PUBLICATION
Morphine Ameliorates Pentylenetetrazole-Induced Locomotor Pattern in Zebrafish Embryos; Mechanism Involving Regulation of Opioid Receptors, Suppression of Oxidative stress and Inflammation in Epileptogenesis
- Authors
- Üstündağ, F.D., Ünal, İ., Üstündağ, Ü.V., Cansız, D., Beler, M., Alturfan, A.A., Tiber, P.M., Emekli-Alturfan, E.
- ID
- ZDB-PUB-220723-5
- Date
- 2022
- Source
- Toxicology mechanisms and methods 33(2): 151-160 (Journal)
- Registered Authors
- Beler, Merih, Emekli-Alturfan, Ebru, Üstündağ, Ünsal Veli
- Keywords
- Pentylenetetrazole, morphine, oxidant-antioxidant, valproic acid, zebrafish embryos
- MeSH Terms
-
- Acetylcholinesterase
- Animals
- Anticonvulsants/therapeutic use
- Antioxidants/metabolism
- Brain-Derived Neurotrophic Factor
- Epilepsy*/chemically induced
- Epilepsy*/drug therapy
- Inflammation
- Morphine*/therapeutic use
- Oxidative Stress
- Pentylenetetrazole*/toxicity
- Receptors, Opioid/genetics
- Seizures/chemically induced
- Seizures/drug therapy
- Valproic Acid/therapeutic use
- Zebrafish
- PubMed
- 35866229 Full text @ Toxicol. Mech. Methods
- CTD
- 35866229
Citation
Üstündağ, F.D., Ünal, İ., Üstündağ, Ü.V., Cansız, D., Beler, M., Alturfan, A.A., Tiber, P.M., Emekli-Alturfan, E. (2022) Morphine Ameliorates Pentylenetetrazole-Induced Locomotor Pattern in Zebrafish Embryos; Mechanism Involving Regulation of Opioid Receptors, Suppression of Oxidative stress and Inflammation in Epileptogenesis. Toxicology mechanisms and methods. 33(2):151-160.
Abstract
Zebrafish (Danio rerio) is becoming an increasingly important model in epilepsy research. Pentylenetetrazole (PTZ) is a convulsant agent that induces epileptic seizure-like state in zebrafish and zebrafish embryos and is most commonly used in antiepileptic drug discovery research to evaluate seizure mechanisms. Classical antiepileptic drugs such as valproic acid (VPA) reduce PTZ-induced epileptiform activities. Opioid system has been suggested to play a role in epileptogenesis. The aim of our study is to determine the effects of morphine in PTZ-induced epilepsy model in zebrafish embryos by evaluating locomotor activity and parameters related with oxidant-antioxidant status, inflammation, and cholinergic system as well as markers of neuronal activity c-fos, bdnf and opioid receptors. Zebrafish embryos at 72 hpf were exposed to PTZ (20 mM), VPA (1mM) and, Morphine (MOR) (100 µM). MOR and VPA pre-treated groups were treated with either MOR (MOR + PTZ) or VPA (VPA + PTZ) for 20 minutes before PTZ expoure. Locomotor activity was quantified as total distance moved (mm), average speed (mm/sec) and exploration rate (%) and analyzed using ToxTrac tracking programme. Oxidant-antioxidant system parameters, acetylcholinesterase activity and sialic acid leves were evaluated using spectrophotometric methods. The expression of c-fos, bdnf, oprm1 and oprd1 were evaluated by RT-PCR. MOR pre-treatment ameliorated PTZ-induced locomotor pattern as evidenced by improved average speed, exploration rate and distance travelled. We report the restoration of inflammatory and oxidant-antioxidant system parameters, c-fos, bdnf and opioid receptor oprm1 as the possible mechanisms involved in the ameliorative effect of MOR against PTZ-induced epileptogenic process in zebrafish embryos.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping