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27 pages, 10728 KiB

Open AccessArticle

Cuban Policosanol (Raydel^®) Exerts Higher Antioxidant and Anti-Glycation Activities than Chinese Policosanol (BOC Sciences) in Reconstituted High-Density Lipoproteins: In Vivo Anti-Inflammatory Activities in Zebrafish and Its Embryos

by Kyung-Hyun Cho, Ji-Eun Kim, Myeong-Sung Lee and Ashutosh Bahuguna

Pharmaceuticals 2024, 17(4), 406; https://doi.org/10.3390/ph17040406 - 22 Mar 2024

Viewed by 1073

Abstract

The present study compares sugarcane-wax purified policosanols sourced from Cuba (Raydel^®) and China (BOC Sciences) and utilized following the synthesis of reconstituted high-density lipoproteins (rHDL). The two policosanols exhibited distinctly different ingredient ratios of long-chain aliphatic alcohols, particularly 1-octacosanol (C28) and [...] Read more.

The present study compares sugarcane-wax purified policosanols sourced from Cuba (Raydel^®) and China (BOC Sciences) and utilized following the synthesis of reconstituted high-density lipoproteins (rHDL). The two policosanols exhibited distinctly different ingredient ratios of long-chain aliphatic alcohols, particularly 1-octacosanol (C28) and 1-tetratriacotanol (C34). After synthesizing rHDL with apolipoprotein A-I (apoA-I), the two policosanols bound well with phospholipid and apoA-I to form the discoidal rHDL. Notably, rHDL-1, containing Cuban policosanol, displayed the largest particle diameter at approximately 78 ± 3 nm. In contrast, both control rHDL (rHDL-0) and rHDL containing Chinese policosanol (rHDL-2) exhibited smaller particles, with diameters of approximately 58 ± 3 nm and 61 ± 2 nm, respectively. Furthermore, rHDL-1 demonstrated enhanced anti-glycation activity, safeguarding apoA-I from degradation within HDL, and displayed the antioxidant ability to inhibit LDL oxidation. A microinjection of each rHDL into zebrafish embryos in the presence of carboxymethyllysine (CML) revealed rHDL-1 to have the strongest antioxidant activity with the highest embryo survivability and normal developmental morphology. Dermal application to recover the wound revealed rHDL-1 to have the highest wound-healing activity (75%) and survivability (92%) in the cutaneous wound area in the presence of CML. In adult zebrafish, injecting CML (250 μg) caused acute death and hyperinflammation, marked by heightened neutrophil infiltration and interleukin (IL)-6 production in liver. However, co-administering rHDL-1 notably increased survival (85%) and exhibited strong anti-inflammatory properties, reducing IL-6 production while improving the blood lipid profile. However, a co-injection of rHDL-2 resulted in the lowest survivability (47%) with more hepatic inflammation. In conclusion, Cuban policosanol (Raydel^®) has more desirable properties for the in vitro synthesis of rHDL with stronger anti-glycation and antioxidant activities than those of Chinese policosanol (BOC Sciences). Moreover, Raydel-policosanol-integrated rHDL demonstrates a noteworthy effect on accelerated wound healing and robust anti-inflammatory properties, leading to increased survivability in zebrafish embryos and adults by effectively suppressing CML-induced hyperinflammation. Full article

(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery 2023)

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17 pages, 3296 KiB

Open AccessArticle

Decreased Brain Serotonin in rbfox1 Mutant Zebrafish and Partial Reversion of Behavioural Alterations by the SSRI Fluoxetine

by Maja R. Adel, Ester Antón-Galindo, Edurne Gago-Garcia, Angela Arias-Dimas, Concepció Arenas, Rafael Artuch, Bru Cormand and Noèlia Fernàndez-Castillo

Pharmaceuticals 2024, 17(2), 254; https://doi.org/10.3390/ph17020254 - 16 Feb 2024

Viewed by 883

Abstract

RBFOX1 functions as a master regulator of thousands of genes, exerting a pleiotropic effect on numerous neurodevelopmental and psychiatric disorders. A potential mechanism by which RBFOX1 may impact these disorders is through its modulation of serotonergic neurotransmission, a common target for pharmacological intervention [...] Read more.

RBFOX1 functions as a master regulator of thousands of genes, exerting a pleiotropic effect on numerous neurodevelopmental and psychiatric disorders. A potential mechanism by which RBFOX1 may impact these disorders is through its modulation of serotonergic neurotransmission, a common target for pharmacological intervention in psychiatric conditions linked to RBFOX1. However, the precise effects of RBFOX1 on the serotonergic system remain largely unexplored. Here we show that homozygous rbfox1^sa15940 zebrafish, which express a shorter, aberrant rbfox1 mRNA, have significantly reduced serotonin levels in telencephalon and diencephalon. We observed that the acute administration of fluoxetine partially reverses the associated behavioural alterations. The hyperactive phenotype and altered shoaling behaviour of the rbfox1^{sa15940/sa15940} zebrafish could be reversed with acute fluoxetine exposure in the Open Field and the Shoaling test, respectively. However, in the other paradigms, hyperactivity was not diminished, suggesting a distinct intrinsic motivation for locomotion in the different paradigms. Acute fluoxetine exposure did not reverse the alterations observed in the aggression and social novelty tests, suggesting the involvement of other neurological mechanisms in these behaviours. These findings underscore the importance of investigating the intricate working mechanisms of RBFOX1 in neurodevelopmental and psychiatric disorders to gain a better understanding of the associated disorders along with their pharmacological treatment. Full article

(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery 2023)

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26 pages, 13135 KiB

Open AccessArticle

Synergistic Anti-Inflammatory Activity of Apolipoprotein A-I and CIGB-258 in Reconstituted High-Density Lipoproteins (rHDL) against Acute Toxicity of Carboxymethyllysine in Zebrafish and Its Embryo

by Kyung-Hyun Cho, Ji-Eun Kim, Dae-Jin Kang, Maria del Carmen Dominguez-Horta and Gillian Martinez-Donato

Pharmaceuticals 2024, 17(2), 165; https://doi.org/10.3390/ph17020165 - 28 Jan 2024

Viewed by 1326

Abstract

CIGB-258 is a 3 kDa altered peptide ligand from heat shock protein (HSP) 60 that exhibits anti-inflammatory activity against the acute toxicity of carboxymethyllysine (CML) with antioxidant and anti-glycation activities via protection of high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I). It is necessary [...] Read more.

CIGB-258 is a 3 kDa altered peptide ligand from heat shock protein (HSP) 60 that exhibits anti-inflammatory activity against the acute toxicity of carboxymethyllysine (CML) with antioxidant and anti-glycation activities via protection of high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I). It is necessary to test a synergistic interaction between apoA-I and CIGB-258 in reconstituted high-density lipoproteins (rHDL). Several rHDLs were synthesized containing palmitoyloleoyl phosphatidylcholine (POPC), cholesterol, apoA-I, and CIGB-258 at molar ratios of 95:5:1:0, 95:5:1:0.1, 95:5:1:0.5, and 95:5:1:1 for rHDL-(1:0), rHDL-(1:0.1), rHDL-(1:0.5), and rHDL-(1:1), respectively. As the CIGB-258 content in rHDL was increased, the particle size of rHDL was 1.4-times higher than rHDL-(1:0) to rHDL-(1:1), from 60 nm to 83 nm, respectively. As the CIGB-258 content was increased, the rHDL showed the most resistance to isothermal denaturation by a urea treatment, and rHDL-(1:1) exhibited the highest structural stability and the strongest antioxidant ability against LDL oxidation. Co-treatment of rHDL-(1:0), rHDL-(1:0.5), and rHDL-(1:1) resulted in up to 10%, 24%, and 34% inhibition of HDL glycation, inhibition of HDL glycation, which was caused by the CML, with protection of apoA-I. Microinjection of each rHDL into zebrafish embryos in the presence of CML showed that a higher CIGB-258 content in rHDL was associated with higher survivability with the least inflammation and apoptosis. Furthermore, an intraperitoneal injection of rHDL and CML showed that a higher CIGB-258 content in rHDL was also associated with higher survivability of zebrafish and faster recovery of swimming ability. The rHDL-(1:1) group showed the lowest triglyceride, AST, and ALT serum levels with the least production of interleukin-6, oxidized product, and neutrophil infiltration in hepatic tissue. In conclusion, CIGB-258 could bind well to phospholipids and cholesterol to stabilize apoA-I in the rHDL structure against denaturation stress and larger particle sizes. The rHDL containing CIGB-258 enhanced the in vitro antioxidant ability against LDL oxidation, the anti-glycation activity to protect HDL, and the in vivo anti-inflammatory activity against CML toxicity in zebrafish adults and embryos. Overall, incorporating apoA-I and CIGB-258 in rHDL resulted in a synergistic interaction to enhance the structural and functional correlations in a dose-dependent manner of CIGB-258. Full article

(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery 2023)

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16 pages, 3259 KiB

Open AccessArticle

Canthin-6-One Inhibits Developmental and Tumour-Associated Angiogenesis in Zebrafish

by Mei Fong Ng, Juliana Da Silva Viana, Pei Jean Tan, Denver D. Britto, Sy Bing Choi, Sakurako Kobayashi, Norazwana Samat, Dedrick Soon Seng Song, Satoshi Ogawa, Ishwar S. Parhar, Jonathan W. Astin, Benjamin M. Hogan, Vyomesh Patel and Kazuhide S. Okuda

Pharmaceuticals 2024, 17(1), 108; https://doi.org/10.3390/ph17010108 - 12 Jan 2024

Viewed by 1258

Abstract

Tumour-associated angiogenesis play key roles in tumour growth and cancer metastasis. Consequently, several anti-angiogenic drugs such as sunitinib and axitinib have been approved for use as anti-cancer therapies. However, the majority of these drugs target the vascular endothelial growth factor A (VEGFA)/VEGF receptor [...] Read more.

Tumour-associated angiogenesis play key roles in tumour growth and cancer metastasis. Consequently, several anti-angiogenic drugs such as sunitinib and axitinib have been approved for use as anti-cancer therapies. However, the majority of these drugs target the vascular endothelial growth factor A (VEGFA)/VEGF receptor 2 (VEGFR2) pathway and have shown mixed outcome, largely due to development of resistances and increased tumour aggressiveness. In this study, we used the zebrafish model to screen for novel anti-angiogenic molecules from a library of compounds derived from natural products. From this, we identified canthin-6-one, an indole alkaloid, which inhibited zebrafish intersegmental vessel (ISV) and sub-intestinal vessel development. Further characterisation revealed that treatment of canthin-6-one reduced ISV endothelial cell number and inhibited proliferation of human umbilical vein endothelial cells (HUVECs), suggesting that canthin-6-one inhibits endothelial cell proliferation. Of note, canthin-6-one did not inhibit VEGFA-induced phosphorylation of VEGFR2 in HUVECs and downstream phosphorylation of extracellular signal-regulated kinase (Erk) in leading ISV endothelial cells in zebrafish, suggesting that canthin-6-one inhibits angiogenesis independent of the VEGFA/VEGFR2 pathway. Importantly, we found that canthin-6-one impairs tumour-associated angiogenesis in a zebrafish B16F10 melanoma cell xenograft model and synergises with VEGFR inhibitor sunitinib malate to inhibit developmental angiogenesis. In summary, we showed that canthin-6-one exhibits anti-angiogenic properties in both developmental and pathological contexts in zebrafish, independent of the VEGFA/VEGFR2 pathway and demonstrate that canthin-6-one may hold value for further development as a novel anti-angiogenic drug. Full article

(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery 2023)

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11 pages, 1067 KiB

Open AccessArticle

Lansoprazole Ameliorates Isoniazid-Induced Liver Injury

by Eri Wakai, Takashi Shiromizu, Shota Otaki, Junko Koiwa, Satoshi Tamaru and Yuhei Nishimura

Pharmaceuticals 2024, 17(1), 82; https://doi.org/10.3390/ph17010082 - 8 Jan 2024

Cited by 1 | Viewed by 1039

Abstract

Isoniazid is a first-line drug in antitubercular therapy. Isoniazid is one of the most commonly used drugs that can cause liver injury or acute liver failure, leading to death or emergency liver transplantation. Therapeutic approaches for the prevention of isoniazid-induced liver injury are [...] Read more.

Isoniazid is a first-line drug in antitubercular therapy. Isoniazid is one of the most commonly used drugs that can cause liver injury or acute liver failure, leading to death or emergency liver transplantation. Therapeutic approaches for the prevention of isoniazid-induced liver injury are yet to be established. In this study, we identified the gene expression signature for isoniazid-induced liver injury using a public transcriptome dataset, focusing on the differences in susceptibility to isoniazid in various mouse strains. We predicted that lansoprazole is a potentially protective drug against isoniazid-induced liver injury using connectivity mapping and an adverse event reporting system. We confirmed the protective effects of lansoprazole against isoniazid-induced liver injury using zebrafish and patients’ electronic health records. These results suggest that lansoprazole can ameliorate isoniazid-induced liver injury. The integrative approach used in this study may be applied to identify novel functions of clinical drugs, leading to drug repositioning. Full article

(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery 2023)

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23 pages, 2366 KiB

Open AccessArticle

In Vitro Anti-Diabetic, Anti-Inflammatory, Antioxidant Activities and Toxicological Study of Optimized Psychotria malayana Jack Leaves Extract

by Sharifah Nurul Akilah Syed Mohamad, Alfi Khatib, Siti Zaiton Mat So’ad, Qamar Uddin Ahmed, Zalikha Ibrahim, Tanzina Sharmin Nipun, Humaryanto Humaryanto, Mohamed F. AlAjmi, Shaden A. M. Khalifa and Hesham R. El-Seedi

Pharmaceuticals 2023, 16(12), 1692; https://doi.org/10.3390/ph16121692 - 5 Dec 2023

Viewed by 1586

Abstract

Psychotria malayana Jack (Family: Rubiaceae, local name: Salung) is a traditional herb used to treat diabetes. A previous study by our research group demonstrated that P. malayana methanolic and water extract exhibits significant potential as an effective agent for managing diabetes. Further research [...] Read more.

Psychotria malayana Jack (Family: Rubiaceae, local name: Salung) is a traditional herb used to treat diabetes. A previous study by our research group demonstrated that P. malayana methanolic and water extract exhibits significant potential as an effective agent for managing diabetes. Further research has been performed on the extraction optimization of this plant to enhance its inhibitory activity against α-glucosidase, a key enzyme associated with diabetes, and to reduce its toxicity. The objectives of this study are to evaluate the anti-diabetic, anti-inflammatory, and antioxidant properties of the optimized P. malayana leaf extract (OE), to evaluate its toxicity using a zebrafish embryo/larvae model, and to analyze its metabolites. The anti-diabetic effects were assessed by investigating α-glucosidase inhibition (AGI), while the inflammation inhibitory activity was performed using the soybean lipoxygenase inhibitory (SLOXI) test. The assessment of antioxidant activity was performed utilizing FRAP and DPPH assays. The toxicology study was conducted using the zebrafish embryo/larvae (Danio rerio) model. The metabolites present in the extracts were analyzed using GC-MS and LC-MS. OE demonstrated significant AGI and SLOXI activities, represented as 2.02 and 4.92 µg/mL for IC₅₀ values, respectively. It exhibited potent antioxidant activities as determined by IC₅₀ values of 13.08 µg/mL (using the DPPH assay) and 95.44 mmol TE/mg DW (using the FRAP assay), and also demonstrated an LC₅₀ value of 224.29 µg/mL, which surpasses its therapeutic index of 111.03. OE exhibited a higher therapeutic index compared to that of the methanol extract (13.84) stated in the previous state of the art. This suggests that OE exhibits a lower level of toxicity, making it safer for use, and has the potential to be highly effective in its anti-diabetic activity. Liquid chromatography–mass spectrometry (LC-MS) and gas chromatography–mass spectrometry (GC-MS) demonstrated the presence of several constituents in this extract. Among them, several compounds, such as propanoic acid, succinic acid, D-tagatose, myo-inositol, isorhamnetin, moracin M-3′-O-β-D-glucopyranoside, procyanidin B3, and leucopelargonidin, have been reported as possessing anti-diabetic and antioxidant activities. This finding offers great potential for future research in diabetes treatment. Full article

(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery 2023)

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16 pages, 2545 KiB

Open AccessArticle

Zebrafish Patient-Derived Xenograft Model as a Preclinical Platform for Uveal Melanoma Drug Discovery

by Jie Yin, Gangyin Zhao, Helen Kalirai, Sarah E. Coupland, Aart G. Jochemsen, Gabriel Forn-Cuní, Annemijn P. A. Wierenga, Martine J. Jager, B. Ewa Snaar-Jagalska and Arwin Groenewoud

Pharmaceuticals 2023, 16(4), 598; https://doi.org/10.3390/ph16040598 - 15 Apr 2023

Cited by 3 | Viewed by 2357

Abstract

Uveal melanoma (UM) is a rare malignant cancer of the eye, with up to 50% of patients dying from metastasis, for which no effective treatment is available. Due to the rarity of the disease, there is a great need to harness the limited [...] Read more.

Uveal melanoma (UM) is a rare malignant cancer of the eye, with up to 50% of patients dying from metastasis, for which no effective treatment is available. Due to the rarity of the disease, there is a great need to harness the limited material available from primary tumors and metastases for advanced research and preclinical drug screening. We established a platform to isolate, preserve, and transiently recover viable tissues, followed by the generation of spheroid cultures derived from primary UM. All assessed tumor-derived samples formed spheroids in culture within 24 h and stained positive for melanocyte-specific markers, indicating the retention of their melanocytic origin. These short-lived spheroids were only maintained for the duration of the experiment (7 days) or re-established from frozen tumor tissue acquired from the same patient. Intravenous injection of fluorescently labeled UM cells derived from these spheroids into zebrafish yielded a reproducible metastatic phenotype and recapitulated molecular features of the disseminating UM. This approach allowed for the experimental replications required for reliable drug screening (at least 2 individual biological experiments, with n > 20). Drug treatments with navitoclax and everolimus validated the zebrafish patient-derived model as a versatile preclinical tool for screening anti-UM drugs and as a preclinical platform to predict personalized drug responses. Full article

(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery 2023)

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13 pages, 2299 KiB

Open AccessArticle

Augmentation of Pectoral Fin Teratogenicity by Thalidomide in Human Cytochrome P450 3A-Expressing Zebrafish

by Wenjing Dong, Ippo Akasaka, Akifumi Komiyama, Tatsuro Nakamura, Naohiro Mizoguchi, Tasuku Nawaji, Shinichi Ikushiro, Makoto Kobayashi and Hiroki Teraoka

Pharmaceuticals 2023, 16(3), 368; https://doi.org/10.3390/ph16030368 - 28 Feb 2023

Cited by 2 | Viewed by 1761

Abstract

The pharmacological and toxicological effects of active metabolites of enzymes including cytochrome P450 (CYP) are important. While it has been believed for a long time that thalidomide causes characteristic limb malformation only in rabbits and primates including humans, the involvement of their CYP3A [...] Read more.

The pharmacological and toxicological effects of active metabolites of enzymes including cytochrome P450 (CYP) are important. While it has been believed for a long time that thalidomide causes characteristic limb malformation only in rabbits and primates including humans, the involvement of their CYP3A subtypes (CYP3As) has been suggested. Recently, however, it was reported that zebrafish were sensitive to thalidomide, showing defects of pectoral fins, homologous organs of forelimbs in mammals, as well as other deformities. In this study, we prepared human CYP3A7 (hCYP3A7)-expressing zebrafish (F0) using a transposon system. Thalidomide caused pectoral fin defects and other malformations including pericardial edema in hCYP3A7-expressing embryos/larvae but not in wild-type and hCYP1A1-expressing embryos/larvae. Thalidomide also reduced the expression of fibroblast growth factor 8 in pectoral fin buds in only hCYP3A7-expressing embryos/larvae. The results suggest the involvement of human-type CYP3A in thalidomide teratogenicity. Full article

(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery 2023)

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23 pages, 5615 KiB

Open AccessArticle

Discovering a Multi-Component Combination against Vascular Dementia from Danshen-Honghua Herbal Pair by Spectrum-Effect Relationship Analysis

by Peilin Zhang, Shiru He, Siqi Wu, Yi Li, Huiying Wang, Changyang Yan, Hua Yang and Ping Li

Pharmaceuticals 2022, 15(9), 1073; https://doi.org/10.3390/ph15091073 - 29 Aug 2022

Cited by 6 | Viewed by 1990

Abstract

The Danshen-Honghua (DH) herbal pair exhibits a synergistic effect in protecting the cerebrovascular system from ischemia/reperfusion injury, but the therapeutic effect on vascular dementia (VaD) has not been clarified, and the main active ingredient group has not been clarified. In this work, the [...] Read more.

The Danshen-Honghua (DH) herbal pair exhibits a synergistic effect in protecting the cerebrovascular system from ischemia/reperfusion injury, but the therapeutic effect on vascular dementia (VaD) has not been clarified, and the main active ingredient group has not been clarified. In this work, the chemical constituents in DH herbal pair extract were characterized by UHPLC-QTOF MS, and a total of 72 compounds were identified. Moreover, the DH herbal pair alleviated phenylhydrazine (PHZ)-induced thrombosis and improved bisphenol F (BPF)- and ponatinib-induced brain injury in zebrafish. Furthermore, the spectrum-effect relationship between the fingerprint of the DH herbal pair and the antithrombotic and neuroprotective efficacy was analyzed, and 11 chemical components were screened out as the multi-component combination (MCC) against VaD. Among them, the two compounds with the highest content were salvianolic acid B (17.31 ± 0.20 mg/g) and hydroxysafflor yellow A (15.85 ± 0.19 mg/g). Finally, we combined these 11 candidate compounds as the MCC and found that it could improve thrombosis and neuronal injury in three zebrafish models and rat bilateral common carotid artery occlusion (BCCAO) model, which had similar efficacy compared to the DH herbal pair. This study provides research ideas for the treatment of VaD and the clinical application of the DH herbal pair. Full article

(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery 2023)

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Review

Jump to: Research

25 pages, 1277 KiB

Open AccessReview

Illicit Drugs in Surface Waters: How to Get Fish off the Addictive Hook

by Halina Falfushynska, Piotr Rychter, Anastasiia Boshtova, Yuliia Faidiuk, Nadiia Kasianchuk and Piotr Rzymski

Pharmaceuticals 2024, 17(4), 537; https://doi.org/10.3390/ph17040537 - 22 Apr 2024

Viewed by 928

Abstract

The United Nations World Drug Report published in 2022 alarmed that the global market of illicit drugs is steadily expanding in space and scale. Substances of abuse are usually perceived in the light of threats to human health and public security, while the [...] Read more.

The United Nations World Drug Report published in 2022 alarmed that the global market of illicit drugs is steadily expanding in space and scale. Substances of abuse are usually perceived in the light of threats to human health and public security, while the environmental aspects of their use and subsequent emissions usually remain less explored. However, as with other human activities, drug production, trade, and consumption of drugs may leave their environmental mark. Therefore, this paper aims to review the occurrence of illicit drugs in surface waters and their bioaccumulation and toxicity in fish. Illicit drugs of different groups, i.e., psychostimulants (methamphetamines/amphetamines, cocaine, and its metabolite benzoylecgonine) and depressants (opioids: morphine, heroin, methadone, fentanyl), can reach the aquatic environment through wastewater discharge as they are often not entirely removed during wastewater treatment processes, resulting in their subsequent circulation in nanomolar concentrations, potentially affecting aquatic biota, including fish. Exposure to such xenobiotics can induce oxidative stress and dysfunction to mitochondrial and lysosomal function, distort locomotion activity by regulating the dopaminergic and glutamatergic systems, increase the predation risk, instigate neurological disorders, disbalance neurotransmission, and produce histopathological alterations in the brain and liver tissues, similar to those described in mammals. Hence, this drugs-related multidimensional harm to fish should be thoroughly investigated in line with environmental protection policies before it is too late. At the same time, selected fish species (e.g., Danio rerio, zebrafish) can be employed as models to study toxic and binge-like effects of psychoactive, illicit compounds. Full article

(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery 2023)

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19 pages, 1317 KiB

Open AccessReview

Screening of Mineralogenic and Osteogenic Compounds in Zebrafish—Tools to Improve Assay Throughput and Data Accuracy

by Joana T. Rosa, Marco Tarasco, Paulo J. Gavaia, M. Leonor Cancela and Vincent Laizé

Pharmaceuticals 2022, 15(8), 983; https://doi.org/10.3390/ph15080983 - 10 Aug 2022

Cited by 7 | Viewed by 2760

Abstract

Bone disorders affect millions of people worldwide and treatments currently available often produce undesirable secondary effects or have limited efficacy. It is therefore of the utmost interest for patients to develop more efficient drugs with reduced off-target activities. In the long process of [...] Read more.

Bone disorders affect millions of people worldwide and treatments currently available often produce undesirable secondary effects or have limited efficacy. It is therefore of the utmost interest for patients to develop more efficient drugs with reduced off-target activities. In the long process of drug development, screening and preclinical validation have recently gained momentum with the increased use of zebrafish as a model organism to study pathological processes related to human bone disorders, and the development of zebrafish high-throughput screening assays to identify bone anabolic compounds. In this review, we provided a comprehensive overview of the literature on zebrafish bone-related assays and evaluated their performance towards an integration into screening pipelines for the discovery of mineralogenic/osteogenic compounds. Tools available to standardize fish housing and feeding procedures, synchronize embryo production, and automatize specimen sorting and image acquisition/analysis toward faster and more accurate screening outputs were also presented. Full article

(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery 2023)

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