Effects of low-dose oxygen ions and protons on cardiac function and structure in male C57BL/6J mice

Seawright, John W.; Sridharan, Vijayalakshmi; Landes, Reid D.; Cao, Ming; Singh, Preeti; Koturbash, Igor; Mao, Xiaole; Miousse, Isabelle R.; Singh, Sharda P.; Nelson, Gregory A.; Hauer‐Jensen, Martin; Boerma, Marjan

doi:10.1016/j.lssr.2019.01.003

Cited by 21 publications

(30 citation statements)

References 39 publications

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“…ANOVA analyses helped to delineate several dysregulated metabolites of which seven were verified using tandem mass spectrometry as significantly altered due to γ-irradiation. These included glycerophosphocholine, phosphatidic acid, N-oleoyl histidine and amino acid methionine, which were in accordance with previously published reports [21,[23][24][25]. Moreover, among the radiation types studied here, the alteration in methionine levels was observed only in the γ-irradiation exposure group.…”

Section: Low Let γ-Radiation Induced Changes In Plasma Of Male C57bl/supporting

confidence: 93%

Identification of Plasma Lipidome Changes Associated with Low Dose Space-Type Radiation Exposure in a Murine Model

et al. 2020

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Long-term exposures to low dose space radiation may have adverse effects on human health during missions in deep space. Conventional dosimetry, monitoring of prodromal symptoms, and peripheral lymphocyte counts are of limited value as biomarkers of organ- and tissue-specific radiation injury, particularly of injuries that appear weeks or months after radiation exposure. To assess the feasibility of using plasma metabolic and lipidomic profiles as biomarkers of injury from space radiation, we used a mouse model of exposure to low doses of oxygen ions (16O) and protons (1H). Plasma profiles were compared with those of mice exposed to γ-rays as a reference set. Our results demonstrate major changes in glycerophospholipid metabolism, amino acid metabolism, as well as fatty acid metabolism. We also observed dyslipidemia and lipid peroxidation, suggesting an inflammatory phenotype with possible long-term consequences to overall health upon exposure to low doses of high linear energy transfer (LET) radiation.

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Section: Low Let γ-Radiation Induced Changes In Plasma Of Male C57bl/supporting

confidence: 93%

Identification of Plasma Lipidome Changes Associated with Low Dose Space-Type Radiation Exposure in a Murine Model

et al. 2020

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“…To quantify collagen deposition in the heart, samples were prepared as described previously [ 85 ]. Briefly, 5 µm tissue sections were rehydrated and incubated with Sirius Red supplemented with Fast Green.…”

Section: Methodsmentioning

confidence: 99%

Late Health Effects of Partial Body Irradiation Injury in a Minipig Model Are Associated with Changes in Systemic and Cardiac IGF-1 Signaling

Hritzo¹,

Aghdam²,

Legesse³

et al. 2021

IJMS

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Clinical, epidemiological, and experimental evidence demonstrate non-cancer, cardiovascular, and endocrine effects of ionizing radiation exposure including growth hormone deficiency, obesity, metabolic syndrome, diabetes, and hyperinsulinemia. Insulin-like growth factor-1 (IGF-1) signaling perturbations are implicated in development of cardiovascular disease and metabolic syndrome. The minipig is an emerging model for studying radiation effects given its high analogy to human anatomy and physiology. Here we use a minipig model to study late health effects of radiation by exposing male Göttingen minipigs to 1.9–2.0 Gy X-rays (lower limb tibias spared). Animals were monitored for 120 days following irradiation and blood counts, body weight, heart rate, clinical chemistry parameters, and circulating biomarkers were assessed longitudinally. Collagen deposition, histolopathology, IGF-1 signaling, and mRNA sequencing were evaluated in tissues. Our findings indicate a single exposure induced histopathological changes, attenuated circulating IGF-1, and disrupted cardiac IGF-1 signaling. Electrolytes, lipid profiles, liver and kidney markers, and heart rate and rhythm were also affected. In the heart, collagen deposition was significantly increased and transforming growth factor beta-1 (TGF-beta-1) was induced following irradiation; collagen deposition and fibrosis were also observed in the kidney of irradiated animals. Our findings show Göttingen minipigs are a suitable large animal model to study long-term effects of radiation exposure and radiation-induced inhibition of IGF-1 signaling may play a role in development of late organ injuries.

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“…Mice were examined in random order, and the sonographer was blinded to experimental group. Because anesthesia is known to alter cardiac physiology [ 22 ], we developed a procedure in which mice were under anesthesia for the shortest possible time during ultrasonography [ 23 ]. Hence, the day before ultrasonography, mice were anesthetized with 2% isoflurane, and hair was removed from the thorax and abdomen with depilatory cream.…”

Section: Methodsmentioning

confidence: 99%

Sex-dependent effects of genetic upregulation of activated protein C on delayed effects of acute radiation exposure in the mouse heart, small intestine, and skin

et al. 2021

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Accidental exposure to ionizing radiation may lead to delayed effects of acute radiation exposure (DEARE) in many organ systems. Activated protein C (APC) is a known mitigator of the acute radiation syndrome. To examine the role of APC in DEARE, we used a transgenic mouse model with 2- to 3-fold increased plasma levels of APC (high in APC, APCHi). Male and female APCHi mice and wild-type littermates were exposed to 9.5 Gy γ-rays with their hind-legs (bone marrow) shielded from radiation to allow long-term survival. At 3 and 6 months after irradiation, cardiac function was measured with ultrasonography. At 3 months, radiation increased cardiac dimensions in APCHi males, while decreases were seen in wild-type females. At this early time point, APCHi mice of both sexes were more susceptible to radiation-induced changes in systolic function compared to wild-types. At 6 months, a decrease in systolic function was mainly seen in male mice of both genotypes. At 6 months, specimens of heart, small intestine and dorsal skin were collected for tissue analysis. Female APCHi mice showed the most severe radiation-induced deposition of cardiac collagens but were protected against a radiation-induced loss of microvascular density. Both male and female APCHi mice were protected against a radiation induced upregulation of toll-like receptor 4 in the heart, but this did not translate into a clear protection against immune cell infiltration. In the small intestine, the APCHi genotype had no effect on an increase in the number of myeloperoxidase positive cells (seen mostly in females) or an increase in the expression of T-cell marker CD2 (males). Lastly, both male and female APCHi mice were protected against radiation-induced epidermal thickening and increase in 3-nitrotyrosine positive keratinocytes. In conclusion, prolonged high levels of APC in a transgenic mouse model had little effects on indicators of DEARE in the heart, small intestine and skin, with some differential effects in male compared to female mice.

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Effects of low-dose oxygen ions and protons on cardiac function and structure in male C57BL/6J mice

Cited by 21 publications

References 39 publications

Identification of Plasma Lipidome Changes Associated with Low Dose Space-Type Radiation Exposure in a Murine Model

Identification of Plasma Lipidome Changes Associated with Low Dose Space-Type Radiation Exposure in a Murine Model

Late Health Effects of Partial Body Irradiation Injury in a Minipig Model Are Associated with Changes in Systemic and Cardiac IGF-1 Signaling

Sex-dependent effects of genetic upregulation of activated protein C on delayed effects of acute radiation exposure in the mouse heart, small intestine, and skin

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