Inflammatory and cytotoxic effects of bifenthrin in primary microglia and organotypic hippocampal slice cultures

Abstract

BackgroundPyrethroids, such as bifenthrin (BF), are among the most widely used class of insecticides that pose serious risks to human and wildlife health. Pyrethroids are proposed to affect astrocytic functions and to cause neuron injury in the central nervous system (CNS). Microglia are key cells involved in innate immune responses in the CNS, and microglia activation has been linked to inflammation and neurotoxicity. However, little information is known about the effects of BF-induced toxicity in primary microglial cells as well as in organotypic hippocampal slice cultures (OHSCs).MethodsOxidative stress and inflammatory responses induced by BF were evaluated in primary microglial cells and OHSCs incubated with different concentrations of BF (1–20 μM) for 4 and 24 h. mRNA and protein synthesis of cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), nuclear erythroid-2 like factor-2 (Nrf-2), and microsomal prostaglandin synthase-1 (mPGES-1) was also studied by qPCR and Western blot. Cell viability was analyzed by MTT-tetrazolio (MTT) and lactate dehydrogenase (LDH) assays. Neurotoxicity in OHSCs was analyzed by propidium iodide (PI) staining and confocal microscopy.ResultsExposure of microglial cells to BF for 24 h resulted in a dose-dependent reduction in the number of viable cells. At sub-cytotoxic concentrations, BF increased reactive oxygen species (ROS), TNF-alpha synthesis, and prostaglandin E2 (PGE2) production, at both 4- and 24-h time points, respectively. Furthermore, BF incubation decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and increased lipid peroxidation, protein oxidation, and H2O2 formation. In addition, BF significantly induced protein synthesis and mRNA expression of oxidative and inflammatory mediators after 4 and 24 h, including Nrf-2, COX-2, mPGES-1, and nuclear factor kappaB (NF-kappaB). A 24-h exposure of OHSCs to BF also increased neuronal death compared to untreated controls. Furthermore, depletion of microglia from OHSCs potently enhanced neuronal death induced by BF.ConclusionsOverall, BF exhibited cytotoxic effects in primary microglial cells, accompanied by the induction of various inflammatory and oxidative stress markers including the Nrf-2/COX-2/mPGES-1/NF-kappaB pathways. Moreover, the study provided evidence that BF induced neuronal death in OHSCs and suggests that microglia exert a protective function against BF toxicity.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1198-1) contains supplementary material, which is available to authorized users.

Transcriptomic and Histopathological Effects of Bifenthrin to the Brain of Juvenile Rainbow Trout (Oncorhynchus mykiss)

“…Dysregulated pathways involved in maintaining structural stability of the extracellular matrix and impaired focal adhesion in the brains of bifenthrin-exposed trout are consistent with oxidative stress induced effects previously observed in neuronal in vitro cell lines and in murine, in vivo-based studies, following bifenthrin treatment [51][52][53][54], though, interestingly, oxidative stress genes were not differentially altered in bifenthrin treatment groups, relative to controls. Similarly, we previously reported that steelhead trout exposed to 60 and 120 ng/L bifenthrin were predicted to have induced reactive oxygen species production due to oxidative stress, and subsequently observed apoptotic effects driven by altered levels of metabolites [23].…”

Effect of Lambdacyhalothrin on Locomotor Activity, Memory, Selected Biochemical Parameters, Tumor Necrosis Factor α, and Interleukin 1ß in a Mouse Model

“…There are many reports confirming that exposure on pyrethroids causes oxidative stress and in this mechanism causes an increase in the expression of genes encoding proinflammatory cytokines [ 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The interleukin1β is primarily synthesized in macrophages and monocytes.…”

Buprofezin toxication implicates health hazards in Nile tilapia ( Oreochromis niloticus )

“…In the present study, the expression of COX-2 gene, revealed significant elevations in liver and muscle of treated fish in comparison with the control group. Similarly, Gargouri, Yousif, Bouchard, Fetoui, and Fiebich (2018) showed that exposure of microglial cells to buprofezin, in vitro, resulted in significant induction of protein synthesis and mRNA expression of COX-2.…”