The synthetic pyrethroid pesticide fenpropathrin (FEN) is extensively used worldwide and has frequently been detected in biota and the environment, whilst the negative effects and toxicological mechanisms of FEN on non-target organisms are still unknown. In the present study, healthy immature common carp were treated with FEN (0.45 and 1.35 μg/L) for a duration of 14 days, and the negative impacts and possible mechanisms of FEN on fish were investigated. Biochemical analyses results showed that FEN exposure altered the levels of glucose (GLU), total cholesterol (T-CHO), triglyceride (TG), albumin (ALB), alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) in carp serum, and caused histological injury of the liver and kidney, indicating that FEN may cause hepatotoxicity and nephrotoxicity in carp. In addition, FEN also altered the activities of superoxide dismutase (SOD) and catalase (CAT) in carp serum, upregulated the levels of reactive oxygen species (ROS), and elevated the levels of malondialdehyde (MDA) in the liver and kidney. Meanwhile, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were also upregulated, indicating that oxidative stress and inflammatory reaction may be involved in the hepatotoxicity and nephrotoxicity caused by FEN. Furthermore, RNA-seq analysis results revealed that FEN treatment induced a diverse array of transcriptional changes in the liver and kidney and downregulated differentially expressed genes (DEGs) were concentrated in multiple pathways, especially cell cycle and DNA replication, suggesting that FEN may induce cell cycle arrest of hepatocytes and renal cells, subsequently inducing hepatotoxicity and nephrotoxicity. Overall, the present study enhances our comprehension of the toxic effects of FEN and provides empirical evidence to support the risk assessment of FEN for non-target organisms.

Glyphosate (GLY) and microcystin-LR (MC-LR) frequently co-occur in natural water bodies. In this study, a subacute exposure test was conducted on zebrafish treated with 3.5 mg/L GLY and 35 μg/L MC-LR, individually and in combination, for 21 d to determine their effects on the gills of zebrafish and their potential mechanisms. The hematoxylin and eosin staining and scanning electron microscopy examination results showed that GLY and MC-LR exposure caused structural damage to gills. Biochemical analysis revealed Na⁺-K⁺-ATPase activity decreased, and the levels of reactive oxygen species, 8-hydroxy-2′-deoxyguanosine, and malondialdehyde increased, inducing oxidative damage to DNA and lipids of gills. Meanwhile, the inflammatory and immune function of the gill was significantly influenced, as evidenced by the alteration of the expression of tumor necrosis factor-α, interleukin-1β, complement 3, and immunoglobulin M. RNA-seq results revealed that GLY and/or MC-LR treatment induced transcriptional changes in the fish gills, which may affect various biological functions, and the lipid metabolism disruption potentially involved in the aforementioned process. Integrating histopathological, biochemical, and transcriptomic analyses, this study revealed that both individual and combined exposures to GLY and MC-LR had adverse effects on zebrafish gills, with combined exposure appears to result in more pronounced adverse effects, potentially compromising fish health.

Fine particulate matter (PM) 2.5 is the main component of air pollution causing pathological responses primarily in the respiratory and cardiovascular systems. Therefore, it is urgent to explore valid strategies to inhibit the adverse reactions induced by PM2.5. In our previous studies, we have revealed that intratracheal instillation of PM2.5 evoked airway remodeling, pulmonary inflammatory, and oxidative stress responses in rat lungs by upregulating VEGFA levels in bronchial epithelial cells and by activating ANGII/AT1R axis activation in vascular endothelial cells. The same results were obtained when human bronchial epithelial cells (Beas−2B) and human umbilical vein endothelial cells (HUVECs) cells were exposed to PM2.5 in vitro. Curcumin is a dietary polyphenol with protective properties, including anti−inflammatory and antioxidant effects. This study aims to determine the potential role of curcumin in protecting against PM2.5−induced adverse responses in the bronchial epithelium and vascular endothelium and the mechanism involved. To this end, we pretreated cells with curcumin (diluted 1000 times in sterile saline) for 2 h and then exposed them to PM2.5. Our results from RT−PCR, a luciferase reporter assay, and ELISA indicated that curcumin pretreatment effectively inhibited PM2.5−induced VEGFA elevation in Beas−2B cells by over 60% via blocking HIF1α accumulation and HIF1 transactivity, Moreover, curcumin also exerted a protective role in suppressing PM2.5−induced ANGII/AT1R axis components expression in HUVEC by over 90% via targeting the transcriptional factors, AP−1 and HIF1. Under the same conditions, curcumin pretreatment also blocked the downstream signaling events following ANGII/AT1R pathway activation, the increase in chemokines and cell adhesion molecules (sICAM−1, VCAM−1, E−Selectin, P−Selectin, IL−8, MCP−1) that drive monocyte−endothelial cell adhesion, as well as the elevated production of oxidative stress mediators (ROS and MDA) in HUVECs according to the data from immunofluorescence and flow cytometric assays. Most importantly, administration of curcumin resulted in an 80% reduction of the HIF1− and AP−1−dependent upregulation of VEGFA and AGT/AT1R axis components and impeding the resultant pro−inflammatory and oxidative responses in the lung of the rats exposed to PM2.5. Taking these data together, we disclosed the important role and mechanism of curcumin in protecting against PM2.5−induced adverse reactions in the bronchial epithelium and vascular endothelium. Curcumin might be used as a feasible and safe dietary agent to reduce the health risk of PM2.5.