PUBLICATION
N-acetylcysteine prevents verapamil-induced cardiotoxicity with no effect on the noradrenergic arch-associated neurons in zebrafish
- Authors
- Gu, Q., Rodgers, J., Robinson, B., Kanungo, J.
- ID
- ZDB-PUB-200710-14
- Date
- 2020
- Source
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 144: 111559 (Journal)
- Registered Authors
- Keywords
- Cardiotoxicity, N-acetylcysteine, Noradrenergic neuron, Tyrosine hydroxylase, Verapamil, Zebrafish
- MeSH Terms
-
- Acetylcysteine/administration & dosage
- Acetylcysteine/pharmacology*
- Animals
- Antioxidants/administration & dosage
- Antioxidants/pharmacology*
- Calcium Channel Blockers/toxicity*
- Cardiotoxicity/prevention & control*
- Cysteine/metabolism
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Embryonic Development/drug effects
- Heart Rate/drug effects
- Verapamil/toxicity*
- Zebrafish/embryology*
- PubMed
- 32640352 Full text @ Food Chem. Toxicol.
Citation
Gu, Q., Rodgers, J., Robinson, B., Kanungo, J. (2020) N-acetylcysteine prevents verapamil-induced cardiotoxicity with no effect on the noradrenergic arch-associated neurons in zebrafish. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 144:111559.
Abstract
There is a strong association between calcium channel blockers (CCBs) and heart failure. CCB toxicity is very common due to overdose and underlying medical conditions. CCBs also have been shown to affect the nervous system. Recently, we demonstrated that the antioxidant N-acetylcysteine (NAC) prevented ketamine-induced cardiotoxicity, developmental toxicity and neurotoxicity. Functionally, we attributed NAC's beneficial effect to its ability to increase cellular calcium. Here, we hypothesized that if there was an involvement of calcium in NAC's preventative effects on ketamine toxicity, NAC might also ameliorate toxicities induced by verapamil, an L-type CCB used to treat hypertension. Using zebrafish embryos, we show that in the absence of NAC, verapamil (up to 100 μM) dose-dependently reduced heart rate and those effects were prevented by NAC co-treatment. Furthermore, a 2-h treatment with NAC rescued reduction of heart rate induced by pre-treatment of 50 and 100 μM of verapamil for 18 h. Verapamil up to 100 μM and NAC up to 1.5 mM did not have any adverse effects on the expression of tyrosine hydroxylase in the noradrenergic neurons of the arch-associated cluster (AAC) located near the heart. NAC did not change cysteine levels in the embryos suggesting that the beneficial effect of NAC on verapamil toxicity may not involve its antioxidant property. In our search for compounds that can prevent CCB toxicity, this study, for the first time, demonstrates protective effects of NAC against verapamil's adverse effects on the heart.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping