Toxicity effects of curcumin analogue, 2, 6-BIS (2-fluorobenzylidene) cyclohexanone on zebrafish (Danio rerio F. Hamilton, 1822)

Non-steroidal anti-inflammatory drugs (NSAIDs) have been used to reduce pain and treat inflammatory diseases such as Rheumatoid Arthritis and Alzhemeir’s Disease. However, treatment with NSAIDs has been associated with significance side effects towards heart diseases in humans and experimental...

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Main Author: Nazarudin, Nur Amiza
Format: Thesis
Language:English
Published: 2017
Subjects:
Online Access:http://psasir.upm.edu.my/id/eprint/90374/
http://psasir.upm.edu.my/id/eprint/90374/1/FBSB%202019%2027%20ir.pdf
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author Nazarudin, Nur Amiza
author_facet Nazarudin, Nur Amiza
author_sort Nazarudin, Nur Amiza
building UPM Institutional Repository
collection Online Access
description Non-steroidal anti-inflammatory drugs (NSAIDs) have been used to reduce pain and treat inflammatory diseases such as Rheumatoid Arthritis and Alzhemeir’s Disease. However, treatment with NSAIDs has been associated with significance side effects towards heart diseases in humans and experimental animals in long terms. Our previous study has shown that curcumin analogue, 2,6-bis(2- fluorobenzylidene)cyclohexanone (MS65) demonstrated strong anti-inflammatory activity in cellular model. Thus, in the present study the toxicity effects of newly synthesized curcumin analogue (MS65) was determined on zebrafish (Danio rerio) as an animal model. The toxicity effects of MS65 compound were evaluated by measuring survival rate and recording heartbeat of zebrafish embryos from day 0 to day 5, observing the morphological defects in developing zebrafish embryos, investigating the cardiac defects on 72 hours postfertilization of zebrafish larvae via fluorescence immunostaining and observing the toxicity effects on adult zebrafish kidney and intestine via histopathology. The toxicity effects of curcumin, celecoxib and aristolochic acid (AA) were also carried out for comparison. The LC50 value of survival rate for MS65 compound on zebrafish embryos were 12.5 µM. The heart rate of zebrafish larvae recorded at 5 day of exposure to 6.25 µM of MS65 was 131 ± 0.15 min-1 . The morphological defect result showed pericardial edema toward zebrafish embryos after treated with 6.25 µM of MS65. MF20 Monoclonal antibody stained uniformly in the heart of MS65- treated zebrafish larvae and showed normal size of the heart. In contrast, MF20 staining in AA-treated zebrafish larvae showed a more intense pattern and highlighted the small size of the heart. Histological analysis reveals that MS65-treated adult zebrafish displayed less necrosis in kidney and low level of erosion in intestine. The results demonstrated that MS65 compound showed low toxicity effects toward zebrafish model compared to celecoxib, an NSAID and AA, a toxic compound that caused heart failure in zebrafish embryos. As a conclusion, the ii present study indicated that the newly synthesized curcumin analogue, MS65 has low toxicity effects towards zebrafish model and could be pharmacologic potential drug in the treatment of diseases with low toxicity effects.
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spelling upm-903742021-12-01T03:20:47Z http://psasir.upm.edu.my/id/eprint/90374/ Toxicity effects of curcumin analogue, 2, 6-BIS (2-fluorobenzylidene) cyclohexanone on zebrafish (Danio rerio F. Hamilton, 1822) Nazarudin, Nur Amiza Non-steroidal anti-inflammatory drugs (NSAIDs) have been used to reduce pain and treat inflammatory diseases such as Rheumatoid Arthritis and Alzhemeir’s Disease. However, treatment with NSAIDs has been associated with significance side effects towards heart diseases in humans and experimental animals in long terms. Our previous study has shown that curcumin analogue, 2,6-bis(2- fluorobenzylidene)cyclohexanone (MS65) demonstrated strong anti-inflammatory activity in cellular model. Thus, in the present study the toxicity effects of newly synthesized curcumin analogue (MS65) was determined on zebrafish (Danio rerio) as an animal model. The toxicity effects of MS65 compound were evaluated by measuring survival rate and recording heartbeat of zebrafish embryos from day 0 to day 5, observing the morphological defects in developing zebrafish embryos, investigating the cardiac defects on 72 hours postfertilization of zebrafish larvae via fluorescence immunostaining and observing the toxicity effects on adult zebrafish kidney and intestine via histopathology. The toxicity effects of curcumin, celecoxib and aristolochic acid (AA) were also carried out for comparison. The LC50 value of survival rate for MS65 compound on zebrafish embryos were 12.5 µM. The heart rate of zebrafish larvae recorded at 5 day of exposure to 6.25 µM of MS65 was 131 ± 0.15 min-1 . The morphological defect result showed pericardial edema toward zebrafish embryos after treated with 6.25 µM of MS65. MF20 Monoclonal antibody stained uniformly in the heart of MS65- treated zebrafish larvae and showed normal size of the heart. In contrast, MF20 staining in AA-treated zebrafish larvae showed a more intense pattern and highlighted the small size of the heart. Histological analysis reveals that MS65-treated adult zebrafish displayed less necrosis in kidney and low level of erosion in intestine. The results demonstrated that MS65 compound showed low toxicity effects toward zebrafish model compared to celecoxib, an NSAID and AA, a toxic compound that caused heart failure in zebrafish embryos. As a conclusion, the ii present study indicated that the newly synthesized curcumin analogue, MS65 has low toxicity effects towards zebrafish model and could be pharmacologic potential drug in the treatment of diseases with low toxicity effects. 2017-04 Thesis NonPeerReviewed text en http://psasir.upm.edu.my/id/eprint/90374/1/FBSB%202019%2027%20ir.pdf Nazarudin, Nur Amiza (2017) Toxicity effects of curcumin analogue, 2, 6-BIS (2-fluorobenzylidene) cyclohexanone on zebrafish (Danio rerio F. Hamilton, 1822). Masters thesis, Universiti Putra Malaysia. Cyclooxygenases Fish as laboratory animals Animal models in research
spellingShingle Cyclooxygenases
Fish as laboratory animals
Animal models in research
Nazarudin, Nur Amiza
Toxicity effects of curcumin analogue, 2, 6-BIS (2-fluorobenzylidene) cyclohexanone on zebrafish (Danio rerio F. Hamilton, 1822)
title Toxicity effects of curcumin analogue, 2, 6-BIS (2-fluorobenzylidene) cyclohexanone on zebrafish (Danio rerio F. Hamilton, 1822)
title_full Toxicity effects of curcumin analogue, 2, 6-BIS (2-fluorobenzylidene) cyclohexanone on zebrafish (Danio rerio F. Hamilton, 1822)
title_fullStr Toxicity effects of curcumin analogue, 2, 6-BIS (2-fluorobenzylidene) cyclohexanone on zebrafish (Danio rerio F. Hamilton, 1822)
title_full_unstemmed Toxicity effects of curcumin analogue, 2, 6-BIS (2-fluorobenzylidene) cyclohexanone on zebrafish (Danio rerio F. Hamilton, 1822)
title_short Toxicity effects of curcumin analogue, 2, 6-BIS (2-fluorobenzylidene) cyclohexanone on zebrafish (Danio rerio F. Hamilton, 1822)
title_sort toxicity effects of curcumin analogue, 2, 6-bis (2-fluorobenzylidene) cyclohexanone on zebrafish (danio rerio f. hamilton, 1822)
topic Cyclooxygenases
Fish as laboratory animals
Animal models in research
url http://psasir.upm.edu.my/id/eprint/90374/
http://psasir.upm.edu.my/id/eprint/90374/1/FBSB%202019%2027%20ir.pdf