Modification des récepteurs cholinergiques de type nicotinique par des doses sublétales d'imidaclopride chez la blatte Periplaneta americana

Les insecticides néonicotinoïdes sont une classe d\u27insecticides utilisée pour contrôler les insectes ravageurs de cultures. Ces molécules miment l\u27effet de l\u27acétylcholine (ACh) en agissant comme des agonistes des récepteurs cholinergiques de type nicotinique (nAChRs) au niveau du système nerveux central des insectes. Suite à l\u27utilisation des néonicotinoïdes ces dernières années, des phénomènes de résistance ont été révélés chez beaucoup d\u27espèces. Ces phénomènes menacent d\u27une part l\u27agriculture et d\u27autre part la santé publique. Afin de comprendre les facteurs impliqués dans les phénomènes de résistance aux néonicotinoïdes, nous avons étudié les mécanismes d\u27adaptation développés suite à une exposition chronique à des doses sublétales de néonicotinoïde. Dans un premier temps, nous avons étudié la toxicité d\u27une molécule néonicotinoïde (l\u27imidaclopride) chez la blatte Periplaneta americana . Ensuite, l\u27effet d\u27une exposition chronique à une dose sublétale d\u27imidaclopride a été exploré sur neurones DUM (Dorsal Unpaired Median) de la blatte grâce à la technique électrophysiologique de patch - clamp, dans des conditions de potentiel imposé. Les premiers résultats obtenus montrent que cette exposition chronique peut modifier le profil pharmacologique des nAChRs au niveau des neurones DUM. En effet, une diminution de la sensibilité à l\u27imidaclopride des nAChRs a été mise en évidence. Dans un deuxième temps, nous avons montré en PCR quantitative que la diminution de la sensibilité des nAChRs pourrait avoir un lien avec une modification du niveau d\u27expression des différentes sous – unités qui composent ces récepteurs

Bilirubin decreases NOS2 expression via inhibition of NAD(P)H oxidase: implications for protection against endotoxic shock in rats.

We investigated a possible beneficial role for bilirubin, one of the products of heme degradation by the cytoprotective enzyme heme oxygenase-1 in counteracting Escherichia coli endotoxin-mediated toxicity. Homozygous jaundice Gunn rats, which display high plasma bilirubin levels due to deficiency of glucuronyl transferase activity, and Sprague-Dawley rats subjected to sustained exogenous bilirubin administration were more resistant to endotoxin (LPS)-induced hypotension and death compared with nonhyperbilirubinemic rats. LPS-stimulated production of nitric oxide (NO) was significantly decreased in hyperbilirubinemic rats compared with normal animals; this effect was associated with reduction of inducible NO synthase (NOS2) expression in renal, myocardial, and aortic tissues. Furthermore, NOS2 protein expression and activity were reduced in murine macrophages stimulated with LPS and preincubated with bilirubin at concentrations similar to that found in the serum of hyperbilirubinemic animals. This effect was secondary to inhibition of NAD(P)H oxidase since 1) inhibition of NAD(P)H oxidase attenuated NOS2 induction by LPS, 2) bilirubin decreased NAD(P)H oxidase activity in vivo and in vitro, and 3) down-regulation of NOS2 by bilirubin was reversed by addition of NAD(P)H. These findings indicate that bilirubin can act as an effective agent to reduce mortality and counteract hypotension elicited by endotoxin through mechanisms involving a decreased NOS2 induction secondary to inhibition of NAD(P)H oxidase

Oxidative stress targets in pulmonary emphysema: focus on the Nrf2 pathway

IMPORTANCE OF THE FIELD: Oxidative stress has been implicated in the pathogenesis of pulmonary emphysema. Nuclear factor erythroid-2-related factor 2 (Nrf2) a major antioxidant transcription factor could play a protective role in pulmonary emphysema. AREAS COVERED IN THIS REVIEW: Nrf2 is ubiquitously expressed throughout the lung, but is predominantly found in epithelium and alveolar macrophages. Evidence suggests that Nrf2 and several Nrf2 downstream genes have an essential protective role in the lung against oxidative stress from environmental pollutants and toxicants such as cigarette smoke, a major causative factor for the development and progression of pulmonary emphysema. Application of Nrf2-deficient mice identified an extensive range of protective roles for Nrf2 against the pathogenesis of pulmonary emphysema. Therefore, Nrf2 promises to be an attractive therapeutic target for intervention and prevention strategies. WHAT THE READER WILL GAIN: In this review, we discuss recent findings on the association of oxidative stress with pulmonary emphysema. We also address the mechanisms of Nrf2 lung protection against oxidative stress based on emerging evidence from experimental oxidative disease models and human studie. TAKE HOME MESSAGE: The current literature suggests that among oxidative stress targets, Nrf2 is a valuable therapeutic target in pulmonary emphysema