Oxidative stress induced antioxidant and neurotoxicity demonstrated in vivo zebrafish embryo or larval model and their normalization due to morin showing therapeutic implications

Abstract

Aims: The study examined that morin as possible antioxidant and neuroprotective due to oxidative stress (H₂O₂) in zebrafish larval model.

Materials and methods: Zebrafish larvae were induced with oxidative stress using H₂O₂ at 1 mM; their behavioural changes were assessed through partition preference and horizontal compartment test. The head section without eyes and yolk sac of zebrafish larvae were employed for enzyme assays such as SOD, CAT, Thiobarbituric acid reactive substances assay, reduced glutathione, glutathione peroxidase activity, glutathione S transferase, Acetylcholinesterase activity and nitrate levels. Also, intracellular ROS and apoptosis in larval head was detected by DCFDA and acridine orange staining followed by gene expression studies.

Key findings: Morin exposure was not harmful to the larvae at concentration between 20 and 60 μM, but it caused non-lethal deformity between 80 and 100 μM. In the partition test, zebrafish embryos treated with H₂O₂ showed cognitive impairment, whereas the morin-treated groups showed an improved behavioural activity. The study also found that restoring antioxidant enzymes and reduced lipid peroxidation which had a neuroprotective impact. Inhibition of NO overproduction and increased AChE activity were also shown to reduce the neuronal damage. Apoptosis and intracellular ROS levels were reduced in larvae when it was co-incubated with morin. Morin treatment up regulated the antioxidant enzymes against oxidative stress.

Significance: Morin provides protection against H₂O₂ induced oxidative stress through a cellular antioxidant defence mechanism by up-regulating gene expression, thus increasing the antioxidant activity at cellular or organismal stage.

Keywords: Antioxidant; Morin; Neuroprotection; Oxidative stress; Zebrafish model.