Effect of repetitive potassium iodide on elderly rat’s thyroid

Background: Nuclear power plant emergencies had often been accompanied by radioactivity release into the environment, thyroid cancer is one of the major health consequences due to the effect of radioactive iodine (131I) that emits ϒ ray and β particles resulting in thyroid DNA damage and late onset thyroid cancer. Intake of a single dose of potassium iodide (KI) is recommended to reduce this risk. However in case of prolonged radioiodine release as noticed during Chernobyl and Fukushima accidents, more than one dose of KI may be basic to ensure adequate protection [1]. Whereas a single dose of KI is admitted to be safe, knowledge about the effects of repeated KI administration are scarce, few studies demonstrated the potential efficiency of repetitive KI intake in humans [2] and non-human primates [3] without hormonal variations. These studies are relevant in the field of radiation protection and give a base evidence of the possible use of repetitive KI. On the other hand, we have studies on rodents that showed an impact of chronic iodine excess on pituitary thyroid axis function [4]. Our previous work on adult male rats demonstrated the safety of repeated administration of KI over 8 days [5]. Indeed in the elderly persons KI administration in case of nuclear emergency remains a topic of debate, because of the possible impact in cardiovascular diseases. Thyroid hormones are well-known for their profound effects on cardiovascular function and metabolism; myocardial and vascular endothelial tissues have receptors for thyroid hormones and are sensitive even to subtle changes in the concentrations of circulating pituitary and/or thyroid hormones i.e. subclinical hypothyroidism and hyperthyroidism. It is well established that hyperthyroidism induces a hyper-dynamic cardiovascular state, which is associated with a faster heart rate, enhanced left ventricular systolic and diastolic function whereas hypothyroidism is characterized by the opposite changes. Atrial fibrillation is the most common cardiac arrhythmia in the elderly, the prevalence and incidence increase with advancing age [6]. Several interventional trials showed that treatment of subclinical thyroid diseases improves cardiovascular risk factors, which implies potential benefits for reducing cardiovascular events. Objective: The aim of this study is to assess the effects of repeated KI intake on the thyroid function of aged male rats. Methods: A twelve months old male rats were subjected to either KI or saline solution over 8 days. Clinical biochemistry, pituitary and thyroid hormones level, and thyroid genes expression were analyzed 30 days after the treatment discontinuation. Findings: urinary assessment shows a subtle increase of some parameters (Creatinin, Uric Acid, Urea, Glucose, Potassium, Sodium and Chlorine), plasma biochemistry reveals a subtle variation of some parameters (an increase of Creatinin, Glucose and phosphorus; and a decrease of Chlorine level). Regarding pituitary-thyroid hormones we get a significant decrease of TSH level without thyroid hormones variation. At the molecular level, we observe a significant increase of TPO (+100%), AIT (+299%) and Tg (+38%) mRNA expression. On the other hand we get a significant decrease of TSHR (-51%) mRNA expression. Conclusion and perspectives: Our first results indicate that repeated KI intake affects the clinical biochemistry and the pituitary-thyroid axis function in elderly rats. To go further we are investigating the impact of these variations on the cardiovascular function and its parameters. Cardiac output data, cardiovascular gene expression, oxidative stress and inflammatory analysis are being processed. This study will contribute to the evolution of iodine policy and the harmonization of the current KI guidelines

Analyse des effets des rayonnements ionisants sur le système nerveux central du poisson zèbre : de la molécule à l’individu

Emerging evidence describe neurological effects on adult exposure to radiation at dose rates much lower than previously thought in humans including elevated risk of Parkinson’s disease and cerebrovascular defects. The alteration of central nervous system integrity caused by chronic exposure to low to moderate dose rates of IR could thus affect major processes such as reproduction and behavior. To evaluate the impact of IR on adult brain zebrafish, we exposed the whole organisms to three dose rates (0,05 mGy.h-1; 0,5 mGy.h-1 et 5 mGy.h-1) for 36 days. Transcriptomic studies associated with RNA in situ hybridization analysis showed the increased expression of genes with function in neurotransmission or stress and identified potential biomarkers (oxytocin, arginin-vasopressin, cone rod homeobox) specific to ionizing radiation exposure compared to physical injury through stabwound. In our experimental conditions, we observed the induction of neurogenesis contrarily to the impact of acute and high doses of IR where neurogenesis is reduced. While after stabwound injury, reactive neurogenesis is dependent on inflammatory processes, here neuro-inflammation was not initiated thus proposing a compensative system through potential anti-oxidative action of oxytocin and the anti-inflammatory role of cortisol. These modifications on the molecular scale impacted the behavioral response specifically on female zebrafish with increased stress and reduction of sociability. Altogether, these findings highlight the intricate interaction between neurohormones, neurotransmission and neurogenesis process to balance the disturbed brain homeostasis caused by our experimental conditionsDe récentes études attestent de l’apparition d’effets neurologiques chez l’adulte tels qu’une augmentation du risque d’apparition de la maladie de Parkinson ou des défauts cérébrovasculaires associés à une exposition à des faibles débits de dose de rayonnements ionisants. Une altération de l’intégrité du système nerveux central lors d’une exposition chronique à faibles doses de RI serait donc susceptible d’affecter des processus majeurs comme la survie, la reproduction et le comportement. Afin d’évaluer l’impact des radiations sur le cerveau du poisson zèbre adulte, trois débits de doses (0,05 mGy.h-1 ; 0,5 mGy.h-1 et 5 mGy.h-1) ont été retenus et maintenus durant 36 jours. Grâce à des études transcriptomiques complétées d’hybridations d’ARN in situ, nous avons observé l’augmentation de l’expression de gènes impliqués dans la neurotransmission, dans l’axe du stress et identifié de potentiels biomarqueurs (ocytocine, arginine-vasopressine, cone rod homeobox) spécifiques d’une réponse aux expositions des RI en comparaison avec la blessure physique du stabwound. A contrario des fortes doses de RI (diminution de neurogenèse) et similairement au stabwound, l’induction de la neurogenèse dans nos conditions expérimentales suggère la mise en place d’une compensation. Ces modifications à l’échelle moléculaire ont entrainé des perturbations comportementales, en particulier l’initiation d’un stress et la diminution de la réponse sociale chez les femelles. Ces travaux soulignent l’interaction complexe entre neurohormones, neurotransmetteurs et processus de neurogenèse afin de compenser les perturbations causées et modifiant l’homéostasie cérébrale dans nos conditions expérimentale

Impact of chronic exposure to low to moderate dose rates of ionizing radiation on the brain of adult zebrafish

De récentes études attestent de l’apparition d’effets neurologiques chez l’adulte tels qu’une augmentation du risque d’apparition de la maladie de Parkinson ou des défauts cérébrovasculaires associés à une exposition à des faibles débits de dose de rayonnements ionisants. Une altération de l’intégrité du système nerveux central lors d’une exposition chronique à faibles doses de RI serait donc susceptible d’affecter des processus majeurs comme la survie, la reproduction et le comportement. Afin d’évaluer l’impact des radiations sur le cerveau du poisson zèbre adulte, trois débits de doses (0,05 mGy.h-1 ; 0,5 mGy.h-1 et 5 mGy.h-1) ont été retenus et maintenus durant 36 jours. Grâce à des études transcriptomiques complétées d’hybridations d’ARN in situ, nous avons observé l’augmentation de l’expression de gènes impliqués dans la neurotransmission, dans l’axe du stress et identifié de potentiels biomarqueurs (ocytocine, arginine-vasopressine, cone rod homeobox) spécifiques d’une réponse aux expositions des RI en comparaison avec la blessure physique du stabwound. A contrario des fortes doses de RI (diminution de neurogenèse) et similairement au stabwound, l’induction de la neurogenèse dans nos conditions expérimentales suggère la mise en place d’une compensation. Ces modifications à l’échelle moléculaire ont entrainé des perturbations comportementales, en particulier l’initiation d’un stress et la diminution de la réponse sociale chez les femelles. Ces travaux soulignent l’interaction complexe entre neurohormones, neurotransmetteurs et processus de neurogenèse afin de compenser les perturbations causées et modifiant l’homéostasie cérébrale dans nos conditions expérimentalesEmerging evidence describe neurological effects on adult exposure to radiation at dose rates much lower than previously thought in humans including elevated risk of Parkinson’s disease and cerebrovascular defects. The alteration of central nervous system integrity caused by chronic exposure to low to moderate dose rates of IR could thus affect major processes such as reproduction and behavior. To evaluate the impact of IR on adult brain zebrafish, we exposed the whole organisms to three dose rates (0,05 mGy.h-1; 0,5 mGy.h-1 et 5 mGy.h-1) for 36 days. Transcriptomic studies associated with RNA in situ hybridization analysis showed the increased expression of genes with function in neurotransmission or stress and identified potential biomarkers (oxytocin, arginin-vasopressin, cone rod homeobox) specific to ionizing radiation exposure compared to physical injury through stabwound. In our experimental conditions, we observed the induction of neurogenesis contrarily to the impact of acute and high doses of IR where neurogenesis is reduced. While after stabwound injury, reactive neurogenesis is dependent on inflammatory processes, here neuro-inflammation was not initiated thus proposing a compensative system through potential anti-oxidative action of oxytocin and the anti-inflammatory role of cortisol. These modifications on the molecular scale impacted the behavioral response specifically on female zebrafish with increased stress and reduction of sociability. Altogether, these findings highlight the intricate interaction between neurohormones, neurotransmission and neurogenesis process to balance the disturbed brain homeostasis caused by our experimental condition

Revealing the Increased Stress Response Behavior through Transcriptomic Analysis of Adult Zebrafish Brain after Chronic Low to Moderate Dose Rates of Ionizing Radiation

International audienceHigh levels of ionizing radiation (IR) are known to induce neurogenesis defects with harmful consequences on brain morphogenesis and cognitive functions, but the effects of chronic low to moderate dose rates of IR remain largely unknown. In this study, we aim at defining the main molecular pathways impacted by IR and how these effects can translate to higher organizational levels such as behavior. Adult zebrafish were exposed to gamma radiation for 36 days at 0.05 mGy/h, 0.5 mGy/h and 5 mGy/h. RNA sequencing was performed on the telencephalon and completed by RNA in situ hybridization that confirmed the upregulation of oxytocin and cone rod homeobox in the parvocellular preoptic nucleus. A dose rate-dependent increase in differentially expressed genes (DEG) was observed with 27 DEG at 0.05 mGy/h, 200 DEG at 0.5 mGy/h and 530 DEG at 5 mGy/h. Genes involved in neurotransmission, neurohormones and hypothalamic-pituitary-interrenal axis functions were specifically affected, strongly suggesting their involvement in the stress response behavior observed after exposure to dose rates superior or equal to 0.5 mGy/h. At the individual scale, hypolocomotion, increased freezing and social stress were detected. Together, these data highlight the intricate interaction between neurohormones (and particularly oxytocin), neurotransmission and neurogenesis in response to chronic exposure to IR and the establishment of anxiety-like behavior

Effect of repetitive potassium iodide on elderly rat’s thyroid

Background: Nuclear power plant emergencies had often been accompanied by radioactivity release into the environment, thyroid cancer is one of the major health consequences due to the effect of radioactive iodine (131I) that emits ϒ ray and β particles resulting in thyroid DNA damage and late onset thyroid cancer. Intake of a single dose of potassium iodide (KI) is recommended to reduce this risk. However in case of prolonged radioiodine release as noticed during Chernobyl and Fukushima accidents, more than one dose of KI may be basic to ensure adequate protection [

Effect of repetitive potassium iodide on thyroid and cardiovascular functions in elderly rats

International audienceBackground: To date, paediatric thyroid cancer has been the most severe health consequence of the Chernobylaccident, caused by radioactive iodine (131I) aerosol’s dispersion. WHO recommends a single dose of potassiumiodide (KI) to reduce this risk. Following the Fukushima accident, it became obvious that repetitive doses of KImay be necessary due to multiple exposures to 131I. Knowledge about the effects of repeated ITB (Iodine ThyroidBlocking) is scarce and controversial. KI may affect the thyroid hormones synthesis; which is crucial for thecardiovascular function. Furthermore, myocardial and vascular endothelial tissues are sensitizes to subtlechanges at the concentration of circulating pituitary and/or thyroid hormones.Objective: In this preclinical study, we aimed to assess the effects of repeated ITB in elderly male rats.Methods: Twelve months old male Wistar rats were subjected to either KI or saline solution for eight days. Analyses were performed 24 h and 30 days after the treatment discontinuation.Findings: We reported a significant increase (18%) in some urinary parameters related to renal function, a subtledecrease of plasma TSH level, a significant increase (379%) in renin and a significant decrease (50%) in aldosterone upon KI administration. At the molecular level, the expression of thyroid and cardiovascular genes wassignificantly affected by the treatment. However, in our experimental settlement, animal heart rate was notsignificantly affected thirty days after KI discontinuation. ECG patterns did not change after administration of KI,and arrhythmia was not observed in these conditions despite the PR-intervals decreased significantly. Cardiovascular physiology was preserved.Conclusion: Our results indicate that repeated ITB in elderly rats is characterized by molecular modifications ofcardiovascular key actors, particularly the Renin-angiotensin-aldosterone axis with a preserved physiologicalhomeostasis. This new scientific evidence may be useful for the maturation of ITB guidelines especially forelderly sub-population