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

High molecular weight proteins are present abundantly in viperid venoms. The amino acid sequence can be highly variable, contributing to the structure and function diversity of snake venom protein. However, this variability remains poorly understood in many species. The study investigated the venom protein variability in a distinct clade of Asian pit vipers (Trimeresurus species complex) through comparative proteomics, applying gel electrophoresis (SDS-PAGE), liquid chromatography-tandem mass spectrometry (LCMS/MS), and bioinformatic approaches. The proteomes revealed a number of conserved protein families, within each are variably expressed protein paralogs that are unrelated to the snake phylogeny and geographic origin. The expression levels of two major enzymes, i.e., snake venom serine proteinase and metalloproteinase, correlate weakly with procoagulant and hemorrhagic activities, implying co-expression of other functionally versatile toxins in the venom. The phospholipase A₂ (PLA₂) abundance correlates strongly with its enzymatic activity, and a unique phenotype was discovered in two species expressing extremely little PLA₂. The commercial mono-specific antivenom effectively neutralized the venoms' procoagulant and hemorrhagic effects but failed to inhibit the PLA₂ activities. Instead, the PLA₂ activities of all venoms were effectively inhibited by the small molecule inhibitor varespladib, suggesting its potential to be repurposed as a highly potent adjuvant therapeutic in snakebite envenoming.

Heat waves, are a major concern related to climate change, and are projected to increase in frequency and severity. This temperature rise causes thermal stratification, exposing surface-dwelling organisms to higher levels of ultraviolet radiation (UVR). This study aims to understand how the toxic bloom-forming cyanobacterium Microcystis aeruginosa adapts to changing climatic conditions. The effects of increased temperature and UVR were evaluated in terms of cell abundance, reactive oxygen and nitrogen species (ROS/RNS), the antioxidant activity of catalase (CAT), superoxide dismutase (SOD), glutathione S transferase (GST), fatty acid (FA) content, and lipid damage. Negative UVR effects on biomass, lipid damage, and polyunsaturated fatty acids (PUFAs) were more pronounced at 26 °C compared to 29 °C. However, antioxidant responses were higher at 29 °C. The relative abundance of ω6 FAs was less affected by UVA, while ω3 FAs were highly sensitive at 29 °C but unsaturated fatty acids (UFA) did not experience peroxidation. The differential response in FA to high temperature and UVR results in differences in lipid damage and antioxidants. Changes in membrane FA may suggest an adaptation strategy at high UVR conditions. The exposure to environmental changes can alter membrane fluidity, affecting cell physiology. Thus, to survive UVR exposure, M. aeruginosa maintains a balance between damage and stress adaptation, increasing the protection of selected PUFAs at high temperatures, allowing them to effectively cope with the harmful effects of elevated temperature and UVR.

Per and polyfluoroalkyl substances (PFAS) are anthropogenic chemicals extensively used in consumer products. Perfluorobutane sulfonate (PFBS), a short-chain PFAS, has been introduced as an alternative to long-chain PFAS, but limited studies have investigated its reproductive toxicity in fish. In this study, adult zebrafish were exposed to PFBS at concentrations of 0.14, 1.4, and 14 μM for 28 days. PFBS accumulation in male and female gonads was confirmed by specific mass spectrum peaks detected in exposed samples. PFBS exposure at 14 μM significantly reduced egg production and hatching rates. The gonadosomatic index (GSI) was decreased by 73 % in males and 50 % in females compared to the control. PFBS impaired antioxidant enzyme activity, with superoxide dismutase (SOD) 4.73 U/mg protein in testes and 3.46 U/mg protein in ovaries, leading to elevated lipid peroxidation and nitric oxide levels in males (0.053 μmol/mg/ml and 5.65 μM) and females (0.047 μmol/mg/ml and 4.01 μM), respectively. PFBS exposure induced endocrine disruption through the hypothalamic-pituitary-gonadal-liver (HPGL) axis, showing increased estrogen (50 pg/g) in males and testosterone (181.6 pg/g) in females. Gene expression analysis revealed significant alteration in the HPGL axis, including cyp19b, er2b, fshb, lhb, 17βhsd, lhr, cyp19a, and vtg, indicating PFBS influence on sex hormone synthesis. Histopathological analysis of PFBS exposure groups revealed a reduction of spermatozoa in the testes and late vitellogenic oocytes in the ovaries. Overall, the result of the present study indicates that PFBS exposure induces oxidative stress, disrupts hormone synthesis, dysregulates HPGL axis gene expression, and causes reproductive toxicity in both male and female zebrafish.

Olanzapine (OLZ) is widely used in the treatment of schizophrenia, and its metabolic side effects have garnered significant attention in recent years. Despite this, the specific side effects of OLZ and the underlying mechanisms remain inadequately understood. To address this gap, zebrafish (Danio rerio) were exposed to OLZ at concentrations of 35.5, 177.5, and 355.5 μg/L. The results indicated that exposure to OLZ significantly increased body weight, total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG). Histological analysis revealed notable lipid accumulation in the liver. Furthermore, lipid synthesis genes, including sterol regulatory element binding protein (srebp), acetyl CoA carboxylase (acc), and fatty acid synthesis gene (fas), were up-regulated. In contrast, genes related to lipid decomposition, such as lipoprotein lipase (lpl), hormone-sensitive triglyceride lipase (hsl), and carnitine palmitoyltransferase 1b (cpt1b), were down-regulated. Subsequent analysis of zebrafish behavior showed reduced motor activity, sociability, and anxiety-like behavior in OLZ-exposed zebrafish, consistent with the results of neurotransmitter related gene expression. Following OLZ treatment, the expression of tryptophan hydroxylase (tph), tyrosine hydroxylase (th), dopamine transporter (dat), glutaminase (glsa), and glutamic acid decarboxylase 1b (gad1b) was upregulated. Additionally, the diversity of intestinal flora decreased after OLZ exposure, and the structure of the intestinal microbiota changed significantly compared to the control group. At the genus level, the abundance of Plesiomonas was upregulated, while the abundances of Bacillus and Cetobacterium were downregulated in the OLZ-exposed group. Furthermore, the results of the correlation analysis indicated that lipid metabolism and behavioral changes were closely associated with the microbiota. This study clarified the side effects of OLZ, and also provided a basis for the reasonable discharge concentration of OLZ in water and clinical drug use.

The intricate interaction among host, pathogen, and environment significantly influences aquatic health, yet the influence of hypoxic stress combined with bacterial infection on host response is understudied. Circular RNAs with stable closed-loop structures have emerged as important regulators in immunity, yet remain ill-defined in fish. In this study, we systematically explored the circRNA response in yellow catfish subjected to combined hypoxia-bacterial infection (HB) stress. Following HB stress, H&E and TUNEL staining identified heightened hepatocyte apoptosis, intracellular vacuolation, and inflammatory tissue damage. RT-qPCR elucidated that differentially expressed genes stimulated by HB synergistically enhanced apoptosis and inflammatory responses. Importantly, we systematically evaluated differentially expressed circRNAs (DEcirs) in yellow catfish under hypoxia with and without Aeromonas veronii infection and identified a novel HB-specific DEcir, designated as circArid4b, whose parental gene Arid4b is highly associated with apoptosis. Experiments confirmed the circular structure of circArid4b and revealed that under HB stimulation, specific knockdown of circArid4b inhibited the expression of Arid4b, while concurrent alterations in multiple apoptosis- and inflammation-related genes synergistically indicated the promotion of apoptotic and inflammatory pathways. Notably, the downregulation of circArid4b expression significantly reduced the susceptibility to bacterial infection in yellow catfish during hypoxia. These results suggest that HB-induced suppression of circArid4b promotes cell apoptosis and inflammation by inhibiting its parental gene and thereby facilitating resistance to bacterial infection during hypoxia. Our study enriches the understanding of fish circRNA mechanisms and offers novel preventive and control strategies for bacterial infections in fish under hypoxic environments.

The compound m-Cresol, also referred to as 3-methylphenol,acts as a precursor in the creation of pesticides and plasticizers. This research has conducted a thorough evaluation of the toxic effects of m-cresol on the cardiac development of juvenile zebrafish, from 6 to 72 hpf. The study's results reveal that higher concentrations of m-Cresol, compared to lower ones, result in more severe heart abnormalities in zebrafish larvae. The pericardial edema becomes more pronounced, the atrial-ventricular distance gradually increases, and the absorption of nutrients is delayed. Furthermore, experimental studies have shown that m-cresol can cause excessive oxidative stress and apoptosis in juvenile zebrafish during their early developmental stages. Additionally, our transcriptomic analysis indicates that m-Cresol exposure may cause cardiac developmental toxicity in zebrafish larvae by affecting the expression levels of genes (Myosin VIIa:my17,Myosin XIV:my14, Alpha-cardiac actin:actc1a,and Non-muscular myosin heavy chain 9 A:myh9a) involved in the ion channel signaling pathway and cardiomyocyte development. These findings collectively demonstrate the developmental toxicity of m-Cresol to the hearts of larval zebrafish.

It has been reported that enrofloxacin (ENR) disrupts metabolic pathway of steroid in female crucian carp, promoting testosterone (T) synthesis through stimulating expression of luteinizing hormone (LH) and inhibiting conversion of T to estradiol (E₂) through repressing aromatase A expression. To further learn effect of ENR on steroid metabolism in fish, this work investigated effect of ENR on central E₂ synthesis and the involved mechanisms in female crucian carp through evaluating contents of T and E₂ in blood and brain, expression of secretogranin 2a (scg2a), gonadotrophin 2 β (gth 2β, namely LH) and aromatase B (cyp19a1b) genes in brain, and activation of PI3K/Akt pathway in brain of ENR exposed female crucian carp. Results revealed that ENR promoted steroid metabolism in brain of female crucian carp, stimulated synthesis of T synthesis but inhibited conversion of T to E₂ through promoting expression of scg2a and gth 2β but repressing expression of cyp19a1b, PI3K/Akt signaling pathway participated in regulating the biological process.

Studies showed that contaminants adhered to the surface of nano-polystyrene microplastics (NPs) have a toxicological effect. Juveniles tilapia were dispersed into four groups: the control group A, 75 nm NPs exposed group B, 5 ng·L^-1 2,2',4,4',5,5'-hexabromodiphenyl ether group C (BDE₁₅₃), and 5 ng·L^-1 BDE₁₅₃ + 75 nm MPs group D, and acutely exposed for 2, 4 and 8 days. The hepatic histopathological change, enzymatic activities, transcriptomics, and proteomics, have been performed in tilapia. The results showed that the enzymatic activities of anti-oxidative (ROS, SOD, EROD), energy (ATP), lipid metabolism (TC, TG, FAS, LPL, ACC), pro-inflammatory (TNFα, IL-1β) and apoptosis (caspase 3) significantly increased at 2 d in BDE₁₅₃ and the combined group and together in BDE₁₅₃ group at 8 d. Histological slice showed displaced nucleus by BDE₁₅₃ exposure and vacuoles appeared in the combined groups. KEGG results revealed that pathways associated with endocytosis, protein processing in endoplasmic reticulum and regulation of actin cytoskeleton were significantly enriched. The selected genes associated with neurocentral development (ganab, diaph3/baiap2a/ddost decreased and increased), lipid metabolism (ldlrap1a decreased, stt3b increased), energy (agap2 decreased, uggt1 increased) were affected under co-exposure, and fibronectin significantly increased via proteome. Our study indicated that endocytosis, protein processing in endoplasmic reticulum, regulation of actin cytoskeleton were affected in tilapia liver under NPs and BDE₁₅₃ co-exposure.

Spodoptera frugiperda is a significant agricultural pest, severely impacting the yield and quality of grain. Chitin is the momentous component of exoskeletons, which has a significant impact on the growth and development of insects. Our previous study found that exposure to lufenuron can reduce the expression of chitinase gene (SfCHT5) and increase the expression of chitin synthase gene (SfCHSB), two key genes for chitin synthesis in S. frugiperda. However, the post-transcriptional regulatory mechanisms of these key genes in S. frugiperda remain unclear. With miRNA as the entry point, target site prediction, dual luciferase reporter assays, and mimics/inhibitors injection were used to explore the post-transcriptional regulatory mechanism of SfCHSB and SfCHT5. The combined results confirm that miR-10482-5p targets SfCHT5 and regulates its expression, while miR-9a targets and regulates the expression of both SfCHT5 and SfCHSB. Additionally, injection of miR-10482-5p and miR-9a mimic significantly reduced the mortality rates of S. frugiperda treated with lufenuron, increased pupation rate, and emergence rate. These findings underscore the critical regulatory role of miR-10482-5p and miR-9a in modulating the expression of key genes involved in chitin synthesis, thereby enhancing the tolerance of S. frugiperda to lufenuron and influencing its growth and development. In summary, this study preliminarily elucidates the post-transcriptional regulatory mechanisms of miRNA-mediated SfCHSB and SfCHT5 expression.

Daphnia's antipredator responses are regulated largely by the nervous system, making these responses particularly susceptible to compounds that impact neurodevelopmental or neurofunctional processes. This study aimed to determine the molecular pathways involved in modulating the effects of scopolamine on inducible antipredation responses triggered by fish kairomones. We used two clones showing two contrasting responses. The positive phototactic clone 85 responds strongly to fish kairomones showing a marked negative phototactism and higher developmental rates. Consistently, the negative phototactic clone F shows the opposite behavior to the same stimuli. Adults of both clones were exposed to fish kairomones, scopolamine alone and a mixture of both. Scopolamine is a muscarine antagonist able to mimic fish kairomones inducible behavioral responses in both clones, while affecting differently morphological and life-history traits. Whole transcriptomic Illumina analyses indicated a greater number of de-regulated genes of the fish kairomone sensitive clone 85 (1650) compared to the F one (1138), which were grouped in four clusters (two per clone). The mixture of scopolamine and fish kairomone treatments on gene transcription was additive in both clones, indicating similar modes of action. Most enriched metabolic routes were related with neurological pathways and regulation of cell proliferation/differentiation. Our results indicate that fish kairomones and scopolamine deregulate not only neurological signaling pathways but also cell differentiation and proliferation pathways, which are linked to the observed behavioral responses as well as the developmental, morphological, and reproductive effects.