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

{"title":"The effects of microplastics exposure on quail's hypothalamus: Neurotransmission disturbance, cytokine imbalance and ROS/TGF-β/Akt/FoxO3a signaling disruption","authors":"Qingyu Zhang ,&nbsp;Siyuan Zheng ,&nbsp;Xiaoqing Pei ,&nbsp;Yuxin Zhang ,&nbsp;Gang Wang ,&nbsp;Hongfeng Zhao","doi":"10.1016/j.cbpc.2024.110054","DOIUrl":"10.1016/j.cbpc.2024.110054","url":null,"abstract":"<div><div>Microplastics (MPs) have become a major focus of environmental toxicology, raising concerns about their potential adverse effects on animal organs and body systems. As these tiny particles infiltrate ecosystems, they may pose risks to the health of organisms across diverse species. In this study, we attempted to examine the neurotoxic effects of MPs exposure on avian hypothalamus by using an animal model-Japanese quail (<em>Coturnix japonica</em>). The quails of 7-day-old were exposed to 0.02 mg/kg, 0.4 mg/kg and 8 mg/kg polystyrene microplastic (PS-MPs) of environmental relevance for 35 days. The results showed PS-MPs exposure did damages to hypothalamic structure characterized by neuron malformation, irregular arrangement and cellular vacuolation after 5-week exposure. PS-MPs exposure also induced Nissl body reduction and dissolution in the hypothalamus. Moreover, the decrease of acetylcholinesterase (AchE) activity and increasing acetylcholine (Ach) indicated that PS-MPs exposure caused hypothalamic neurotransmission disturbance. PS-MPs exposure also led to neuroinflammation by disrupting the balance between proinflammatory and anti-inflammatory cytokines. Moreover, increasing reactive oxygen species (ROS) and malondialdehyde (MDA) generation with reducing antioxidants indicated PS-MPs led to hypothalamic oxidative stress. Additionally, RNA-Seq analysis found that both transforming growth factor-β (TGF-β) signaling and forkhead box O (FoxO) signaling were disturbed in the hypothalamus by PS-MPs exposure. Especially, the increasing ROS led to TGF-β activation and then induced hypothalamic inflammation by nuclear factor κB (NF-κB) activation. The present study concluded that oxidative stress might be an important mechanistic signaling involved in MPs neurotoxicology.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"287 ","pages":"Article 110054"},"PeriodicalIF":3.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute and multigenerational effects of short-chain chlorinated paraffins on the harpacticoid copepod Tigriopus japonicus","authors":"Jihyun Lee ,&nbsp;Seong Duk Do ,&nbsp;Jae-Sung Rhee","doi":"10.1016/j.cbpc.2024.110055","DOIUrl":"10.1016/j.cbpc.2024.110055","url":null,"abstract":"<div><div>Although the measurement of short-chain chlorinated paraffins (SCCPs) in aquatic ecosystems has increased, limited information is available on their toxic effects on aquatic animals. To evaluate the harmful effects of SCCPs, we assessed their acute impact on 24-h survival and biochemical parameters, as well as their chronic effects on growth and reproduction over three generations in the harpacticoid copepod <em>Tigriopus japonicus</em>. Dose-dependent increases in mortality were observed, with an LC50 value of 74.6 μg L⁻¹ for 24 h. Acute exposure to the LC10 value for 24 h significantly reduced feeding behavior, accompanied by a notable decrease in acetylcholinesterase enzymatic activity. Simultaneously, the intracellular levels of reactive oxygen species increased, along with elevated malondialdehyde contents. Glutathione level was increased by the LC10 value of SCCPs with the induction of enzymatic activities of antioxidant defense components, including glutathione <em>S</em>-transferase, catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. When <em>T. japonicus</em> was continuously exposed to 1/10 of the NOEC and NOEC values for 12 days across three generations (F0–F2), growth retardation was observed in the F2 generation, with delay in the developmental periods from nauplius to adult. Although the total number of nauplii per brood was not significantly altered across generations, a significant delay in the onset of reproduction was observed in the F2 generation. Our findings suggest that even sublethal concentrations of SCCPs can negatively affect the health of copepod populations with consistent exposure.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"287 ","pages":"Article 110055"},"PeriodicalIF":3.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the chronic toxicity of climbazole to Daphnia magna: Physiological, biochemical, molecular, and reproductive perspectives","authors":"Donglin Yuan ,&nbsp;Bangjun Zhang","doi":"10.1016/j.cbpc.2024.110061","DOIUrl":"10.1016/j.cbpc.2024.110061","url":null,"abstract":"<div><div>The widespread use of climbazole (CBZ) has led to its increased presence in aquatic environments, potentially threatening freshwater ecosystems. However, evidence regarding the harmful effects of CBZ on aquatic organisms remains limited. In this study, <em>Daphnia magna</em> was exposed to CBZ at concentrations of 0, 0.2, 20, and 200 μg/L for 21 days to evaluate its chronic toxicity through assessment of life-history traits, physiological parameters, biochemical analyses, and gene expression. The results indicated that CBZ exposure delayed the days to the first brood, reduced the frequency of molting per adult, decreased the offspring number at first brood, diminished the body length, and decreased both the total number of broods per female and the total number of offspring per female. Additionally, CBZ inhibited the swimming speed, filtration rate, and ingestion rate. Moreover, CBZ altered the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), while increasing malondialdehyde (MDA) levels. Gene expression analysis revealed varied responses in mRNA levels related to metabolic detoxification (<em>cyp360a8</em>, <em>gst</em>, and <em>p</em>-<em>gp</em>), digestive enzymes (<em>α</em>-<em>amylase</em>, <em>α</em>-<em>esterase</em>, and <em>trypsin</em>), energy (<em>ak</em>), oxygen transport (<em>dhb</em>), and reproduction (<em>nvd</em>, <em>cyp314</em>, <em>ecr</em>, <em>vtg</em>, and <em>jhe</em>) following CBZ exposure. These results indicate that the presence of CBZ in aquatic environments can induce toxicity by altering energy acquisition, supply, and metabolism; impairing metabolic detoxification pathways; eliciting oxidative stress; and causing reproductive toxicity in <em>D. magna</em>.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"287 ","pages":"Article 110061"},"PeriodicalIF":3.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated temperature increases the susceptibility of D. magna to environmental mixtures of carbamazepine, tramadol and citalopram","authors":"András Ács ,&nbsp;János Schmidt ,&nbsp;Zoltán Németh ,&nbsp;István Fodor ,&nbsp;Anna Farkas","doi":"10.1016/j.cbpc.2024.110052","DOIUrl":"10.1016/j.cbpc.2024.110052","url":null,"abstract":"<div><div>The joint risks assessment of thermal stress and rising loads of pharmaceuticals (PhACs) in surface waters is a relevant topic in aquatic ecotoxicology. This study investigated the relevance of increased water temperature to alter the acute toxicity of environmentally relevant carbamazepine (CBZ), citalopram (CIT) and tramadol (TRA) concentrations as mixtures (ECs) and delayed outcomes in <em>Daphnia magna</em>. Responses of detoxification and antioxidant pathways in premature daphnids post an acute 24 h (pulsed) exposure to the PhACs mixtures and delayed responses as the reproductive output over 14 days recovery were investigated under 21- and 26 °C incubation. Biphasic modulation in glutathione S-transferase (GST) activity and significant inhibition of superoxide dismutase (SOD) activity were observed in both thermal regimes with significant shift in effective thresholds from 10-fold ECs at 21 °C to ECs at 26 °C incubation. Significant induction in catalase (CAT) activity and oxidative stress development were recorded at elevated temperatures from the 10-fold ECs dose onward. Pulsed exposures at 26 °C also led to significant decrease in the reproduction of daphnids above the 10-fold ECs of PhACs. The Integrated Biomarker Response scoring (IBRv2) approach outlined a 1.8-fold increase in alterations of daphnids exposed to 100-fold ECs of PhACs at 26 °C.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"287 ","pages":"Article 110052"},"PeriodicalIF":3.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embryonal exposure to 4-methylbenzylidene camphor induces reproduction impairment in adult zebrafish (Danio rerio)","authors":"Ved Prakash ,&nbsp;Mohammad Imran Ansari ,&nbsp;Shwetha Singh Chauhan ,&nbsp;Ramakrishnan Parthasarathi ,&nbsp;Sadasivam Anbumani","doi":"10.1016/j.cbpc.2024.110051","DOIUrl":"10.1016/j.cbpc.2024.110051","url":null,"abstract":"<div><div>This study investigated how early exposure to xenobiotics can lead to disease in adulthood, which is challenging for toxicologists. We employed a ‘cradle to grave’ approach using zebrafish (<em>Danio rerio</em>) embryos exposed to 4-methylbenzylidene camphor (4-MBC), a commonly used organic UV filter. Molecular docking and simulation studies confirmed the predictive toxicity and stable interaction of 4-MBC with androgen and estrogen receptors, with binding energies of −9.28 and −9.01 kcal/mol, respectively. Exposure to 4-MBC at 5, 50, and 500 μg/L concentrations resulted in significantly altered transcriptional and translational responses of <em>ar</em>, <em>esr1</em>, and <em>vtg1</em> genes in embryos at 120 h post-fertilization (hpf). The exposure induced a non-monotonic dose-response pattern (NMDR), a characteristic feature of endocrine-disrupting chemicals. Additionally, a significant decrease in fertilization was observed in adults. Although fecundity was not affected in inter- and intra-breeding performances, developmental deformities were observed in F1 progenies with impaired survival at 10 days post-fertilization. The findings of this study show that embryonic exposure to 4-MBC is likely to induce reproductive and transgenerational toxicity in <em>D. rerio</em> and exhibit endocrine disruption in aquatic non-target organisms. This work is the first to elucidate the low-level long-term effects of 4-MBC from the embryonic stage to adulthood.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"287 ","pages":"Article 110051"},"PeriodicalIF":3.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single and combined effects of phenanthrene and cadmium on oxidative stress and detoxification related biomarkers in clams (Meretrix meretrix)","authors":"Yuanyuan Jing,&nbsp;Tianwen Zhang,&nbsp;Fanguang Hu,&nbsp;Guangbin Liu,&nbsp;Ming Sun","doi":"10.1016/j.cbpc.2024.110050","DOIUrl":"10.1016/j.cbpc.2024.110050","url":null,"abstract":"<div><div>Biomarkers concerning antioxidant reactions and detoxification metabolics were evaluated in <em>Meretrix meretrix</em> exposed to cadmium (Cd, 10 μg/L) and phenanthrene (PHE, 100 μg/L) individually and in combination (10 μg/L Cd + 100 μg/L PHE) for 7 days. The accumulation of Cd and PHE measured in the digestive gland, gill, mantle, and axe foot of the clam showed significant increase in combination treatment and it was higher than the single Cd or single PHE treatment. The activities of oxidative stress-related enzymes, the expression of <em>Cu</em>/<em>Zn SOD</em>, and the content of MDA increased after Cd and PHE exposure in the digestive gland and gill at most cases. In the digestive gland, <em>CAT</em> gene expression was significantly induced in Cd-single group and significantly inhibited in PHE-single group and Cd-PHE mixed group at both day 3 and day 7; in the gill, <em>CAT</em> gene expression was significantly inhibited in all groups at day 3 and except for Cd-single group at day 7. <em>MT</em> expression was significantly induced in Cd-single and Cd-PHE mixed groups at day 7, while <em>hsp70</em> expression was significantly inhibited in PHE-single and Cd-PHE mixed groups at day 7. The results indicated that SOD, CAT, GST, MDA, <em>Cu/Zn SOD</em>, <em>CAT</em>, <em>MT</em> and <em>hsp70</em> were sensitive to cadmium and PHE in a water environment, and can be used as indicators of marine heavy metal pollution.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"287 ","pages":"Article 110050"},"PeriodicalIF":3.9,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative biochemical characterization of pufferfish saxitoxin and tetrodotoxin-binding protein (PSTBP) homologs in the plasma from four Takifugu species: Conservation of heat-stable PSTBP orthologs having three and two tandemly repeated lipocalin domains in genus Takifugu","authors":"Yafei Zhang ,&nbsp;Mikinori Ueno ,&nbsp;Ryohei Tatsuno ,&nbsp;Tomohiro Takatani ,&nbsp;Yohei Shimasaki ,&nbsp;Kazunari Arima ,&nbsp;Mary Grace Sedanza ,&nbsp;Kenichi Yamaguchi ,&nbsp;Yuji Oshima ,&nbsp;Osamu Arakawa","doi":"10.1016/j.cbpc.2024.110049","DOIUrl":"10.1016/j.cbpc.2024.110049","url":null,"abstract":"<div><div>To study the relationship between domain characteristics of pufferfish saxitoxin and tetrodotoxin binding protein (PSTBP) proteoforms and their thermal stability, a comparative biochemical characterization of PSTBPs from the plasma of four <em>Takifugu</em> species (<em>T. flavipterus</em>, <em>T. pardalis</em>, <em>T. alboplumbeus</em> and <em>T. rubripes</em>) was conducted by Western blot analysis. The heat-tolerance tetrodotoxin (TTX)-binding ability of PSTBP proteoforms in <em>T. rubripes</em> plasma was verified by ultrafiltration and liquid chromatography tandem mass spectrometry (LC-MS/MS). These results suggest that the heat-stable PSTBP proteoforms, composed of three and two tandemly repeated lipocalin domains, are genetically conserved and ubiquitous in the genus <em>Takifugu</em>. This study builds on our knowledge of the structural and functional properties of PSTBP proteoforms, which is vital for understanding how toxins are transmitted and accumulate in organisms and is essential for evaluating the potential risks of toxins in seafood.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"287 ","pages":"Article 110049"},"PeriodicalIF":3.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability and expression patterns of housekeeping genes in Mediterranean mussels (Mytilus galloprovincialis) under field investigations","authors":"Letizia Iuffrida ,&nbsp;Rajapaksha Haddokara Gedara Rasika Wathsala ,&nbsp;Margherita Musella ,&nbsp;Giorgia Palladino ,&nbsp;Marco Candela ,&nbsp;Silvia Franzellitti","doi":"10.1016/j.cbpc.2024.110047","DOIUrl":"10.1016/j.cbpc.2024.110047","url":null,"abstract":"<div><div>The use of marine mussels as biological models encompasses a broad range of research fields, in which the application of RNA analyses disclosed novel biomarkers of environmental stress and investigated biochemical mechanisms of action. Quantitative real-time PCR (qPCR) is the gold standard for these studies, and despite its wide use and available protocols, it may be affected by technical flaws requiring reference gene data normalization. In this study, stability of housekeeping genes commonly employed as reference genes in qPCR analyses with <em>Mytilus galloprovincialis</em> was explored under field conditions. Mussels were collected from farms in the Northwestern Adriatic Sea. The sampling strategy considered latitudinal gradients of environmental parameters (proxied by location), gender, and their interactions with seasonality. Analyses of gene stability were performed using different algorithms. BestKeeper and geNorm agreed that combination of the ribosomal genes 18S ribosomal RNA (18S) and 28S ribosomal RNA (<em>28S)</em> was the best normalization strategy in the conditions tested, which agrees with available evidence. NormFinder provided different normalization strategies, involving combinations of tubulin (<em>TUB)/28S</em> (Gender/Season effect) or <em>TUB/</em>helicase <em>(HEL)</em> (Location/Season effect). Since NormFinder considers data grouping and computes both intra- and inter-group stability variations, it should work better with complex experimental designs and dataset structuring. Under the selected normalization strategies, expressions of the variable housekeeping genes actin (<em>ACT)</em> and elongation factor-1<em>α</em> (<em>EF1)</em> correlated with seasonal and latitudinal changes of abiotic environmental factors and mussel physiological status. Results point to consider <em>ACT</em> and <em>EF1</em> expressions as molecular biomarkers of mussel general physiological status in field studies.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"287 ","pages":"Article 110047"},"PeriodicalIF":3.9,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of 5α-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryos","authors":"Hyunki Cho ,&nbsp;Indong Jun ,&nbsp;Karim Md Adnan ,&nbsp;Chang Gyun Park ,&nbsp;Sang-Ah Lee ,&nbsp;Juyong Yoon ,&nbsp;Chang Seon Ryu ,&nbsp;Young Jun Kim","doi":"10.1016/j.cbpc.2024.110048","DOIUrl":"10.1016/j.cbpc.2024.110048","url":null,"abstract":"<div><div>Steroid 5α-reductase (SRD5A) is a crucial enzyme involved in steroid metabolism, primarily converting testosterone to dihydrotestosterone (DHT). Dutasteride, an inhibitor of SRD5A types 1 and 2, is widely used for treating benign prostatic hyperplasia. An adverse outcome pathway (AOP) has been documented wherein SRD5A inhibition decreases DHT synthesis, leading to reduced levels of 17β-estradiol (E2) and vitellogenin (VTG), subsequently impairing fecundity in fish (AOP 289). However, the molecular and cellular mechanisms underlying these effects remain poorly understood. In this study, we assessed the impact of SRD5A inhibition on zebrafish embryos <em>(Danio rerio)</em>. Exposure to dutasteride resulted in decreased DHT, E2, and VTG levels, showing a positive correlation. Dutasteride also downregulated the expression of reproduction-related <em>genes (srd5a2, cyp19a1, esr1, esr2a, esr2b,</em> and <em>vtg</em>), with interrelated reductions observed across these levels. Docking studies suggested that dutasteride's effects may operate independently of androgen receptor (AR) and estrogen receptor (ER) interactions. Furthermore, co-exposure of dutasteride (0.5 or 2 μM) with 0.5 μM DHT revealed gene expression levels comparable to the control group. These findings underscore DHT's pivotal role in modulating estrogenic function and the interplay between estrogenic and androgenic responses in vertebrates. Our proposed AOP model offers insights into mechanistic gaps, thereby enhancing current understanding and bridging knowledge disparities.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"287 ","pages":"Article 110048"},"PeriodicalIF":3.9,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluoxetine antagonizes the acute response of LPS: Blocks K2P channels","authors":"Elizabeth R. Elliott,&nbsp;Robin L. Cooper","doi":"10.1016/j.cbpc.2024.110045","DOIUrl":"10.1016/j.cbpc.2024.110045","url":null,"abstract":"<div><div>The channels responsible for maintaining resting membrane potential are known as K2P (two-P-domain K⁺ subunit) channels, a subset of which are known to be blocked by Fluoxetine. In this experiment, the compound's effects on the membrane potential were examined on muscles in larval <em>Drosophila</em> overexpressing a subtype of K2P channel (known in <em>Drosophila</em> as dORKA1 or ORKA1) and compared to larvae without overexpression. The compound was also observed in sequence and/or combination with a form of lipopolysaccharide (LPS) that transiently activates K2P channels. Different concentrations of Fluoxetine were tested, and it was also examined in cocktail with the LPS. At 25 μM Fluoxetine exposure, muscle in control larvae underwent depolarization, while muscles overexpressing K2P channels hyperpolarized; at 50 μM, however, much more variable responses were observed. The LPS caused hyperpolarization in both larval strains, but the effect was more transient in the Canton-S line than in the K2P overexpressors. Finally, LPS continued to cause hyperpolarization even in the presence of Fluoxetine, while Fluoxetine quickly depolarized the muscle during exposure to LPS. The cocktail showed a smaller effect on muscles overexpressing ORKA1 as compared to the controls, indicating that Fluoxetine does not block the ORKA1 subtype. This study is significant because it demonstrates how overexpression of K2P channels alters membrane response to LPS and Fluoxetine exposure.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"287 ","pages":"Article 110045"},"PeriodicalIF":3.9,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}