Comparative Biochemistry and Physiology C-toxicology & Pharmacology最新文献

High-sugar diets (HSD) represent a pervasive environmental stressor with significant health risks, yet the comparative toxicology and underlying molecular mechanisms of its impact on the central nervous system remain poorly understood. This study investigated the neurobehavioral toxicity of HSD and elucidated its mechanism of action, utilizing the invertebrate model Drosophila melanogaster to explore conserved physiological responses. Chronic exposure to a 20% HSD induced significant sleep impairment, a key neurobehavioral endpoint, characterized by reduced total sleep time and increased activity duration without affecting core circadian rhythmicity. Mechanistically, we identified a novel, indirect neurotoxic pathway originating in the gut, highlighting a conserved gut-brain axis. HSD exposure acted as a potent disruptor of gut homeostasis, inducing microbiota dysbiosis (notably decreasing Acetobacter aceti abundance) and triggering a robust intestinal inflammatory response, marked by the upregulation of pro-inflammatory cytokines Upd3 and Eiger (homologs of mammalian IL-6 and TNF-α). This peripheral immunotoxicity was causally linked to central neurochemical disruption, leading to significant neurotransmitter imbalances in the brain. Critically, targeting the initial site of toxicity-the gut-by genetically reducing Upd3 or Eiger expression specifically in intestinal epithelial cells was sufficient to rescue both the sleep deficits and the altered neurotransmitter profiles. Furthermore, ameliorating gut dysbiosis via dietary supplementation with A. aceti reversed the intestinal inflammation and normalized sleep behavior. These findings demonstrate that HSD exerts its neurobehavioral toxicity through a conserved gut-brain axis mechanism, where microbiota dysbiosis and intestinal inflammation drive central neurotransmitter dysregulation. This work highlights a critical toxicological pathway for dietary stressors with broad comparative and physiological relevance and identifies the gut inflammatory axis as a potential therapeutic target.

Microplastics have been established as a novel environmental contaminant, while bisphenol A represents a common endocrine-disrupting chemical. However, the combined toxicity of both pollutants on the gills of marine crustaceans remains underexplored. This study investigated the possible risks associated with co-exposure to MPs and BPA on the gills of Portunus trituberculatus. Crabs were exposed to 100 μg/L BPA, 10 mg/L MPs, and a combination of 100 μg/L BPA + 10 mg/L MPs for 21 days. Histological analysis revealed that both MPs and BPA significantly compromised gill architecture. Transcriptomic analysis identified 1766 differentially expressed transcripts under varying exposure conditions, which were implicated in biological processes associated with oxidative stress, ion regulation, and apoptosis. The presence of MPs, BPA, and their co-exposure resulted in a reduction of sodium/potassium-transporting ATPase subunit beta-1 expression levels, ATPase activities, ATP content, and ion concentrations in the gills when compared to the control group. Notably, MPs, BPA and their combined treatment induced ROS and H₂O₂ accumulation, and the upregulation of catalase and superoxide dismutase activities, which could potentially impact cell apoptosis. These results suggest that MPs and BPA may adversely affect oxidative damage, ion content, ion regulatory proteins, ion transport ATPase activity, apoptosis and their related gene expression in the gills of P. trituberculatus. Besides, integrated biomarker response values indicated that co-treatment resulted in greater gill toxicity. This comprehensive understanding highlights the imperative for preemptive measures to mitigate the adverse effects of environmental pollutants on ecological health, while providing valuable insights into the relevant molecular pathways.

Microplastics (MPs) are pervasive environmental pollutants, accumulating in ecosystems and posing a long-term exposure risk to both the entire ecosystem and human health. However, the combined impact of such high doses on insect longevity and the consequent ecological consequences remain understudied. Here we used Drosophila melanogaster as a model to quantify lifespan shortening under environmentally realistic and extreme concentrations of Polyethylene (PE) and Polystyrene (PS) co-exposures and to unravel the molecular bases of the observed toxicity. Furthermore, we delved into the underlying mechanism through metabolomics and transcriptomics analysis. Our results demonstrated PE and PS MPs co-exposure with greatly high concentrations significantly reduced the lifespan of Drosophila and influenced age-related phenotypes such as climbing ability, intestinal barrier and hunger resistance. We found that differential metabolites were engaged in various metabolic pathways, including ABC transporters, alanine, aspartate and glutamate metabolism. Differentially expressed genes (DEGs) were closely related to Toll and Imd signaling pathway and Longevity regulating pathway. Gram-level PE and PS co-exposure triggers immune-metabolic crosstalk failure and represents a realistic terrestrial risk factor for insect longevity. Our data highlight the urgent need to include high-dose microplastic mixtures in terrestrial ecotoxicological risk assessments and biodiversity conservation strategies. SYNOPSIS: Co-exposure to PE and PS MPs with high concentrations induces changes in gene expression and metabolites associated with immune system and energy metabolism in Drosophila, thereby affecting their lifespan.

Rare earth elements (REEs) are collectively referred to as scandium, yttrium and 15 lanthanide metals in the periodic table. Due to their unique photoelectric and magnetic properties, they are widely used in permanent magnets, new energy and cutting-edge defense technologies. However, large-scale mining and utilization of REEs have led to a significant increase in their concentration in the environment. In the environment, these REEs are regarded as emerging contaminants (ECs). Erbium (Er), a rare earth element of the lanthanide series, is widely used in ceramics, optical fibers, and the nuclear industry. Currently, research on the ecotoxicity of erbium is limited, and its target organs of action remain unclear. In this study, zebrafish were used as experimental animals, and acute exposure experiments were conducted by exposing 72 hpf zebrafish larvae to different concentrations of erbium chloride solution to explore the ecotoxicity of erbium. The main research results are as follows: (1) Exposure to erbium causes abnormal liver development in zebrafish larvae and the liver area of the erbium-exposed group was smaller than that of the control group. (2) Erbium affects liver lipid metabolism, leading to lipid accumulation in the liver of zebrafish larvae, and increasing the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC) and triglycerides (TG). (3) Exposure to erbium leads to an increase in ROS levels in the liver, and the upregulated expression of the sod1 and sod2 genes. (4) The Keap1/Nrf2 pathway inhibitor resveratrol can effectively alleviate liver lipid accumulation, reduce oxidative stress in the liver and alleviate the liver damage induced by erbium. This study discovered that erbium causes abnormal liver function in zebrafish larvae, suggesting that it might cause liver damage in zebrafish through the ROS-mediated Keap1/Nrf2 pathway. These findings contribute to a more comprehensive understanding of the impact of rare earth elements on the ecosystem and provide a scientific basis for related environmental protection policies.

Global warming alters the toxicity and bioavailability of environmental pollutants in aquatic ecosystems. Methylmercury (MeHg), a highly toxic form of mercury, poses significant risks, yet its interaction with temperature remains understudied. Thus, this study aims to understand how elevated temperature affects the physiological and molecular toxicity of MeHg exposure in aquatic invertebrates. We investigated the combined effects of elevated temperature (23 and 28 °C) and MeHg (10 and 50 ng/L) on the freshwater invertebrate Daphnia magna. Acute toxicity was significantly enhanced at 28 °C. Chronic exposure reduced survival, reproduction, and growth, particularly under combined elevated temperature and MeHg conditions. While mercury accumulation increased with MeHg concentration, temperature did not influence internal Hg levels. Biochemical analyses showed that elevated temperature reduced ROS levels but increased antioxidant enzyme activity, whereas antioxidant gene expression was suppressed. MeHg exposure inhibited acetylcholinesterase activity, with greater inhibition observed under combined exposure. Detoxification responses were temperature-specific. Glutathione-mediated system was activated at 28 °C. ABCC activity increased with temperature and MeHg, whereas ABCB activity was suppressed at 28 °C, but partially recovered with MeHg. These findings demonstrate that elevated temperature amplifies MeHg toxicity through physiological and molecular disruptions and emphasize the value of considering temperature-pollutant interactions in ecological risk assessments under climate change scenarios.