PUBLICATION
Hydroxyl containing benzo[b]thiophene analogs mitigates the acrylamide induced oxidative stress in the zebrafish larvae by stabilizing the glutathione redox cycle
- Authors
- Hari Deva Muthu, B., Manjunathan, T., Guru, A., Kumar, R.S., Rajakrishnan, R., Kuppusamy, P., Juliet, A., Gopinath, P., Arockiaraj, J.
- ID
- ZDB-PUB-220401-16
- Date
- 2022
- Source
- Life sciences 298: 120507 (Journal)
- Registered Authors
- Keywords
- Acrylamide, Antioxidants, Benzo[b]thiophene, Oxidative stress, Reactive oxygen species
- MeSH Terms
-
- Glutathione/metabolism
- Thiophenes/metabolism
- Thiophenes/pharmacology
- Acrylamide*/toxicity
- Reactive Oxygen Species/metabolism
- Dogs
- Hydroxyl Radical/metabolism
- Oxidative Stress
- Larva
- Zebrafish*
- Antioxidants/metabolism
- Antioxidants/pharmacology
- Animals
- Oxidation-Reduction
- PubMed
- 35358593 Full text @ Life Sci.
Citation
Hari Deva Muthu, B., Manjunathan, T., Guru, A., Kumar, R.S., Rajakrishnan, R., Kuppusamy, P., Juliet, A., Gopinath, P., Arockiaraj, J. (2022) Hydroxyl containing benzo[b]thiophene analogs mitigates the acrylamide induced oxidative stress in the zebrafish larvae by stabilizing the glutathione redox cycle. Life sciences. 298:120507.
Abstract
Aims This study aims to elucidate a systematic free-radical quenching ability of synthesized benzo[b]thiophene derivatives using in vitro assays and acrylamide induced oxidatively stressed model in zebrafish larvae.
Materials and methods Antioxidant activity of the compounds was evaluated using in vitro methods. The toxicity of the compounds was evaluated in Madin-Darby Canine Kidney (MDCK) cell line and zebrafish embryos. Oxidative stress was generated by acrylamide (1 mM) in zebrafish larvae and treated with compounds to evaluate the in vivo antioxidant ability. Specific fluorescence dyes were used to detect ROS generation, lipid peroxidation, and cell death followed by gene expression using RT PCR. Density functional theory (DFT) and in silico pharmacokinetics were also studied.
Key findings Compound BP and EP have a greater in vitro free radical scavenging ability. The maximum tolerated concentration (MTC) of the compounds in zebrafish larvae is 80 μM. The antioxidant system in zebrafish larvae was dysregulated due to acrylamide exposure and improvement was found while treating acrylamide exposed larvae with compounds 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen-2-yl) propan-1-one hydrate (EP). Compound BP and EP enhanced the SOD and CAT activity, reduced the ROS and lipid peroxidation level, thus decreasing cell death in zebrafish larvae. Compound BP and EP also improved the glutathione redox cycle by stabilizing glutathione-related gene expressions.
Significance Hydroxyl-containing compounds BP and EP are promising lead molecules for pathological conditions related to oxidative stress, which showed an attenuated effect on acrylamide-induced oxidative stress in zebrafish larvae by enhancing the glutathione redox cycle and enzymatic antioxidants.
Errata / Notes
This article is corrected by ZDB-PUB-250113-7.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping