Staff View: 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

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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Main Authors:	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
Format:	Article
Language:	English
Published:	Elsevier B.V. 2023
Subjects:	Q Science (General) RM Therapeutics. Pharmacology
Online Access:	http://ir.unimas.my/id/eprint/42446/3/Neurotoxicity.pdf http://ir.unimas.my/id/eprint/42446/ https://www.sciencedirect.com/science/article/pii/S1018364723002690 https://doi.org/10.1016/j.jksus.2023.102807
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id	my.unimas.ir.42446
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spelling	my.unimas.ir.424462023-07-27T02:51:59Z http://ir.unimas.my/id/eprint/42446/ 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 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 Q Science (General) RM Therapeutics. Pharmacology 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. Elsevier B.V. 2023-07-20 Article PeerReviewed text en http://ir.unimas.my/id/eprint/42446/3/Neurotoxicity.pdf Siti Zaleha, Raduan and Qamar Uddin, Ahmed and Abdul Razak, Kasmuri and Muhamad Rusdi, Ahmad Rusmili and Wan Azizi, Wan Sulaiman and Mohd Farooq, Shaikh and Muhammad Hamdi, Mahmood and Syed Najmul, Hejaz Azmi and Mohammad Z., Ahmed and Shadab, Kazmi (2023) 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, 35 (7). pp. 1-9. ISSN 1018-3647 https://www.sciencedirect.com/science/article/pii/S1018364723002690 https://doi.org/10.1016/j.jksus.2023.102807
institution	Universiti Malaysia Sarawak
building	Centre for Academic Information Services (CAIS)
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaysia Sarawak
content_source	UNIMAS Institutional Repository
url_provider	http://ir.unimas.my/
language	English
topic	Q Science (General) RM Therapeutics. Pharmacology
spellingShingle	Q Science (General) RM Therapeutics. Pharmacology 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
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.
format	Article
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
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_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_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_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
publisher	Elsevier B.V.
publishDate	2023
url	http://ir.unimas.my/id/eprint/42446/3/Neurotoxicity.pdf http://ir.unimas.my/id/eprint/42446/ https://www.sciencedirect.com/science/article/pii/S1018364723002690 https://doi.org/10.1016/j.jksus.2023.102807
_version_	1772816325386698752
score	13.211869

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

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