Neurotoxicity of aluminium chloride and okadaic acid in zebrafish: Insights into Alzheimer's disease models through anxiety and locomotion testing, and acute toxicity assessment with Litsea garciae bark's methanolic extract
Alzheimer's disease (AD) is a complicated neurodegenerative disorder that presents significant challenges for the development of effective therapeutic interventions. Understanding disease mechanisms and exploring potential treatments require the use of animal models that accurately replicate th...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Journal of King Saud University: Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1018364723002690 |
| _version_ | 1797687694733606912 |
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| author | Siti Zaleha Raduan Qamar Uddin Ahmed Abdul Razak Kasmuri Muhamad Rusdi Ahmad Rusmili Wan Azizi Wan Sulaiman Mohd Farooq Shaikh Muhammad Hamdi Mahmood Syed Najmul Hejaz Azmi Mohammad Z. Ahmed Shadab Kazmi |
| author_facet | Siti Zaleha Raduan Qamar Uddin Ahmed Abdul Razak Kasmuri Muhamad Rusdi Ahmad Rusmili Wan Azizi Wan Sulaiman Mohd Farooq Shaikh Muhammad Hamdi Mahmood Syed Najmul Hejaz Azmi Mohammad Z. Ahmed Shadab Kazmi |
| author_sort | Siti Zaleha Raduan |
| collection | DOAJ |
| description | Alzheimer's disease (AD) is a complicated neurodegenerative disorder that presents significant challenges for the development of effective therapeutic interventions. Understanding disease mechanisms and exploring potential treatments require the use of animal models that accurately replicate the pathology of AD. In this study, we investigated the potential of two neurotoxin inducers, aluminium chloride (AlCl3) and okadaic acid (OKA), to validate the zebrafish as a model organism for AD. AD can impact locomotor activity and induce anxiety-like behaviors. To assess these behaviors, a 6-minute novel tank test was conducted. Zebrafish were administered with low, medium, or high doses of neurotoxic agent (AlCl3 or OKA) intraperitoneally twice weekly for 21 days. Behavioral activities were recorded at three time points: day 7 (short duration), day 14 (moderate duration), and day 21 (extended duration). The behavioral task required the evaluation of four endpoints. Methanolic extract of Litsea garciae bark was selected as a potential plant for the treatment of AD in this study, based on its previously demonstrated antioxidant effect. However, the acute toxicity of this plant has not been previously assessed. Therefore, this research was aimed to investigate the acute toxicity of the L. garciae bark’s methanolic extract in adult zebrafish. The extract was immersed in a static system following OECD Test Guideline No. 203, and the acute toxicity test involved monitoring the adult zebrafish for 96 h for any deaths or apparent abnormalities. Regarding the behavioural task, the groups induced with 100 nM of OKA demonstrated significant differences in all measured parameters compared to the control group at the 21-day time point. In contrast, none of the parameters were significantly different between the AlCl3-induced groups and the control group at any of the three time points (7, 14, or 21 days). Regarding acute toxicity, neither the test group (100 mg/L) nor the control group recorded any deaths or abnormalities. Therefore, no LC50 value could be determined. These findings confirm the acceptance of OKA as an inducer in the zebrafish model of AD and highlight the significance of the safe and non-toxic nature of L. garciae bark's methanolic extract for future ethnopharmacological investigations. |
| first_indexed | 2024-03-12T01:21:23Z |
| format | Article |
| id | doaj.art-4a20027956a1416faee430106c6d8a47 |
| institution | Directory Open Access Journal |
| issn | 1018-3647 |
| language | English |
| last_indexed | 2024-03-12T01:21:23Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of King Saud University: Science |
| spelling | doaj.art-4a20027956a1416faee430106c6d8a472023-09-13T04:24:41ZengElsevierJournal of King Saud University: Science1018-36472023-10-01357102807Neurotoxicity of aluminium chloride and okadaic acid in zebrafish: Insights into Alzheimer's disease models through anxiety and locomotion testing, and acute toxicity assessment with Litsea garciae bark's methanolic extractSiti Zaleha Raduan0Qamar Uddin Ahmed1Abdul Razak Kasmuri2Muhamad Rusdi Ahmad Rusmili3Wan Azizi Wan Sulaiman4Mohd Farooq Shaikh5Muhammad Hamdi Mahmood6Syed Najmul Hejaz Azmi7Mohammad Z. Ahmed8Shadab Kazmi9Department of Basic Medical Sciences, Kulliyyah of Pharmacy, International Islamic University Malaysia (IIUM), 25200 Kuantan, Pahang, Malaysia; Department of Para-clinical Sciences, FMHS, UNIMAS, 94300 Kota Samarahan, Sarawak, MalaysiaDrug Discovery and Synthetic Chemistry Research Group, Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, IIUM, 25200 Kuantan, Pahang, Malaysia; Corresponding author.Department of Basic Medical Sciences, Kulliyyah of Pharmacy, International Islamic University Malaysia (IIUM), 25200 Kuantan, Pahang, MalaysiaDepartment of Basic Medical Sciences, Kulliyyah of Pharmacy, International Islamic University Malaysia (IIUM), 25200 Kuantan, Pahang, MalaysiaUniversity College MAIWP International, 68100, Batu Caves, Kuala Lumpur, MalaysiaNeuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia; School of Dentistry and Medical Sciences, Charles Sturt University, New South Wales, AustraliaDepartment of Basic Medical Sciences, FMHS, UNIMAS, 94300 Kota Samarahan, Sarawak, MalaysiaApplied Sciences Department, College of Applied Sciences and Pharmacy, University of Technology and Applied Sciences-Muscat, P. O. Box 74, Al-Khuwair, 133, OmanDepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Child Health, School of Medicine, University of Missouri, Columbia, MO, USAAlzheimer's disease (AD) is a complicated neurodegenerative disorder that presents significant challenges for the development of effective therapeutic interventions. Understanding disease mechanisms and exploring potential treatments require the use of animal models that accurately replicate the pathology of AD. In this study, we investigated the potential of two neurotoxin inducers, aluminium chloride (AlCl3) and okadaic acid (OKA), to validate the zebrafish as a model organism for AD. AD can impact locomotor activity and induce anxiety-like behaviors. To assess these behaviors, a 6-minute novel tank test was conducted. Zebrafish were administered with low, medium, or high doses of neurotoxic agent (AlCl3 or OKA) intraperitoneally twice weekly for 21 days. Behavioral activities were recorded at three time points: day 7 (short duration), day 14 (moderate duration), and day 21 (extended duration). The behavioral task required the evaluation of four endpoints. Methanolic extract of Litsea garciae bark was selected as a potential plant for the treatment of AD in this study, based on its previously demonstrated antioxidant effect. However, the acute toxicity of this plant has not been previously assessed. Therefore, this research was aimed to investigate the acute toxicity of the L. garciae bark’s methanolic extract in adult zebrafish. The extract was immersed in a static system following OECD Test Guideline No. 203, and the acute toxicity test involved monitoring the adult zebrafish for 96 h for any deaths or apparent abnormalities. Regarding the behavioural task, the groups induced with 100 nM of OKA demonstrated significant differences in all measured parameters compared to the control group at the 21-day time point. In contrast, none of the parameters were significantly different between the AlCl3-induced groups and the control group at any of the three time points (7, 14, or 21 days). Regarding acute toxicity, neither the test group (100 mg/L) nor the control group recorded any deaths or abnormalities. Therefore, no LC50 value could be determined. These findings confirm the acceptance of OKA as an inducer in the zebrafish model of AD and highlight the significance of the safe and non-toxic nature of L. garciae bark's methanolic extract for future ethnopharmacological investigations.http://www.sciencedirect.com/science/article/pii/S1018364723002690Alzheimer's diseaseAdult zebrafishAluminium chlorideOkadaic acidLitsea garciaeAcute toxicity |
| spellingShingle | Siti Zaleha Raduan Qamar Uddin Ahmed Abdul Razak Kasmuri Muhamad Rusdi Ahmad Rusmili Wan Azizi Wan Sulaiman Mohd Farooq Shaikh Muhammad Hamdi Mahmood Syed Najmul Hejaz Azmi Mohammad Z. Ahmed Shadab Kazmi Neurotoxicity of aluminium chloride and okadaic acid in zebrafish: Insights into Alzheimer's disease models through anxiety and locomotion testing, and acute toxicity assessment with Litsea garciae bark's methanolic extract Journal of King Saud University: Science Alzheimer's disease Adult zebrafish Aluminium chloride Okadaic acid Litsea garciae Acute toxicity |
| title | Neurotoxicity of aluminium chloride and okadaic acid in zebrafish: Insights into Alzheimer's disease models through anxiety and locomotion testing, and acute toxicity assessment with Litsea garciae bark's methanolic extract |
| title_full | Neurotoxicity of aluminium chloride and okadaic acid in zebrafish: Insights into Alzheimer's disease models through anxiety and locomotion testing, and acute toxicity assessment with Litsea garciae bark's methanolic extract |
| title_fullStr | Neurotoxicity of aluminium chloride and okadaic acid in zebrafish: Insights into Alzheimer's disease models through anxiety and locomotion testing, and acute toxicity assessment with Litsea garciae bark's methanolic extract |
| title_full_unstemmed | Neurotoxicity of aluminium chloride and okadaic acid in zebrafish: Insights into Alzheimer's disease models through anxiety and locomotion testing, and acute toxicity assessment with Litsea garciae bark's methanolic extract |
| title_short | Neurotoxicity of aluminium chloride and okadaic acid in zebrafish: Insights into Alzheimer's disease models through anxiety and locomotion testing, and acute toxicity assessment with Litsea garciae bark's methanolic extract |
| title_sort | neurotoxicity of aluminium chloride and okadaic acid in zebrafish insights into alzheimer s disease models through anxiety and locomotion testing and acute toxicity assessment with litsea garciae bark s methanolic extract |
| topic | Alzheimer's disease Adult zebrafish Aluminium chloride Okadaic acid Litsea garciae Acute toxicity |
| url | http://www.sciencedirect.com/science/article/pii/S1018364723002690 |
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