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

High-fat diet (HFD) and Streptococcus agalactiae are common pathogenic factors affecting tilapia health, yet their combined effects and underlying mechanisms are not well understood. To address this, we conducted a comprehensive evaluation of the potential response mechanisms in tilapia subjected to both factors. Tilapia were fed normal (NC) or high-fat diet (HFD) for 90 days, then challenged with S. agalactiae. At 48 h post-infection, blood, liver, and spleen samples were collected for biochemical parameter analysis and gene expression profiling. The results indicated that the combined treatment upregulated the expression of peroxisome proliferator-activated receptor α (pparα) and fatty acid transport protein 1 (fatp1). Concurrently, it increased 3-hydroxy-3-methylglutaryl-CoA reductase (hmgcr) expression, while decreasing cholesterol 7α-hydroxylase (cyp7a1) expression compared to HFD alone. Antioxidant status analysis revealed that the combined treatment decreased glutathione (GSH) content, total antioxidant capacity (T-AOC), and mRNA levels of nuclear factor erythroid 2-related factor 2 (nrf2), NAD(P)H quinone dehydrogenase 1 (nqo1), and glutathione peroxidase 3 (gpx3). Intriguingly, while both individual stressors upregulated inflammatory and immune-related genes, their combination suppressed interleukin-1β (il-1β), il-8, and immunoglobulin M (igm) expression compared to infection alone. The apoptotic response triggered by S. agalactiae infection, characterized by elevated caspase-3 (cas3), cas9, and cytochrome c (cytc), was inhibited in the liver of combined treatment group. Moreover, all experimental groups showed elevated expression of endoplasmic reticulum stress-related genes: inositol-requiring enzyme 1 (ire1), eukaryotic translation initiation factor 2 alpha kinase 3 (eif2ak3), activating transcription factor 6 (atf6), and binding immunoglobulin protein (bip). These findings collectively demonstrated that HFD exacerbated the pathogenic effects of S. agalactiae through multiple mechanisms, including metabolic dysregulation, oxidative stress potentiation, and complex immunomodulation. Furthermore, the Nrf2 and NF-kB signaling pathways may be implicated in mediating these adverse effects.

Ongoing global climate change and anthropogenic activities are increasingly subjecting aquatic animals to heat and hypoxia stress. These environmental perturbations can profoundly impact mitochondrial function and energy metabolism. The current study aimed to delineate the adaptive mechanisms of mitochondrial dynamics and energy metabolism in the blunt snout bream (Megalobrama amblycephala) under three experimental conditions: heat stress (HT group, 35 °C of temperature), hypoxia stress (LO group, 2 mg/L of dissolved oxygen), and combined heat plus hypoxia stress (HL group, 35 °C and 2 mg/L). The results demonstrated that heat and/or hypoxia stresses damaged mitochondrial structure and disrupted fusion-fission balance. The activities of key TCA cycle enzymes (e.g. SDH, CS) were significantly decreased. Conversely, energy metabolism was regulated through an increased AMP/ATP ratio and activation of AMPKα1/AMPKα2 proteins. The expression of glycolytic enzymes (PK, PFK, HK and LDH) was up-regulated. However, heat and/or hypoxia stresses resulted in severe consumption of serum glucose and liver glycogen, with the most pronounced consumption in the HL group. Other saccharides such as mannose and lactose were also significantly reduced in HT and HL groups. The decomposition and metabolism of amino acids was an important auxiliary mechanism. Regarding lipid metabolism, the expression of lipolysis and lipogenesis related genes was down-regulated, while glycerophospholipids accumulation contributed to maintaining membrane integrity. These findings benefit the understanding of environmental adaptive characteristics in aquatic animals and provide effective strategies for aquaculture management.

Styrene is an environmental toxicant metabolized by cytochrome P450 2E1 (CYP2E1) to styrene oxide, a reactive intermediate product linked to oxidative stress. While the role of CYP2E1 in xenobiotic metabolism is well established, the influence of subcellular enzyme localization on styrene-induced toxicity remains unclear. This study used transgenic Caenorhabditis elegans (C. elegans) strains expressing CYP2E1 in different compartments, mitochondrial-derived (mtCYP2E1) and endoplasmic reticulum-derived (erCYP2E1), to investigate the impact of CYP2E1-mediated styrene metabolism on survival and oxidative stress. CYP2E1 containing C. elegans strains were also compared to a wildtype strain (N2) lacking CYP2E1. Styrene exposure significantly decreased survival across all strains. Antioxidant rescue assays revealed that Trolox and N-acetyl cysteine (NAC) improved survival in the N2 and erCYP2E1 C. elegans strains but not in mtCYP2E1, indicating a distinct oxidative stress mechanism in mitochondrial CYP2E1 metabolism. Fluorescent microscopy confirmed that ROS levels increased with styrene exposure, particularly in mtCYP2E1 C. elegans, where ROS levels were up to two-fold higher than in other strains. GC-MS analysis detected elevated styrene glycol production in styrene-exposed mtCYP2E1 C. elegans relative to N2 and erCYP2E1 strains. Given styrene oxide is a known cytotoxic intermediate, its accumulation in the mtCYP2E1 strain likely contributes to the observed oxidative stress and decreased survival. These findings suggest that CYP2E1 subcellular localization influences styrene metabolism and toxicity, with mitochondrial CYP2E1 potentially promoting higher oxidative stress and reduced detoxification efficiency. A better understanding of these mechanisms could provide insight into xenobiotic metabolism, environmental toxicology, and disease pathogenesis associated with CYP2E1-mediated oxidative stress.

Climate change and pollution represent critical stressors for marine ecosystems, particularly for calcifying organisms such as the sea urchin Paracentrotus lividus. This study examines the combined effects of ocean acidification (OA), ocean warming (OW), and microplastics (MP) loaded with chlorpyrifos (CPF), a broad-spectrum organophosphate insecticide, on sea urchin larvae, evaluating growth and molecular endpoints. Experimental treatments simulated future ocean conditions predicted for 2100, exposing larvae to varying temperature and pH levels, alongside CPF-contaminated MP. RNA sequencing (RNA-seq) was utilized to assess gene expression changes, revealing significant transcriptional shifts in metabolic, cellular, and developmental pathways. Morphological responses showed reduced larval growth, exacerbated under OA and OW conditions. Molecular analyses identified key upregulated pathways associated with stress response, including nitrogen metabolism and extracellular matrix remodelling, while downregulated genes involved DNA stability, cell cycle regulation, and enzymatic activities. These findings suggest a dual compensatory and deleterious response to combined stressors. Notably, temperature acted as a modulator of stressor effects, amplifying oxidative stress and metabolic costs at higher temperatures. Potential biomarkers, such as genes involved in actin regulation and embryonic development, were identified, offering possible tools for early detection of environmental stress. This study highlights the compounded impacts of anthropogenic and climate-induced stressors on marine invertebrates, emphasizing the need for integrative molecular approaches in ecotoxicology. Our findings contribute to the understanding of organismal adaptation and vulnerability in the face of global climate change and pollution, informing conservation strategies for marine ecosystems.