PUBLICATION
Increased leptin-b expression and metalloprotease expression contributed to the pyridoxine-associated toxicity in zebrafish larvae displaying seizure-like behavior
- Authors
- Chen, P.Y., Tsai, Y.W., Yw Chang, A., Hua Chang, H., Hsiao, Y.H., Huang, C.W., Sung, P.S., Chen, B.H., Fu, T.F.
- ID
- ZDB-PUB-201021-16
- Date
- 2020
- Source
- Biochemical pharmacology 182: 114294 (Journal)
- Registered Authors
- Keywords
- Epilepsy, Leptin-b, Metalloprotease, Necroptosis, Vitamin B6
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Dose-Response Relationship, Drug
- Gene Expression Regulation, Enzymologic
- Gene Knockdown Techniques
- Larva/drug effects
- Larva/genetics
- Larva/metabolism*
- Metalloproteases/biosynthesis*
- Metalloproteases/genetics
- Pyridoxine/toxicity*
- Receptors, Leptin/biosynthesis*
- Receptors, Leptin/genetics
- Seizures/chemically induced*
- Seizures/genetics
- Seizures/metabolism*
- Vitamin B Complex/toxicity
- Zebrafish
- PubMed
- 33080184 Full text @ Biochem. Pharmacol.
Citation
Chen, P.Y., Tsai, Y.W., Yw Chang, A., Hua Chang, H., Hsiao, Y.H., Huang, C.W., Sung, P.S., Chen, B.H., Fu, T.F. (2020) Increased leptin-b expression and metalloprotease expression contributed to the pyridoxine-associated toxicity in zebrafish larvae displaying seizure-like behavior. Biochemical pharmacology. 182:114294.
Abstract
Epilepsy is a common neurological disorder affecting people of all ages, races and ethnic backgrounds world-wide. Vitamin B6 supplementation has been widely used as an adjuvant for treating epilepsy. However, the adverse effects, including nausea and peripheral sensory neuropathy, caused by long-term and high-dose consumption of vitamin B6 have undermined the usefulness of vitamin B6 supplementation, justifying additional experimental scrutiny of vitamin B6-associated toxicity. In the current study, we found that the presence of pyridoxine, the inactive form of B6 vitamer included in most nutrient supplements, increased the mortality of the larvae displaying chemical-induced epilepsy. The expression of leptin-b, one zebrafish ortholog of human leptin, was significantly increased in the larvae displaying seizures. Increased leptin-b expression alleviated larval seizure-like behavior when exposed to epilepsy inducer, but also increased larval mortality in the presence of pyridoxine. Meanwhile, elevated adam17 and mmp13 mRNA level were found in the larvae simultaneously exposed to epilepsy-inducer and pyridoxine. Adding TNF-α inhibitor and mmp13 inhibitor effectively improved the survival of larvae injected with leptin-b mRNA and exposed to pyridoxine subsequently. We conclude that increased leptin-b and metalloprotease expression contributed, at least partly, to the pyridoxine-associated toxicity observed in larvae displaying seizures.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping