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The extent of irradiation-induced long-term visceral organ damage depends on cranial/brain exposure.

Boittin FX, Denis J, Mayol JF, Martigne P, Raffin F, Coulon D, Grenier N, Drouet M, Hérodin F - PLoS ONE (2015)

Bottom Line: To investigate the influence of cranial/brain irradiation on late visceral organ damage in case of high-dose exposure, Wistar rats were irradiated at 12 Gy, with either the head and fore limbs or the two hind limbs protected behind a lead wall (head- and hind limbs-protected respectively), which allows long-term survival thanks to bone marrow protection.Histological analysis performed at this time revealed that late damages to liver, kidney and ileum were attenuated in rats with head exposed when compared to animals whose head was protected.Altogether our results demonstrate the influence of cranial/brain exposure in the onset of organ damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiobiology, IRBA (Institut de Recherche Biomédicale des Armées), Brétigny-sur-Orge, France.

ABSTRACT
In case of high-dose radiation exposure, mechanisms controlling late visceral organ damage are still not completely understood and may involve the central nervous system. To investigate the influence of cranial/brain irradiation on late visceral organ damage in case of high-dose exposure, Wistar rats were irradiated at 12 Gy, with either the head and fore limbs or the two hind limbs protected behind a lead wall (head- and hind limbs-protected respectively), which allows long-term survival thanks to bone marrow protection. Although hind limbs- and head-protected irradiated rats exhibited similar hematopoietic and spleen reconstitution, a late body weight loss was observed in hind limbs-protected rats only. Histological analysis performed at this time revealed that late damages to liver, kidney and ileum were attenuated in rats with head exposed when compared to animals whose head was protected. Plasma measurements of inflammation biomarkers (haptoglobin and the chemokine CXCL1) suggest that the attenuated organ damage in hind limbs-protected rats may be in part related to reduced acute and chronic inflammation. Altogether our results demonstrate the influence of cranial/brain exposure in the onset of organ damage.

No MeSH data available.


Related in: MedlinePlus

Kinetic analysis of plasma CXCL1 levels in 12 Gy-irradiated rats with hind limbs or head protection.A: Plasma CXCL1 levels were measured by ELISA. For each day post-irradiation (1, 4, 10, 21, 31, 37, 50, 59, 64, 71), data represent average values obtained from the plasma of 3–5 hind limbs-protected rats, 3–5 head-protected rats and 3–5 age-matched control rats from the same batch. Data from Day 64 correspond to the animals used for histology analysis. All animals were treated with Enrofloxacin. B: Average values of CXCL1 plasma levels obtained by pooling data from several days after irradiation for controls and irradiated rats with hind limbs or head protection (left panel: from 21 to 71 days post-irradiation; right panel: from 50 to 64 days post-irradiation). The number of rats used is indicated on bar charts. (** (p<0.01); * (p<0.05); n.s.: not significant).
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pone.0122900.g006: Kinetic analysis of plasma CXCL1 levels in 12 Gy-irradiated rats with hind limbs or head protection.A: Plasma CXCL1 levels were measured by ELISA. For each day post-irradiation (1, 4, 10, 21, 31, 37, 50, 59, 64, 71), data represent average values obtained from the plasma of 3–5 hind limbs-protected rats, 3–5 head-protected rats and 3–5 age-matched control rats from the same batch. Data from Day 64 correspond to the animals used for histology analysis. All animals were treated with Enrofloxacin. B: Average values of CXCL1 plasma levels obtained by pooling data from several days after irradiation for controls and irradiated rats with hind limbs or head protection (left panel: from 21 to 71 days post-irradiation; right panel: from 50 to 64 days post-irradiation). The number of rats used is indicated on bar charts. (** (p<0.01); * (p<0.05); n.s.: not significant).

Mentions: Plasma levels of Cytokine-Induced Neutrophil Chemoattractant-1 (CINC1/CXCL1) and pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) were measured by ELISA. Plasma levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) were not found to be different in irradiated animals when compared to controls between 1 and 101 days post-irradiation in our rat models (data not shown). Very transient increases in pro-inflammatory cytokines have been described a few hours following irradiation [3,5,18]. Therefore, plasma increases in pro-inflammatory cytokines may have occurred before our first measurement (24 hours post-irradiation). In contrast, we found significant plasma increases in Cytokine-Induced Neutrophil Chemoattractant-1 (CINC1/CXCL1) during both the acute and late phase after irradiation in our irradiated rat models (Fig. 6). CXCL1 belongs to the chemokine family. It is a major neutrophil chemoattractant and represents a reliable marker of inflammation [30,31]. Data from Fig. 6A indicates that CXCL1 plasma levels were strongly increased in both groups of irradiated rats 4 days post-irradiation, with the highest individual values found in rats with head protection. These results are in accordance with recent reports showing early increase in CXCL1 after irradiation [3,32]. However, increases in CXCL1 were also observed in the plasma of hind limbs- and head-protected irradiated rats in the late phase of irradiation. Data from Fig. 6B represents average values of CXCL1 plasma levels in control and irradiated animals between 21 and 71 days after irradiation (left panel) and at the very late phase after irradiation (between 50 and 64 days after irradiation, right panel). Results from Fig. 6B (left panel) indicate that CXCL1 plasma levels were significantly increased in both hind limbs- and head-protected rats between 21 and 71 days post-irradiation. In contrast, CXCL1 plasma levels were only found to be increased in head-protected rats at the very late phase of irradiation (between 50 and 64 days post-irradiation, Fig. 6B, right panel).


The extent of irradiation-induced long-term visceral organ damage depends on cranial/brain exposure.

Boittin FX, Denis J, Mayol JF, Martigne P, Raffin F, Coulon D, Grenier N, Drouet M, Hérodin F - PLoS ONE (2015)

Kinetic analysis of plasma CXCL1 levels in 12 Gy-irradiated rats with hind limbs or head protection.A: Plasma CXCL1 levels were measured by ELISA. For each day post-irradiation (1, 4, 10, 21, 31, 37, 50, 59, 64, 71), data represent average values obtained from the plasma of 3–5 hind limbs-protected rats, 3–5 head-protected rats and 3–5 age-matched control rats from the same batch. Data from Day 64 correspond to the animals used for histology analysis. All animals were treated with Enrofloxacin. B: Average values of CXCL1 plasma levels obtained by pooling data from several days after irradiation for controls and irradiated rats with hind limbs or head protection (left panel: from 21 to 71 days post-irradiation; right panel: from 50 to 64 days post-irradiation). The number of rats used is indicated on bar charts. (** (p<0.01); * (p<0.05); n.s.: not significant).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4383625&req=5

pone.0122900.g006: Kinetic analysis of plasma CXCL1 levels in 12 Gy-irradiated rats with hind limbs or head protection.A: Plasma CXCL1 levels were measured by ELISA. For each day post-irradiation (1, 4, 10, 21, 31, 37, 50, 59, 64, 71), data represent average values obtained from the plasma of 3–5 hind limbs-protected rats, 3–5 head-protected rats and 3–5 age-matched control rats from the same batch. Data from Day 64 correspond to the animals used for histology analysis. All animals were treated with Enrofloxacin. B: Average values of CXCL1 plasma levels obtained by pooling data from several days after irradiation for controls and irradiated rats with hind limbs or head protection (left panel: from 21 to 71 days post-irradiation; right panel: from 50 to 64 days post-irradiation). The number of rats used is indicated on bar charts. (** (p<0.01); * (p<0.05); n.s.: not significant).
Mentions: Plasma levels of Cytokine-Induced Neutrophil Chemoattractant-1 (CINC1/CXCL1) and pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) were measured by ELISA. Plasma levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) were not found to be different in irradiated animals when compared to controls between 1 and 101 days post-irradiation in our rat models (data not shown). Very transient increases in pro-inflammatory cytokines have been described a few hours following irradiation [3,5,18]. Therefore, plasma increases in pro-inflammatory cytokines may have occurred before our first measurement (24 hours post-irradiation). In contrast, we found significant plasma increases in Cytokine-Induced Neutrophil Chemoattractant-1 (CINC1/CXCL1) during both the acute and late phase after irradiation in our irradiated rat models (Fig. 6). CXCL1 belongs to the chemokine family. It is a major neutrophil chemoattractant and represents a reliable marker of inflammation [30,31]. Data from Fig. 6A indicates that CXCL1 plasma levels were strongly increased in both groups of irradiated rats 4 days post-irradiation, with the highest individual values found in rats with head protection. These results are in accordance with recent reports showing early increase in CXCL1 after irradiation [3,32]. However, increases in CXCL1 were also observed in the plasma of hind limbs- and head-protected irradiated rats in the late phase of irradiation. Data from Fig. 6B represents average values of CXCL1 plasma levels in control and irradiated animals between 21 and 71 days after irradiation (left panel) and at the very late phase after irradiation (between 50 and 64 days after irradiation, right panel). Results from Fig. 6B (left panel) indicate that CXCL1 plasma levels were significantly increased in both hind limbs- and head-protected rats between 21 and 71 days post-irradiation. In contrast, CXCL1 plasma levels were only found to be increased in head-protected rats at the very late phase of irradiation (between 50 and 64 days post-irradiation, Fig. 6B, right panel).

Bottom Line: To investigate the influence of cranial/brain irradiation on late visceral organ damage in case of high-dose exposure, Wistar rats were irradiated at 12 Gy, with either the head and fore limbs or the two hind limbs protected behind a lead wall (head- and hind limbs-protected respectively), which allows long-term survival thanks to bone marrow protection.Histological analysis performed at this time revealed that late damages to liver, kidney and ileum were attenuated in rats with head exposed when compared to animals whose head was protected.Altogether our results demonstrate the influence of cranial/brain exposure in the onset of organ damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiobiology, IRBA (Institut de Recherche Biomédicale des Armées), Brétigny-sur-Orge, France.

ABSTRACT
In case of high-dose radiation exposure, mechanisms controlling late visceral organ damage are still not completely understood and may involve the central nervous system. To investigate the influence of cranial/brain irradiation on late visceral organ damage in case of high-dose exposure, Wistar rats were irradiated at 12 Gy, with either the head and fore limbs or the two hind limbs protected behind a lead wall (head- and hind limbs-protected respectively), which allows long-term survival thanks to bone marrow protection. Although hind limbs- and head-protected irradiated rats exhibited similar hematopoietic and spleen reconstitution, a late body weight loss was observed in hind limbs-protected rats only. Histological analysis performed at this time revealed that late damages to liver, kidney and ileum were attenuated in rats with head exposed when compared to animals whose head was protected. Plasma measurements of inflammation biomarkers (haptoglobin and the chemokine CXCL1) suggest that the attenuated organ damage in hind limbs-protected rats may be in part related to reduced acute and chronic inflammation. Altogether our results demonstrate the influence of cranial/brain exposure in the onset of organ damage.

No MeSH data available.


Related in: MedlinePlus