of diabetes and associated inflammation.

Dose-Rate Effects of Protons and Light Ions for DNA Damage Induction, Survival and Transformation in Apparently Normal Primary Human Fibroblasts

2021 ◽  
Author(s):  
Paula V. Bennett ◽  
Alicia M. Johnson ◽  
Sarah E. Ackerman ◽  
Pankaj Chaudhary ◽  
Deborah J. Keszenman ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Survival ◽  
Dose Rate ◽  
Low Dose ◽  
Human Fibroblasts ◽  
Dose Rates ◽  
In Vitro Transformation ◽  
Dose Rate Effects ◽  
Rate Effects

We report on effects of low-dose exposures of accelerated protons delivered at high-dose rate (HDR) or a simulated solar-particle event (SPE) like low-dose rate (LDR) on immediate DNA damage induction and processing, survival and in vitro transformation of low passage NFF28 apparently normal primary human fibroblasts. Cultures were exposed to 50, 100 and 1,000 MeV monoenergetic protons in the Bragg entrance/plateau region and cesium-137 γ rays at 20 Gy/h (HDR) or 1 Gy/h (LDR). DNA double-strand breaks (DSB) and clustered DNA damages (containing oxypurines and abasic sites) were measured using transverse alternating gel electrophoresis (TAFE) and immunocytochemical detection/scoring of colocalized γ-H2AX pS139/53BP1 foci, with their induction being linear energy transfer (LET) dependent and dose-rate sparing observed for the different damage classes. Relative biological effectiveness (RBE) values for cell survival after proton irradiation at both dose-rates ranged from 0.61–0.73. Transformation RBE values were dose-rate dependent, ranging from ∼1.8–3.1 and ∼0.6–1.0 at low doses (≤30 cGy) for HDR and LDR irradiations, respectively. However peak transformation frequencies were significantly higher (1.3–7.3-fold) for higher doses of 0.5–1 Gy delivered at SPE-like LDR. Cell survival and transformation frequencies measured after low-dose 500 MeV/n He-4, 290 MeV/n C-12 and 600 MeV/n Si-28 ion irradiations also showed an inverse dose-rate effect for transformation at SPE-like LDR. This work demonstrates the existence of inverse dose-rate effects for proton and light-ion-induced postirradiation cell survival and in vitro transformation for space mission-relevant doses and dose rates.

scholarly journals VADER: a variable dose-rate external 137Cs irradiator for internal emitter and low dose rate studies

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Guy Garty ◽  
Yanping Xu ◽  
Gary W. Johnson ◽  
Lubomir B. Smilenov ◽  
Simon K. Joseph ◽  
...  
Keyword(s):  
Dose Rate ◽  
Low Dose ◽  
Computer Control ◽  
Whole Body ◽  
External Irradiation ◽  
Dose Rates ◽  
Low Dose Rate ◽  
The Individual ◽  
Variable Dose

AbstractIn the long term, 137Cs is probably the most biologically important agent released in many accidental (or malicious) radiation disasters. It can enter the food chain, and be consumed, or, if present in the environment (e.g. from fallout), can provide external irradiation over prolonged times. In either case, due to the high penetration of the energetic γ rays emitted by 137Cs, the individual will be exposed to a low dose rate, uniform, whole body, irradiation. The VADER (VAriable Dose-rate External 137Cs irradiatoR) allows modeling these exposures, bypassing many of the problems inherent in internal emitter studies. Making use of discarded 137Cs brachytherapy seeds, the VADER can provide varying low dose rate irradiations at dose rates of 0.1 to 1.2 Gy/day. The VADER includes a mouse “hotel”, designed to allow long term simultaneous residency of up to 15 mice. Two source platters containing ~ 250 mCi each of 137Cs brachytherapy seeds are mounted above and below the “hotel” and can be moved under computer control to provide constant low dose rate or a varying dose rate mimicking 137Cs biokinetics in mouse or man. We present the VADER design and characterization of its performance over 18 months of use.

scholarly journals Preventive effects of salvia officinalis leaf extract on insulin resistance and inflammation, in high fat diet-induced-obesity mice model

2017 ◽  
Author(s):  
Mohamed Raafet Ben Khedher ◽  
Mohamed Hammami ◽  
Jonathan Robert Arch ◽  
David Christopher Hislop ◽  
Dominic Anthony Eze ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Inflammatory Cytokines ◽  
Plasma Levels ◽  
Low Dose ◽  
Tolerance Test ◽  
Native Plant ◽  
Anti Inflammatory

Background: Salvia officinalis (sage) is a native plant to the Mediterranean region and has been used for a long time in traditional medicine for various diseases. We investigated possible anti-diabetic, anti-inflammatory and anti-obesity effects of sage methanol (MetOH) extract in a nutritional mouse model of obesity, inflammation and insulin resistance, as well as its effects on lipolysis and lipogenesis in 3T3-L1 cells. Methods: Diet-induced obese (DIO) mice were treated for 5 weeks with sage methanol extract (100 and 400 mg.kg -1 /day. bid), or rosiglitazone (3 mg.kg -1 /day. bid), as a positive control. Energy expenditure, food intake, body weight, fat mass, liver glycogen and lipid content were evaluated. Blood glucose, and plasma levels of insulin, lipids leptin and pro- and anti-inflammatory cytokines were measured throughout the experiment. The effects of sage MetOH extract on lipolysis and lipogenesis were tested in vitro in 3T3-L1 cells. Results: After two weeks of treatment, the lower dose of sage MetOH extract decreased blood glucose and plasma insulin levels during an oral glucose tolerance test (OGTT). An insulin tolerance test (ITT), performed at day 29 confirmed that sage improved insulin sensitivity. Groups treated with low dose sage and rosiglitazone showed very similar effects on OGTT and ITT. Sage also improved HOMA-IR, triglycerides and NEFA. Treatment with the low dose increased the plasma levels of the anti-inflammatory cytokines IL-2, IL-4 and IL-10 and reduced the plasma level of the pro-inflammatory cytokines IL-12, TNF-α, and KC/GRO. The GC analysis revealed the presence of two PPARs agonist in sage MetOH extract. In vitro, the extract reduced in a dose-related manner the accumulation of lipid droplets; however no effect on lipolysis was observed. Conclusions: Sage MetOH extract at low dose exhibits similar effects to rosiglitazone. It improves insulin sensitivity, inhibits lipogenesis in adipocytes and reduces inflammation as judged by plasma cytokines. Sage presents an alternative to pharmaceuticals for the treatment of diabetes and associated inflammation.

scholarly journals Preventive effects of salvia officinalis leaf extract on insulin resistance and inflammation, in high fat diet-induced-obesity mice model

2017 ◽  
Author(s):  
Mohamed Raafet Ben Khedher ◽  
Mohamed Hammami ◽  
Jonathan Robert Arch ◽  
David Christopher Hislop ◽  
Dominic Anthony Eze ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Inflammatory Cytokines ◽  
Plasma Levels ◽  
Low Dose ◽  
Tolerance Test ◽  
Native Plant ◽  
Anti Inflammatory

Background: Salvia officinalis (sage) is a native plant to the Mediterranean region and has been used for a long time in traditional medicine for various diseases. We investigated possible anti-diabetic, anti-inflammatory and anti-obesity effects of sage methanol (MetOH) extract in a nutritional mouse model of obesity, inflammation and insulin resistance, as well as its effects on lipolysis and lipogenesis in 3T3-L1 cells. Methods: Diet-induced obese (DIO) mice were treated for 5 weeks with sage methanol extract (100 and 400 mg.kg -1 /day. bid), or rosiglitazone (3 mg.kg -1 /day. bid), as a positive control. Energy expenditure, food intake, body weight, fat mass, liver glycogen and lipid content were evaluated. Blood glucose, and plasma levels of insulin, lipids leptin and pro- and anti-inflammatory cytokines were measured throughout the experiment. The effects of sage MetOH extract on lipolysis and lipogenesis were tested in vitro in 3T3-L1 cells. Results: After two weeks of treatment, the lower dose of sage MetOH extract decreased blood glucose and plasma insulin levels during an oral glucose tolerance test (OGTT). An insulin tolerance test (ITT), performed at day 29 confirmed that sage improved insulin sensitivity. Groups treated with low dose sage and rosiglitazone showed very similar effects on OGTT and ITT. Sage also improved HOMA-IR, triglycerides and NEFA. Treatment with the low dose increased the plasma levels of the anti-inflammatory cytokines IL-2, IL-4 and IL-10 and reduced the plasma level of the pro-inflammatory cytokines IL-12, TNF-α, and KC/GRO. The GC analysis revealed the presence of two PPARs agonist in sage MetOH extract. In vitro, the extract reduced in a dose-related manner the accumulation of lipid droplets; however no effect on lipolysis was observed. Conclusions: Sage MetOH extract at low dose exhibits similar effects to rosiglitazone. It improves insulin sensitivity, inhibits lipogenesis in adipocytes and reduces inflammation as judged by plasma cytokines. Sage presents an alternative to pharmaceuticals for the treatment of diabetes and associated inflammation.

scholarly journals Enhancement of viability of radiosensitive (PBMC) and resistant (MDA-MB-231) clones in low-dose-rate cobalt-60 radiation therapy

2015 ◽  
Vol 48 (3) ◽  
pp. 158-165 ◽  
Author(s):  
Patrícia Lima Falcão ◽  
Bárbara Miranda Motta ◽  
Fernanda Castro de Lima ◽  
Celso Vieira Lima ◽  
Tarcísio Passos Ribeiro Campos
Keyword(s):  
Dose Rate ◽  
Low Dose ◽  
Mononuclear Cells ◽  
Standard Dose ◽  
Breast Adenocarcinoma ◽  
Peripheral Blood Mononuclear ◽  
Dose Rates ◽  
Low Dose Rate ◽  
Viability Assay

Abstract Objective: In the present study, the authors investigated the in vitro behavior of radio-resistant breast adenocarcinoma (MDA-MB-231) cells line and radiosensitive peripheral blood mononuclear cells (PBMC), as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy. Materials and Methods: The cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min–1 and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed. Results: Radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB- 231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48–72 hours post-radiation. Conclusion: Low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer.

Activated human N-ras oncogene enhances x-irradiation repair of mammalian cells in vitro less effectively at low dose rate

1985 ◽  
Vol 8 (6) ◽  
pp. 517-522 ◽  
Author(s):  
T. J. FitzGerald ◽  
C. Daugherty ◽  
K. Kase ◽  
L. A. Rothstein ◽  
M. McKenna ◽  
...  
Keyword(s):  
Dose Rate ◽  
Mammalian Cells ◽  
Low Dose ◽  
Ras Oncogene ◽  
Low Dose Rate ◽  
X Irradiation

scholarly journals Serum Metabolomic Alterations Associated with Cesium-137 Internal Emitter Delivered in Various Dose Rates

Metabolites ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 270
Author(s):  
Heng-Hong Li ◽  
Yun-Tien Lin ◽  
Evagelia C. Laiakis ◽  
Maryam Goudarzi ◽  
Waylon Weber ◽  
...  
Keyword(s):  
Dose Rate ◽  
Cumulative Dose ◽  
Low Dose ◽  
Biological Effects ◽  
Serum Samples ◽  
Dose Rates ◽  
Sphingosine 1 Phosphate ◽  
Cesium 137 ◽  
Dose Rate Effect ◽  
Medium Dose

Our laboratory and others have use radiation metabolomics to assess responses in order to develop biomarkers reflecting exposure and level of injury. To expand the types of exposure and compare to previously published results, metabolomic analysis has been carried out using serum samples from mice exposed to 137Cs internal emitters. Animals were injected intraperitoneally with 137CsCl solutions of varying radioactivity, and the absorbed doses were calculated. To determine the dose rate effect, serum samples were collected at 2, 3, 5, 7, and 14 days after injection. Based on the time for each group receiving the cumulative dose of 4 Gy, the dose rate for each group was determined. The dose rates analyzed were 0.16 Gy/day (low), 0.69 Gy/day (medium), and 1.25 Gy/day (high). The results indicated that at a cumulative dose of 4 Gy, the low dose rate group had the least number of statistically significantly differential spectral features. Some identified metabolites showed common changes for different dose rates. For example, significantly altered levels of oleamide and sphingosine 1-phosphate were seen in all three groups. On the other hand, the intensity of three amino acids, Isoleucine, Phenylalanine and Arginine, significantly decreased only in the medium dose rate group. These findings have the potential to be used in assessing the exposure and the biological effects of internal emitters.

scholarly journals Regulation of breathing pattern by IL-10

2019 ◽  
Vol 317 (1) ◽  
pp. R190-R202 ◽  
Author(s):  
Charoula Eleni Giannakopoulou ◽  
Adamantia Sotiriou ◽  
Maria Dettoraki ◽  
Michael Yang ◽  
Fotis Perlikos ◽  
...  
Keyword(s):  
Tidal Volume ◽  
Minute Ventilation ◽  
Control Of Breathing ◽  
Neonatal Rat ◽  
Whole Body ◽  
Wild Type ◽  
Rapid Shallow Breathing Index ◽  
Regulation Of Breathing ◽  
Shallow Breathing

Proinflammatory cytokines like interleukin-1β (IL-1β) affect the control of breathing. Our aim is to determine the effect of the anti-inflammatory cytokine IL-10 οn the control of breathing. IL-10 knockout mice (IL-10−/−, n = 10) and wild-type mice (IL-10+/+, n = 10) were exposed to the following test gases: hyperoxic hypercapnia 7% CO2-93% O2, normoxic hypercapnia 7% CO2-21% O2, hypoxic hypercapnia 7% CO2-10% O2, and hypoxic normocapnia 3% CO2-10% O2. The ventilatory function was assessed using whole body plethysmography. Recombinant mouse IL-10 (rIL-10; 10 μg/kg) was administered intraperitoneally to wild-type mice ( n = 10) 30 min before the onset of gas challenge. IL-10 was administered in neonatal medullary slices (10–30 ng/ml, n = 8). We found that IL-10−/−mice exhibited consistently increased frequency and reduced tidal volume compared with IL-10+/+mice during room air breathing and in all test gases (by 23.62 to 33.2%, P < 0.05 and −36.23 to −41.69%, P < 0.05, respectively). In all inspired gases, the minute ventilation of IL-10−/−mice was lower than IL-10+/+(by −15.67 to −22.74%, P < 0.05). The rapid shallow breathing index was higher in IL-10−/−mice compared with IL-10+/+mice in all inspired gases (by 50.25 to 57.5%, P < 0.05). The intraperitoneal injection of rIL-10 caused reduction of the respiratory rate and augmentation of the tidal volume in room air and also in all inspired gases (by −12.22 to −29.53 and 32.18 to 45.11%, P < 0.05, respectively). IL-10 administration in neonatal rat ( n = 8) in vitro rhythmically active medullary slice preparations did not affect either rhythmicity or peak amplitude of hypoglossal nerve discharge. In conclusion, IL-10 may induce a slower and deeper pattern of breathing.

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