Developmental neurotoxicity in the progeny after maternal gavage with chlorpyrifos

Today, developmental intellectual disorders affect one out of six children in industrialised countries. Intensively used in agriculture, the neurotoxicant pesticide chlorpyrifos (CPF) is known for its environmental persistence and bioaccumulation. Its role has not yet been established in the aetiology of intellectual impairments. Here we assessed whether maternal ingestion of low CPF dose in rats could impair the cerebral function of their progeny. Rat dams received daily CPF exposures (1 mg/kg, per os) during gestation and lactation. Behaviours relevant to mental retardation were measured in the surface righting, negative geotaxis and grip strength at post-natal days (PND) 3 and 7. Open field tests were performed at PND 16, 18 and 20. Fear conditioning was assessed at PND 34. Startle inhibition was tested at PND 31 and 60. According to the results, the progeny of CPF-treated dams showed slower negative geotaxis as neonates, lower novelty exploration as juveniles and faster startle reflex as adolescents and adults. This data suggests that developmental CPF relevant to human exposure may impair novelty-related activity and sensori-motor functions, thus adaptability to the environment. This data supports the hypothesis that CPF may contribute to behavioural disorders including acquisition retardation and consequences as an adult

New rat models of iron sucrose-induced iron overload

International audienceThe majority of murine models of iron sucrose-induced iron overload were carried out in adult subjects. This cannot reflect the high risk of iron overload in children who have an increased need for iron. In this study, we developed four experimental iron overload models in young rats using iron sucrose and evaluated different markers of iron overload, tissue oxidative stress and inflammation as its consequences. Iron overload was observed in all iron-treated rats, as evidenced by significant increases in serum iron indices, expression of liver hepcidin gene and total tissue iron content compared with control rats. We also showed that total tissue iron content was mainly associated with the dose of iron whereas serum iron indices depended essentially on the duration of iron administration. However, no differences in tissue inflammatory and antioxidant parameters from controls were observed. Furthermore, only rats exposed to daily iron injection at a dose of 75 mg/kg body weight for one week revealed a significant increase in lipid peroxidation in iron-treated rats compared with their controls. The present results suggest a correlation between iron overload levels and the dose of iron, as well as the duration and frequency of iron injection and confirm that iron sucrose may not play a crucial role in inflammation and oxidative stress. This study provides important information about iron sucrose-induced iron overload in rats and may be useful for iron sucrose therapy for iron deficiency anemia as well as for the prevention and diagnosis of iron sucrose-induced iron overload in pediatric patients

Food Contaminants Effects on an In Vitro Model of Human Intestinal Epithelium

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Dose- and Time-Dependent Effects of Radiofrequency Electromagnetic Field on Adipose Tissue: Implications of Thermoregulation and Mitochondrial Signaling

International audienceRecent studies have shed light on the effects of low-intensity radiofrequency (RF) fields on thermoregulation and adipose tissue metabolism. The present study aims to further explore these effects by analyzing the expression of thermoregulatory genes and investigating the involvement of mitochondria in adipose tissue metabolism. Male mice (n = 36 C57BL/6J) were assigned to either exposed or control groups. The exposed groups were subjected to RF fields at 900 MHz, with specific absorption rates (SAR) of 0.1 W/kg or 0.4 W/kg, either for three or seven consecutive days. The findings indicate that RF exposure leads to changes in adipose tissue markers, with some effects being dose-dependent and time-dependent. In brown adipose tissue (BAT), after 3 days of RF exposure, thermogenesis is reduced, mitochondrial activity in BAT decreases, and an increase in gene expression, responsible for balancing the regulatory and damaging effects of reactive oxygen species (ROS), was observed. This effect was partially compensated after 7 days of exposure. In white adipose tissue (WAT), RF exposure results in reduced fatty acid oxidation, impaired energy production, and hindered adipocyte differentiation. Notably, no effects of RF on mitochondrial biogenesis in WAT were observed. These findings contribute to understanding the effects of RF exposure on adipose tissue metabolism and thermoregulation, highlighting dose-dependent and time-dependent responses

How advanced are we on the consequences of oral exposure to food contaminants on the occurrence of chronic non communicable diseases?

International audienceThe development of an individual during fetal life and childhood is characterized by rapid growth as well as gradual maturation of organs and systems. Beyond the nutritional intake in essential nutrients, food contaminants can permanently influence the way organs mature and function. These processes are called "programming" and play an essential role in the occurrence of non-communicable chronic diseases throughout the lifespan. Populations as pregnant women, fetuses and young children are vulnerable and particularly sensitive to food contaminants which can induce epigenetic modifications transmissible to future generations. Among these contaminants, pesticides are found in most food matrices exposing humans to cocktails of molecules through variable concentrations and duration of exposure. The Maillard reaction products (MRPs) represent other food contaminants resulting from heat treatment of food. Modern diet, rich in fats and sugars, is also rich in neoformed pathogenic compounds, Advanced Glycation End products (AGEs), the levels of which depend on the heat treatment of foods and eating habits and whose effects on health are controversial. In this review, we have chosen to present the current knowledge on the impacts of selected pesticides and MRPs, on the risk of developing during life non-communicable chronic diseases such as IBD, metabolic disorders or allergies. A large review of literature was performed via Pubmed, and the most appropriate studies were summarised

Programmation de l'homéostasie intestinale chez la descendance male exposée au chlorpyriphos et/ou un régime obésogène.

International audienceAbstract Alteration of programming of the intestinal wall maturation may be responsible for non-communicable chronic diseases in adulthood. It may originate from prenatal exposure of mothers to deleterious environmental factors such as pesticides or western diet. This work was undertaken to determine whether disturbances of the digestive tract function and of innate immunity of offspring at adulthood could be due to maternal exposure to a pesticide, chlorpyrifos (CPF) and a High Fat Diet (HFD) starting 4 months before gestation and lasting until weaning of offspring. Fifty-one male Wistar rats coming from 4 groups of dams exposed to CPF, HFD, both and control were followed from birth to 8 weeks of age. They were fed standard chow and received no treatment. The maternal pesticide exposure slows down fetal and postnatal weight gain without histological injuries of the gut mucosa. CPF or HFD both induced modifications of tight junctions and mucins genes expressions without inducing an increase in epithelial permeability or an inflammatory state. Co-exposure to both CPF and HFD did not exacerbate the effects observed with each factor separately. Despite the lack of direct contact except through breast milk until weaning, CPF or HFD maternal exposure have demonstrated preliminary gut barrier impacts on offspring