Displaying publications 101 - 120 of 171 in total

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  1. Muthuraman A, Nafisa K, Sowmya MS, Arpitha BM, Choedon N, Sandy CD, et al.
    Life Sci, 2019 Mar 04.
    PMID: 30844374 DOI: 10.1016/j.lfs.2019.03.002
    BACKGROUND: Cigarette smoke is exogenous modifiable factors to changes the neurovascular complication. The chronic exposure of cigarette smoke enhances neurocognitive dysfunction.

    AIMS: The present study is focused on evaluating the role of ambrisentan (selective endothelin-A receptor antagonist) on cigarette smoke-induced cognitive impairment in Danio rerio.

    MAIN METHODS: The cognitive dysfunction was developed by cigarette smoke exposure (CSE; 10 min in 25 ml of CSE per day) for five days. The selective endothelin-A receptor antagonist i.e., ambrisentan (2.5 to 5 mg/kg; i.p. for five consecutive days) was used for testing of CSE induced cognitive dysfunction. In addition, treatment of reference drug i.e., donepezil (10 mg/kg; i.p. for five consecutive days) was used for this cognitive function study. The cognitive functions were assessed by light and dark chamber; color recognition; partition preference; horizontal compartment; and T-Maze tests. Further, the CSE induced biomarkers changes of the zebrafish brain samples were estimated.

    KEY FINDINGS: The treatment of ambrisentan showed a potential ameliorative effect against the CSE induced cognitive functions along with attenuation of biochemical changes. The results are comparable to donepezil-treated groups.

    SIGNIFICANCE: Therefore, ambrisentan can be considered for the attenuation of CSE induced impairment neurocognitive functions due to its reduction of free radical scavenging and neuroinflammatory actions as well as regulation of cholinergic neurotransmitter functions.

    Matched MeSH terms: Zebrafish
  2. Alafiatayo AA, Lai KS, Syahida A, Mahmood M, Shaharuddin NA
    PMID: 30949217 DOI: 10.1155/2019/3807207
    Curcuma longa L. is a rhizome plant often used as traditional medicinal preparations in Southeast Asia. The dried powder is commonly known as cure-all herbal medicine with a wider spectrum of pharmaceutical activities. In spite of the widely reported therapeutic applications of C. longa, research on its safety and teratogenic effects on zebrafish embryos and larvae is still limited. Hence, this research aimed to assess the toxicity of C. longa extract on zebrafish. Using a reflux flask, methanol extract of C. longa was extracted and the identification and quantification of total flavonoids were carried out with HPLC. Twelve fertilized embryos were selected to test the embryotoxicity and teratogenicity at different concentration points. The embryos were exposed to the extract in the E3M medium while the control was only exposed to E3M and different developmental endpoints were recorded with the therapeutic index calculated using the ratio of LC50/EC50. C. longa extract was detected to be highly rich in flavonoids with catechin, epicatechin, and naringenin as the 3 most abundant with concentrations of 3,531.34, 688.70, and 523.83μg/mL, respectively. The toxicity effects were discovered to be dose-dependent at dosage above 62.50μg/mL, while, at 125.0μg/mL, mortality of embryos was observed and physical body deformities of larvae were recorded among the hatched embryos at higher concentrations. Teratogenic effect of the extract was severe at higher concentrations producing physical body deformities such as kink tail, bend trunk, and enlarged yolk sac edema. Finally, the therapeutic index (TI) values calculated were approximately the same for different concentration points tested. Overall, the result revealed that plants having therapeutic potential could also pose threats when consumed at higher doses especially on the embryos. Therefore, detailed toxicity analysis should be carried out on medicinal plants to ascertain their safety on the embryos and its development.
    Matched MeSH terms: Zebrafish
  3. Kumari Y, Choo BKM, Shaikh MF, Othman I
    Exp Ther Med, 2019 Aug;18(2):1407-1416.
    PMID: 31363378 DOI: 10.3892/etm.2019.7685
    Early life exposure to stress has been suggested to be a crucial factor for the development of the brain and its functions. It is well documented that childhood stress is a risk factor for sleep problems in adulthood. Piper betle L. leaf extract (PB) has been used in several traditional medicines to cure various ailments. Recently, PB has been proved to have antidepressant activity. The literature suggests that antidepressants affect the synthesis and release of melatonin through several mechanisms. Thus, this study investigated the potential role of PB for the treatment of sleep disruption after early life stress exposure. Firstly, dexamethasone (DEX) (2 and 20 mg/l for 24 h) was administered to zebrafish larvae on the 4th day post-fertilization (dpf) to induce early life stress. The effects of stress on behaviour during adulthood, melatonin level and stress-related gene expression (nfkb) in the brain were then studied. Next, the possible role of PB (10 and 30 mg/Kg) was studied by measuring its effect on behaviour and by quantifying the expression levels of several melatonin-related (MT1, MT2, aanat1, aanat2) and stress-related (nfkb) genes by qPCR. DEX-treated zebrafish exhibited anxious behaviour, along with a lower level of melatonin and a higher mRNA expression of nfkb. After treatment with PB, a similar effect on behaviour and gene expression levels as the melatonin treatment group (10 mg/kg; positive control) was seen in adult zebrafish. These molecular confirmations of the observed behavioural effects of the PB indicate a possible role in the treatment of early life stress-induced sleep disruption.
    Matched MeSH terms: Zebrafish
  4. Raza H, Abbasi MA, Aziz-Ur-Rehman, Siddiqui SZ, Hassan M, Abbas Q, et al.
    Bioorg Chem, 2020 01;94:103445.
    PMID: 31826809 DOI: 10.1016/j.bioorg.2019.103445
    In the current research work, different N-(substituted-phenyl)-4-{(4-[(E)-3-phenyl-2-propenyl]-1-piperazinyl}butanamides have been synthesized according to the protocol described in scheme 1. The synthesis was initiated by reacting various substituted anilines (1a-e) with 4-chlorobutanoyl chloride (2) in aqueous basic medium to give various electrophiles, 4-chloro-N-(substituted-phenyl)butanamides (3a-e). These electrophiles were then coupled with 1-[(E)-3-phenyl-2-propenyl]piperazine (4) in polar aprotic medium to attain the targeted N-(substituted-phenyl)-4-{(4-[(E)-3-phenyl-2-propenyl]-1-piperazinyl}butanamides (5a-e). The structures of all derivatives were identified and characterized by proton-nuclear magnetic resonance (1H NMR), carbon-nuclear magnetic resonance (13C NMR) and Infra-Red (IR) spectral data along with CHN analysis. The in vitro inhibitory potential of these butanamides was evaluated against Mushroom tyrosinase, whereby all compounds were found to be biologically active. Among them, 5b exhibited highest inhibitory potential with IC50 value of 0.013 ± 0.001 µM. The same compound 5b was also assayed through in vivo approach, and it was explored that it significantly reduced the pigments in zebrafish. The in silico studies were also in agreement with aforesaid results. Moreover, these molecules were profiled for their cytotoxicity through hemolytic activity, and it was found that except 5e, all other compounds showed minimal toxicity. The compound 5a also exhibited comparable results. Hence, some of these compounds might be worthy candidates for the formulation and development of depigmentation drugs with minimum side effects.
    Matched MeSH terms: Zebrafish
  5. Patsiou D, Del Rio-Cubilledo C, Catarino AI, Summers S, Mohd Fahmi A, Boyle D, et al.
    Sci Total Environ, 2020 May 01;715:136941.
    PMID: 32041050 DOI: 10.1016/j.scitotenv.2020.136941
    Lead-halide perovskite nanoparticles (NPs) are a new technology, and investigation of toxicity is of considerable importance due to the potential lead (Pb) release into the environment. The aim of the study was to investigate aqueous and dietary toxicity of Pb-halide perovskite NP and Pb in zebrafish Danio rerio. Perovskite NP toxicity was evaluated in zebrafish by mortality, gene expression, histopathology, and phylogenetic analysis of gut microbiota. Zebrafish larvae were exposed to five Pb-halide perovskite NPs in parallel with Pb(NO3)2 exposures, and zebrafish adults were exposed to the three perovskite NPs that caused the strongest effect and Pb(NO3)2. No median lethal concentration (LC50) was observed for zebrafish larvae exposed to up to 200 mg/L of perovskite NPs for 96 h. Mortality, metallothionein 2 (mt2) and δ-aminolevulinic acid dehydratase (ala-d) gene expression (24-h exposure) in zebrafish larvae after aqueous perovskite NPs exposures did not differ from total Pb concentration - response curves. The lack of differences in mortality and gene expression between perovskite NPs and soluble Pb after aqueous exposure suggest that toxicity from perovskite NPs can be attributed to bioavailable Pb rather than nano-specific effects. Induction of mt2 and reduction of ala-d expression levels in liver tissues showed Pb bioavailability after 2-d and 4-d dietary exposure to perovskite-spiked feeds. Changes in gut microbiota of adult zebrafish were detected after 14-d exposure to Pb-spiked food, but no changes were detected from perovskite-NP spiked food. The phylogenetic analysis identified different microbiome profiles of Pb-fed fish compared to perovskite-fed fish suggesting a different mechanism of toxicity. Exposure to Pb-halide perovskite NPs led to absorption of Pb likely from release of Pb ions rather than absorption of NPs. Pb-halide perovskite NPs can release bioavailable Pb and this needs to be considered during the development of this technology.
    Matched MeSH terms: Zebrafish
  6. Murugesu S, Khatib A, Ahmed QU, Ibrahim Z, Uzir BF, Benchoula K, et al.
    Toxicol Rep, 2019;6:1148-1154.
    PMID: 31993329 DOI: 10.1016/j.toxrep.2019.10.020
    Clinacanthus nutans, an herbal shrub belonging to the Acanthaceae family, is traditionally used as a functional food to treat various ailments in Malaysia and Indonesia. Although the polar fraction of this plant shows non-toxic effect, the toxicity of the non-polar extract is not reported so far. The present study aimed to assess the toxic effect and determine the lethal concentration of this non-polar fraction using zebrafish embryos. The n-hexane fraction was partitioned from the crude extract of C. nutans obtained using 80% methanolic solution. After spawning of the adult male and female zebrafish, the eggs were collected, transferred into a 96-well plate and incubated with the n-hexane fraction at concentrations of 15.63 μg/ml, 31.25 μg/ml, 62.5 μg/ml, 125 μg/ml, 250 μg/ml and 500 μg/ml in 2% DMSO. The survival and sublethal endpoint were assessed, the mortality and hatchability rates were calculated based on microscopic observation, while the heartbeat rate was measured using DanioScope software. The median lethal concentration (LC50) of the C. nutans n-hexane fraction, which was determined using probit analysis, was calculated to be 75.49 μg/mL, which is harmful. Moreover, gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of palmitic acid, phytol, hexadecanoic acid, 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol and stigmasterol in the n-hexane fraction.
    Matched MeSH terms: Zebrafish
  7. Chung YS, Choo BKM, Ahmed PK, Othman I, Shaikh MF
    Biomedicines, 2020 Jul 02;8(7).
    PMID: 32630817 DOI: 10.3390/biomedicines8070191
    The anticonvulsive potential of proteins extracted from Orthosiphon stamineus leaves (OSLP) has never been elucidated in zebrafish (Danio rerio). This study thus aims to elucidate the anticonvulsive potential of OSLP in pentylenetetrazol (PTZ)-induced seizure model. Physical changes (seizure score and seizure onset time, behavior, locomotor) and neurotransmitter analysis were elucidated to assess the pharmacological activity. The protective mechanism of OSLP on brain was also studied using mass spectrometry-based label-free proteomic quantification (LFQ) and bioinformatics. OSLP was found to be safe up to 800 µg/kg and pre-treatment with OSLP (800 µg/kg, i.p., 30 min) decreased the frequency of convulsive activities (lower seizure score and prolonged seizure onset time), improved locomotor behaviors (reduced erratic swimming movements and bottom-dwelling habit), and lowered the excitatory neurotransmitter (glutamate). Pre-treatment with OSLP increased protein Complexin 2 (Cplx 2) expression in the zebrafish brain. Cplx2 is an important regulator in the trans-SNARE complex which is required during the vesicle priming phase in the calcium-dependent synaptic vesicle exocytosis. Findings in this study collectively suggests that OSLP could be regulating the release of neurotransmitters via calcium-dependent synaptic vesicle exocytosis mediated by the "Synaptic Vesicle Cycle" pathway. OSLP's anticonvulsive actions could be acting differently from diazepam (DZP) and with that, it might not produce the similar cognitive insults such as DZP.
    Matched MeSH terms: Zebrafish
  8. Murugan K, Anitha J, Dinesh D, Suresh U, Rajaganesh R, Chandramohan B, et al.
    Ecotoxicol Environ Saf, 2016 Oct;132:318-28.
    PMID: 27344400 DOI: 10.1016/j.ecoenv.2016.06.021
    Mosquitoes are arthropods of huge medical and veterinary relevance, since they vector pathogens and parasites of public health importance, including malaria, dengue and Zika virus. Currently, nanotechnology is considered a potential eco-friendly approach in mosquito control research. We proposed a novel method of biofabrication of silver nanoparticles (AgNP) using chitosan (Ch) from crab shells. Ch-AgNP nanocomposite was characterized by UV-vis spectroscopy, FTIR, SEM, EDX and XRD. Ch-AgNP were tested against larvae and pupae of the malaria vector Anopheles stephensi obtaining LC50 ranging from 3.18 ppm (I) to 6.54 ppm (pupae). The antibacterial properties of Ch-AgNP were proved against Bacillus subtilis, Klebsiella pneumoniae and Salmonella typhi, while no growth inhibition was reported in assays conducted on Proteus vulgaris. Concerning non-target effects, in standard laboratory considtions the predation efficiency of Danio rerio zebrafishes was 68.8% and 61.6% against I and II instar larvae of A. stephensi, respectively. In a Ch-AgNP-contaminated environment, fish predation was boosted to 89.5% and 77.3%, respectively. Quantitative analysis of antioxidant enzymes SOD, CAT and LPO from hepatopancreas of fresh water crabs Paratelphusa hydrodromous exposed for 16 days to a Ch-AgNP-contaminated aquatic environment were conducted. Notably, deleterious effects of Ch-AgNP contaminating aquatic enviroment on the non-target crab P. hydrodromous were observed, particularly when doses higher than 8-10ppm are tested. Overall, this research highlights the potential of Ch-AGNP for the development of newer control tools against young instar populations of malaria mosquitoes, also highlighting some risks concerned the employ of nanoparticles in aquatic environments.
    Matched MeSH terms: Zebrafish
  9. Hayati F, Chabib L, Fauzi IS, Awaluddin R, Sumayya, Faizah WS, et al.
    J Pharm Bioallied Sci, 2020 10 08;12(4):457-461.
    PMID: 33679093 DOI: 10.4103/jpbs.JPBS_297_19
    Introduction: Pegagan is a traditional medicinal plant with three major bioactive properties, triterpenoid, steroids, and saponin. It has the properties of antioxidant, antistress, and wound healing. Pegagan extract is prepared in self-nanoemulsifying drug delivery systems (SNEDDS) to overcome the problem of low water-solubility level.

    Objectives: This study aimed to observe the effect of pegagan ethanolic extract SNEDDS on the development of zebrafish embryos.

    Materials and Methods: This study used 12 sets of zebrafish embryos presented in five sets of extract SNEDDS with different concentrations, that is, 20, 10, 5, 2.5, and 1.25 μg, five sets of SNEDDS without extract with different concentrations, that is, 20, 10, 5, 2.5, and 1.25 μg, a set of positive control (3.4-DCA 4 mg/L) with one control set (diluted with water), and a negative control (SNEDDS without extract). The procedure was conducted for 96 h with observations every 24 h. The parameters observed were embryonic coagulation, formation of somites, detachment of tail bud from the yolk, and abnormality of embryo.

    Results: The results showed that in 96 h the 20ppm concentration caused 100% mortality. Embryo abnormality appeared as coagulation of embryo, somite malformation, and abnormal tail.

    Discussion: There is a correlation between the concentration of SNEDDS and the incidence of embryo coagulation. The malformation in the group of pegagan extract SNEDDS is characterized by cardiac edema, somite malformation, and abnormal tail.

    Conclusion: Pegagan ethanolic extract SNEDDS of 20ppm can inhibit the development of zebrafish embryos.

    Matched MeSH terms: Zebrafish
  10. Ahmad Ashraful Hadi Abdul Ghafor, Nurhuda Elias, Suhaili Shams, Faizah Md Yasin, Sarchio, Seri Narti Edayu
    MyJurnal
    Gallic acid (GA) is a phenolic compound found in almost all plants and has been reported to possess powerful health benefits such as anti-oxidant, anti-inflammatory, anti-cancer, and anti-diabetic properties. However, GA suffers a short half-life when administered in vivo. Recent studies have employed graphene oxide (GO), a biocompatible and cost-effective graphene derivative, as a nanocarrier for GA. However, the toxicity effect of this formulated nano-compound has not been fully studied. Thus, the present study aims to evaluate the toxicity and teratogenicity of GA loaded GO (GAGO) against zebrafish embryogenesis to further advance the development of GA as a therapeutic agent. GAGO was exposed to zebrafish embryos (n ≥ 10; 24hr post fertilization (hpf)) at different concentrations (0-500 μg/ml). The development of zebrafish was observed and recorded twice daily for four days. The toxicity of pure GO and GA was also observed at similar concentrations. Distilled water was used as control throughout the experiment. A significantly high mortality rate, delayed hatching rate and low heartbeat were recorded in embryos exposed to GO at concentrations of ≥ 150 μg/ml at 48 hr (p
    Matched MeSH terms: Zebrafish
  11. Ikram Ismail, Siti-Ariza Aripin
    MyJurnal
    Danio rerio or commonly known as zebrafish are a very popular fish among scientists and also a well-known vertebrate model species widely used in research. Zebrafish, are also a popular species among aquarists and have been put in aquariums all around the world as ornamental fish. The acid rain phenomenon has lowered the pH level of the wild habitat of zebrafish by shifting it to a more acidic pH level. This study was carried out to observe the effect of low pH level on the reproductive performance of zebrafish. The zebrafish were quarantined for a week to make sure they were healthy to be used in the experiment. The zebrafish were reared continuously for 14 days in three different pH treatments T1 (pH 2-4), T2 (pH 4-6), T3 (pH 6-8)). T3 (pH 6-8) was used as the control treatment. Hydrochloric acid (HCl) was used to control the pH level of treatments T1 (pH 2-4), T2 (pH 4-6), T3 (pH 6-8) with three replicates of each treatment. The male chasing female frequency was significant (p: 0.0001) and the data showed the highest frequency (2568.000±140.6272) at treatment 3 (pH 6-8). For the spawning frequency of zebrafish, treatment 3 (pH 6-8) showed the highest value (4.000±0.5774) followed by treatment 2 and treatment 1 and the data was significant (p: 0.0004). The fertilisation rate of the zebrafish was significant (p: 0.0001) and the highest was shown at T2 (pH 4-6) with 89.8018±0.3782, followed by T3 and treatment T1. For the hatching rate of the zebrafish, the data collected were significant (p: 0.0002) and the highest value of 2.9350±0.4070 was shown at T3 (pH 6-8), followed by T2 (pH 4-6) and T1 (pH 2-4). The overall result showed that pH 2-4 had the worst effect on the reproductive performance of zebrafish. Therefore, low pH has a significant effect on reducing the reproductive performance of zebrafish. The local fish population can be affected by the decrease of pH level due to acid rains and chemical waste pollution.
    Matched MeSH terms: Zebrafish
  12. Saleh Hodin NA, Chong SG, Bakar NA, Fahmi MSAM, Ramlan NF, Hamid NNAZZ, et al.
    Birth Defects Res, 2023 Oct 01;115(16):1475-1485.
    PMID: 37507847 DOI: 10.1002/bdr2.2227
    Valproic acid (VPA) is a widely prescribed antiepileptic drug with various medicinal efficacies. Accumulated evidence implied that prenatal exposure to VPA is highly associated with autism spectrum disorder (ASD). In this study, the zebrafish were exposed to a set of VPA concentrations (0, 5, 10, 20, 40, 80, 160, 320, 640, 1280, and 2560 μM) at 5 h post fertilization (hpf) to 120 hpf. The adverse effects of VPA were extensively studied through the evaluations on the mortality, heartbeats, spontaneous tail coiling, and hatching rate. Morphological observations were conducted at 120 hpf, following the exposure termination. Basic locomotor responses and anxiety-like behavioral alterations evaluated for behavioral impairments are the hallmark feature of ASD. The exposure to VPA at teratogenic concentrations reduced the aforementioned parameters in a dose-dependent manner (p ≤ .05). At the selected non-teratogenic concentrations of VPA, the treated larvae demonstrated profound alterations of basic locomotor responses. No significant changes of anxiety and thigmotactic behaviors were observed on the VPA-treated fish compared to the control (p ≥ .005). This study depicted that embryonic zebrafish exposure to VPA produced significant toxicity and teratogenicity effects as well as the alterations of basic behavioral responses. Overall, this study provides a fundamental insight of the toxicity effects at morphological and behavioral levels to facilitate the understanding of ASD mechanisms at different molecular levels.
    Matched MeSH terms: Zebrafish
  13. Ahda M, Jaswir I, Khatib A, Ahmed QU, Mahfudh N, Ardini YD, et al.
    Sci Rep, 2023 Oct 09;13(1):17012.
    PMID: 37813908 DOI: 10.1038/s41598-023-43251-2
    Ocimum aristatum, commonly known as O. stamineus, has been widely studied for its potential as an herbal medicine candidate. This research aims to compare the efficacy of water and 100% ethanolic extracts of O. stamineus as α-glucosidase inhibitors and antioxidants, as well as toxicity against zebrafish embryos. Based on the study findings, water extract of O. stamineus leaves exhibited superior inhibition activity against α-glucosidase, ABTS, and DPPH, with IC50 values of approximately 43.623 ± 0.039 µg/mL, 27.556 ± 0.125 µg/mL, and 95.047 ± 1.587 µg/mL, respectively. The major active compounds identified in the extract include fatty acid groups and their derivates such as linoleic acid, α-eleostearic acid, stearic acid, oleanolic acid, and corchorifatty acid F. Phenolic groups such as caffeic acid, rosmarinic acid, 3,4-Dihydroxybenzaldehyde, norfenefrine, caftaric acid, and 2-hydroxyphenylalanine and flavonoids and their derivates including 5,7-Dihydroxychromone, 5,7-Dihydroxy-2,6-dimethyl-4H-chromen-4-one, eupatorin, and others were also identified in the extract. Carboxylic acid groups and triterpenoids such as azelaic acid and asiatic acid were also present. This study found that the water extract of O. stamineus is non-toxic to zebrafish embryos and does not affect the development of zebrafish larvae at concentrations lower than 500 µg/mL. These findings highlight the potential of the water extract of O. stamineus as a valuable herbal medicine candidate, particularly for its potent α-glucosidase inhibition and antioxidant properties, and affirm its safety in zebrafish embryos at tested concentrations.
    Matched MeSH terms: Zebrafish
  14. Aldurrah Z, Mohd Kauli FS, Abdul Rahim N, Zainal Z, Afzan A, Al Zarzour RH, et al.
    PMID: 37301417 DOI: 10.1016/j.cbpc.2023.109678
    Andrographis paniculata (A. paniculata) showed an anti-depressive effect in rodent models. Zebrafish has recently emerged as a worthy complementary translational model for antidepressant drug discovery study. This study investigates the anti-depressive effect of A. paniculata extract and andrographolide in the chronic unpredictable stress (CUS)- zebrafish model. Four groups of zebrafish (n = 10/group), i.e. control, CUS (stressed, untreated), CUS + A. paniculata (100 mg/L) and CUS + fluoxetine (0.01 mg/L) were assessed in open-field and social interaction tests, 24 h after treatment. After extract screening, behavioural and cortisol analysis of andrographolide (5, 25 and 50 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) were evaluated. Before the behavioural study, acute toxicity and characterization of A. paniculata extract using UHPLC-ESI-MS/MS were performed. A significant reduction in freezing duration was found in A. paniculata- (t-test, p = 0.0234) and fluoxetine-treated groups (t-test, p 
    Matched MeSH terms: Zebrafish
  15. Parhar IS, Ogawa S, Ubuka T
    PMID: 27065948 DOI: 10.3389/fendo.2016.00028
    Social behaviors are key components of reproduction, because they are essential for successful fertilization. Social behaviors, such as courtship, mating, and aggression, are strongly associated with sex steroids, such as testosterone, estradiol, and progesterone. Secretion of sex steroids from the gonads is regulated by the hypothalamus-pituitary-gonadal (HPG) axis in vertebrates. Gonadotropin-releasing hormone (GnRH) is a pivotal hypothalamic neuropeptide that stimulates gonadotropin release from the pituitary. In recent years, the role of neuropeptides containing the C-terminal Arg-Phe-NH2 (RFamide peptides) has been emphasized in vertebrate reproduction. In particular, two key RFamide peptides, kisspeptin and gonadotropin-inhibitory hormone (GnIH), emerged as critical accelerator and suppressor of gonadotropin secretion. Kisspeptin stimulates GnRH release by directly acting on GnRH neurons, whereas GnIH inhibits gonadotropin release by inhibiting kisspeptin, GnRH neurons, or pituitary gonadotropes. These neuropeptides can regulate social behavior by regulating the HPG axis. However, distribution of neuronal fibers of GnRH, kisspeptin, and GnIH neurons is not limited within the hypothalamus, and the existence of extrahypothalamic neuronal fibers suggests direct control of social behavior within the brain. It has traditionally been shown that central administration of GnRH can stimulate female sexual behavior in rats. Recently, it was shown that Kiss1, one of the paralogs of kisspeptin peptide family, regulates fear responses in zebrafish and GnIH inhibits sociosexual behavior in birds. Here, we highlight recent findings regarding the role of GnRH, kisspeptin, and GnIH in the regulation of social behaviors in fish, birds, and mammals and discuss their importance in future biological and biomedical research.
    Matched MeSH terms: Zebrafish
  16. Nathan FM, Ogawa S, Parhar IS
    J Neurochem, 2015 Nov;135(4):814-29.
    PMID: 26250886 DOI: 10.1111/jnc.13273
    The habenula, located on the dorsal thalamic surface, is an emotional and reward processing center. As in the mammalian brain, the zebrafish habenula is divided into dorsal (dHb) and ventral (vHb) subdivisions that project to the interpeduncular nucleus and median raphe (MR) respectively. Previously, we have shown that kisspeptin 1 (Kiss1) expressing in the vHb, regulates the serotonin (5-HT) system in the MR. However, the connectivity between the Kiss1 neurons and the 5-HT system remains unknown. To resolve this issue, we generated a specific antibody against zebrafish Kiss1 receptor (Kiss-R1); using this primary antibody we found intense immunohistochemical labeling in the ventro-anterior corner of the MR (vaMR) but not in 5-HT neurons, suggesting the potential involvement of interneurons in 5-HT modulation by Kiss1. Double-fluorescence labeling showed that the majority of habenular Kiss1 neurons are glutamatergic. In the MR region, Kiss1 fibers were mainly seen in close association with glutamatergic neurons and only scarcely within GABAergic and 5-HT neurons. Our findings indicate that the habenular Kiss1 neurons potentially modulate the 5-HT system primarily through glutamatergic neurotransmission via as yet uncharacterized interneurons. The neuropeptide kisspeptin (Kiss1) play a key role in vertebrate reproduction. We have previously shown modulatory role of habenular Kiss1 in the raphe serotonin (5-HT) systems. This study proposed that the habenular Kiss1 neurons modulate the 5-HT system primarily through glutamatergic neurotransmission, which provides an important insight for understanding of the modulation of 5-HT system by the habenula-raphe pathway.
    Matched MeSH terms: Zebrafish; Zebrafish Proteins/genetics; Zebrafish Proteins/metabolism*
  17. Abdul Basit NS, Yap MMC, Mah YK, Ogawa S
    Expert Opin Drug Discov, 2026 Nov;21(11):1227-1241.
    PMID: 42847163 DOI: 10.1080/17460441.2026.2743766
    INTRODUCTION: Anxiety disorders are among the most prevalent psychiatric conditions worldwide, yet the development of novel anxiolytic therapies remains limited by poor translational success and the complexity of anxiety neurobiology. Zebrafish (Danio rerio) have emerged as a valuable vertebrate model bridging high-throughput in vitro screening and mammalian preclinical studies by combining whole-organism physiology with scalable phenotypic screening.

    AREAS COVERED: This review evaluates advances in zebrafish models for anxiolytic drug discovery, focusing on features supporting their construct and predictive validity. Larval zebrafish enable high-throughput behavioral and imaging-based screening, whereas adults provide more complex behavioral phenotypes and translational validation. Genetically engineered models, automated behavioral tracking, functional imaging, and molecular profiling further support mechanism-based drug discovery. A targeted search of PubMed/MEDLINE, Web of Science, and Scopus identified current and foundational studies on zebrafish anxiety models, neurobiology, behavioral assays, and drug discovery.

    EXPERT OPINION: Integration of behavioral phenotyping with genetics, multi-omics, functional imaging, and artificial intelligence could transform zebrafish from a screening organism into an integrated platform for precision psychiatry and personalized neuropsychopharmacological drug discovery, and improving translation across experimental scales. Zebrafish are best positioned as an efficient intermediate translational model that accelerates mechanism-based anxiolytic discovery while complementing, rather than replacing, mammalian preclinical studies.

    Matched MeSH terms: Zebrafish
  18. Ooi KK, Yeo CI, Mahandaran T, Ang KP, Akim AM, Cheah YK, et al.
    J Inorg Biochem, 2017 01;166:173-181.
    PMID: 27865929 DOI: 10.1016/j.jinorgbio.2016.11.008
    Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death. Cell cycle analysis showed the majority of treated HT-29 cells were arrested at the G2/M checkpoint after 24h; results of both assays were confirmed by changes in populations of relevant genes (PCR array analysis). Cell invasion studies showed inhibition of metastasis through Matrigel™ matrix to 17-22% cf. untreated cells. LC50values were determined in zebrafish (8.36, 8.17, and 7.64μM for 1-3). Finally, the zebrafish tolerated doses of 1 and 2 up to 0.625μM, and 3 was tolerated at even higher doses of up to 1.25μM.
    Matched MeSH terms: Zebrafish/embryology*
  19. Othman N, Nagoor NH
    Int J Oncol, 2019 01;54(1):306-314.
    PMID: 30365047 DOI: 10.3892/ijo.2018.4602
    The silencing of Bcl‑xL in the non‑small cell lung cancer (NSCLC) cell line, A549, downregulates miR‑361‑5p expression. This study aimed to determine the biological effects of miR‑361‑5p on NSCLC, and to elucidate the molecular mechanisms through which apoptosis is regulated. MicroRNA (miRNA or miR) functional analyses were performed via transfection of miR‑361‑5p mimics and inhibitors, demonstrating that the inhibition of miR‑361‑5p induced the apoptosis of NSCLC cells. To elucidate the function of miR‑361‑5p in vivo, cells transfected with miR‑361‑5p inhibitors were microinjected into zebrafish embryos, and immunostained using antibodies to detect the active form of caspase‑3. Co-transfection with siBcl‑xL and miR‑361‑5p mimics illustrated the association between Bcl‑xL, miR‑361‑5p and apoptosis; miR‑361‑5p mimics blocked the apoptosis initiated by siBcl‑xL. Luciferase reporter assays identified mothers against decapentaplegic homolog 2 (SMAD2) as a novel target of miR‑361‑5p and the reduction of its protein level was validated by western blot analysis. To confirm the molecular mechanisms through which apoptosis is regulated, gene rescue experiments revealed that the ectopic expression of SMAD2 attenuated the inhibitory effects on apoptosis induced by miR‑361‑5p. In this study, to the best of our knowledge, we provide the first evidence that miR‑361‑5p functions as an oncomiR in A549 and SK‑LU‑1 cells through the regulation of SMAD2, suggesting that miR‑361‑5p may be employed as a potential therapeutic target for the miRNA-based therapy of NSCLC.
    Matched MeSH terms: Zebrafish/embryology
  20. Abdullah MA, Lee YR, Mastuki SN, Leong SW, Wan Ibrahim WN, Mohammad Latif MA, et al.
    Bioorg Chem, 2020 11;104:104277.
    PMID: 32971414 DOI: 10.1016/j.bioorg.2020.104277
    A series of aminated- (1-9) and sulfonamide-containing diarylpentadienones (10-18) were synthesized, structurally characterized, and evaluated for their in vitro anti-diabetic potential on α-glucosidase and DPP-4 enzymes. It was found that all the new molecules were non-associated PAINS compounds. The sulfonamide-containing series (compounds 10-18) selectively inhibited α-glucosidase over DPP-4, in which compound 18 demonstrated the highest activity with an IC50 value of 5.69 ± 0.5 µM through a competitive inhibition mechanism. Structure-activity relationship (SAR) studies concluded that the introduction of the trifluoromethylbenzene sulfonamide moiety was essential for the suppression of α-glucosidase. The most active compound 18, was then further tested for in vivo toxicities using the zebrafish animal model, with no toxic effects detected in the normal embryonic development, blood vessel formation, and apoptosis of zebrafish. Docking simulation studies were also carried out to better understand the binding interactions of compound 18 towards the homology modeled α -glucosidase and the human lysosomal α -glucosidase enzymes. The overall results suggest that the new sulfonamide-containing diarylpentadienones, compound 18, could be a promising candidate in the search for a new α-glucosidase inhibitor, and can serve as a basis for further studies involving hit-to-lead optimization, in vivo efficacy and safety assessment in an animal model and mechanism of action for the treatment of T2DM patients.
    Matched MeSH terms: Zebrafish/embryology
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