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

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with identified etiological mechanisms, yet effective treatments remain elusive. Individuals with ASD often exhibit compromised antioxidant defenses and are subject to oxidative stress. In this study, we used an established zebrafish (Danio rerio) model of autism with valproic acid (VPA) and subsequently administered 20 μg/mL Alpha-lipoic acid (ALA) to assess its effects on oxidative stress markers, transcriptional alterations in genes associated with autism, inflammatory mediators, apoptosis, the hypothalamic-pituitary-interrenal (HPI) axis, and aggressive behavior. Our results demonstrated that ALA treatment significantly enhanced the activity of antioxidant enzymes, particularly glutathione S-transferase (GST) and glutathione peroxidase (GPX), while increasing glutathione (GSH) levels and reducing malondialdehyde (MDA) concentrations. ALA treatment resulted in lower expression levels of inflammatory cytokines TNF-α and IL-6 mRNA. ALA downregulated the expression of apoptotic markers such as caspase-3, caspase-8, and caspase-9, as well as decrease the number of apoptotic cells. Additionally, behavioral assessments indicated a restoration of aggressive behavior, alongside a reduction in the expression of HPI axis-related hormones, including CRHα, CRHβ, UI, GR and MR, leading to decreased systemic cortisol level. Furthermore, ALA treatment reduced the expression of autism-related genes like shank3a, chd8, adsl, and mbd5. Molecular docking analyses suggest ALA may directly interact with proteins from these genes, offering new insights into its role in autism-related pathways. Collectively, our findings suggest that ALA may mitigate VPA-induced ASD-like symptoms by enhancing antioxidant capacity, alleviating oxidative stress, modulating inflammatory responses, and repressing apoptotic and HPI axis activity, thereby offering a potential therapeutic avenue for the management of ASD symptoms.

Cyhalothrin is a neurotoxicant that elicits neurotoxicity by targeting voltage-gated sodium channels of nontarget species, leading to damaging neurotoxic effects. However, little has been reported on cyhalothrin's neurotoxicity in zebrafish; hence, the present study utilized zebrafish embryos to larvae to investigate cyhalothrin's neurotoxicity and mechanisms, employing multi-biomarker analysis. Behavioral analysis showed cyhalothrin altered the spontaneous activities of the embryos by eliciting hyperactivity and causing hypoactivity in larval locomotor movement. Biochemical analysis revealed modifications in the content of GABA, TNF-α, IL-1β, ROS and GSH. Histological examinations of the larval head and trunk tissues saw severe nuclei karyolysis and pyknosis, and infiltration of inflammatory cells, signifying cellular damage. RNA-sequencing of larval mRNA showed that cyhalothrin exposure caused upregulation of 525 differentially expressed genes (DEGs) and downregulation of 516 DEGs. It also disrupted gene expression in nervous and developmental systems, indicated by GO/KEGG pathways. Mechanism findings revealed that it regulated the gene expression levels of NF-κB (tnfa, il1b, map3k14a, nfkbiaa, nfkbiab and tnfrsf1a) and L-Glutamate signaling pathway (slc6a19a.2, slc1a5, si:ch1073-155 h21.2 and gls2a) to impair the GABA secretion. The results of molecular docking indicate that TNFα and IL1β binds more tightly to cyhalothrin in the NF-κB pathway and generate inflammation. The results showed that cyhalothrin elicited neurotoxicity in the zebrafish embryo, and the possible mechanism is that it induced inflammation, which in turn disorder GABA secretion. It may be utilized for evaluating zebrafish health and neurological disease studies.

Global expansion of saline-alkaline waters renders carbonate alkalinity a critical environmental stressor for fish. This study investigated the hepatic physiological and metabolic responses of grass carp to chronic carbonate alkalinity exposure (20 (T) and 40 (F) mmol/L NaHCO₃) using growth performance assessment, biochemical assays, and untargeted metabolomics. The results demonstrated that carbonate alkalinity exposure significantly depressed growth performance, and induced oxidative stress. Compared to the Con group, hepatic ammonia and urea contents in the T and F groups were elevated by 38.4% and 82.9% (P < 0.0001), and by 26.4% (P < 0.0001) and 49.1% (P < 0.0001), respectively. Notably, ATP content decreased significantly by 21.5% and 47.1% (P < 0.0001) in the T and F groups, respectively. Combined with metabolomics results, the elevation in ammonia content likely triggered the activation of the Glu-Gln pathway and urea cycle for compensatory ammonia detoxification; however, this process imposes a heavy energy metabolic load due to high ATP consumption. The activation of purine metabolism provided evidence for the energy crisis, and the generation of ROS during this process is likely closely involved in the induction of oxidative stress. Furthermore, the upregulation of unsaturated fatty acid biosynthesis appears to be an adaptive metabolic reprogramming strategy to maintain membrane fluidity and provide substrates for subsequent energy metabolism. In conclusion, the remodeling of the hepatic metabolic network in grass carp induced by carbonate alkalinity exposure is a comprehensive regulatory process involving nitrogen, energy, and lipid metabolism, coupled with the antioxidant system.

Rising seawater temperatures fundamentally reshape marine ecosystems, with the Southern Ocean exhibiting vulnerability to climatic perturbations. Antarctic teleosts have evolved under near-constant sub-zero conditions, developing unique physiological adaptations. In this study, responses of Trematomus bernacchii, an endemic Antarctic fish, to three successive marine heatwave-like events were addressed. Using implantable bio-loggers, core body temperature and heart rate were monitored over 15 days, revealing a statistically significant positive correlation between core body temperature and cardiac performance, with an approximately 25% increase per °C. Molecular analyses of cardiac tissue revealed a sequential antioxidant response. An early upregulation of gpx4 suggests immediate mitochondrial protection against lipid peroxidation, while the subsequent induction of gpx1, prdx3, and prdx5 indicates a broader cytosolic defence. Furthermore, the marked decoupling between elevated gpx1 transcript levels and diminished Selenium-dependent glutathione peroxidase activity highlights a hitherto unrecognised post-transcriptional regulatory mechanism under acute thermal stress. Our findings suggest that T. bernacchii activates a sequential, organ-specific stress response to short-term warming, which may allow it to overcome episodic heatwaves.

With the exacerbation of global warming, the salinization of both land and water resource is becoming increasingly severe. As a widely distributed economic crustacean, investigating the impact mechanism of saline-alkaline environment on Chinese mitten crab (Eriocheir sinensis) holds significant importance. Behavioral, histological, and molecular regulatory mechanism are crucial for elucidating the pathological injury in organisms. The heart, being a core organ involved in lifespan regulation, plays a pivotal role in this context. In this study, we employed behavioral, cellular/ultrastructural morphological analysis, along with integrative omics approach, to uncover the pathological injury mechanism in the heart of E. sinensis under saline-alkaline stress. The present research demonstrated that saline-alkaline stress induced behavioral disorder and histological damage, including adipocyte infiltration and subcellular injury such as ruptured mitochondrial cristae, enlarged endoplasmic reticulum, and dilated Golgi apparatus. An integrative analysis of the top 10 KEGG and GSEA pathways revealed significant downregulation in "Glyoxylate and dicarboxylate metabolism", "Propanoate metabolism", and "Fatty acid degradation", all of which were associated with energy metabolism and cardiac function. These metabolic changes collectively contributed to cardiac damage in E. sinensis under saline-alkaline stress. This study, for the first time, elucidated the mechanism of heart damage in E. sinensis under saline-alkaline condition from multiple perspectives. It provides critical insights into the comprehensive damage mechanism of E. sinensis in such environment, offers a theoretical reference for developing the E. sinensis breeding industry under saline-alkaline condition, and contributes to understanding the impact of climate change on crustaceans. Moreover, the utilization of the high-throughput histopathological analysis tool CellProfiler can significantly enhance research into pathological damage in E. sinensis as well as in other crustacean species.

Microplastic pollution has emerged as a pervasive and persistent stressor in aquatic environments, raising urgent concerns for ecosystem integrity and food safety. Given the ecological and commercial importance of shrimp as both key benthic organisms and human food sources, this review systematically synthesizes and critically evaluates 94 studies (2016-2025) addressing the toxicity and bioaccumulation of microplastics in shrimp species. We identify mechanistic pathways linking particle characteristics (size, shape, polymer type, and surface functionalization) to biological responses at molecular, cellular, organ, and organism levels. Lethal and sublethal outcomes are strongly dependent on microplastic properties, inducing organ-specific injuries to the hepatopancreas, gills, muscle, gut, and gonads. Multi-omics and biochemical analyses reveal oxidative stress, immune dysfunction, apoptosis, metabolic disturbance, and neurotoxicity as core mechanistic cascades underlying growth inhibition, with potential links to reproductive impairment. Although most studies were laboratory-based, the convergence of evidence underscores that current exposure levels pose tangible ecological risks. These findings highlight shrimp as effective bioindicators for assessing microplastic pollution in aquatic systems. By bridging mechanistic evidence with ecological implications, this review provides a framework for risk assessment and informs management strategies to mitigate microplastic impacts on aquatic ecosystems and seafood safety.

Benzo[a]pyrene (B[a]P), a prominent persistent organic pollutant that is widespread in marine environment due to anthropogenic activities, poses considerable threats to marine ecosystem and public health. Although prior research has documented the adverse impacts of B[a]P on organisms and their response to relieve injury, there are relatively few studies on marine crustaceans that show commercial significance. In this study, we investigated the dose- and time-dependent effects of B[a]P on the lipid peroxidation and gene expression in the hepatopancreas and gill of Marsupenaeus japonicus. The results revealed that malondialdehyde contents in the hepatopancreas and gills of M. japonicus increased at 5 μg/L and 50 μg/L B[a]P exposure, indicating that higher B[a]P concentrations could induce lipid peroxidation. Exposure to 50 μg/L B[a]P resulted in the downregulated expression of several antimicrobial protein genes, including C-type lectins, i-type lysozyme, and stylicin. In contrast, B[a]P exposure significantly upregulated the gene expression of heat shock proteins and antioxidant enzymes. Moreover, correlation analysis suggested that malondialdehyde (MDA) content and gene expression levels in the hepatopancreas and gill of M. japonicus could serve as candidate biomarkers for B[a]P. Overall, this study provided basic insights into the effects of B[a]P on oxidative stress and gene expression in M. japonicus, enriched the understanding of molecular mechanisms in crustaceans responding to B[a]P stress, and identified candidate biomarkers for B[a]P.