PUBLICATION
Rapamycin reduces mortality in acute-stage paraquat-induced toxicity in zebrafish
- Authors
- Feng, N., Bian, Z., Zhang, X., Wang, C., Chen, J.
- ID
- ZDB-PUB-181108-7
- Date
- 2018
- Source
- Singapore medical journal 60(5): 241-246 (Journal)
- Registered Authors
- Keywords
- paraquat-induced toxicity, rapamycin, zebrafish
- MeSH Terms
-
- Acute Disease
- Animals
- Disease Models, Animal*
- Paraquat/poisoning*
- Sirolimus/pharmacology*
- Survival Rate
- Zebrafish
- PubMed
- 30402654 Full text @ Singapore Med J
Citation
Feng, N., Bian, Z., Zhang, X., Wang, C., Chen, J. (2018) Rapamycin reduces mortality in acute-stage paraquat-induced toxicity in zebrafish. Singapore medical journal. 60(5):241-246.
Abstract
Introduction Paraquat (PQ) intoxication is frequently associated with a high mortality rate. No specific treatment has been shown to reduce mortality in victims within the first 72 hours. We investigated the protective effects of rapamycin (Rapa) against PQ-induced toxicity in a zebrafish model.
Methods To determine the maximum nonlethal concentration (MNLC) and lethal concentration 50 (LC50) of Rapa, zebrafish were treated at 2-5 days post fertilisation (dpf) and their mortality was recorded every 24 hours. At 5 dpf, the zebrafish were treated with PQ 100 μg/mL or PQ+Rapa (MNLC, 1/3 MNLC or 1/9 MNLC) for 72 hours, and the rate of survival was recorded every 24 hours. Reverse transcription-polymerase chain reaction was used to test the signalling pathway of mTOR (mammalian target of rapamycin).
Results MNLC and LC50 of Rapa were determined to be 6.7 μg/mL and 28.9 μg/mL, respectively. At 48 hours, the PQ+Rapa groups had much lower mortality than the PQ group. The rates of survival of the PQ+Rapa groups were 43.33% (MNLC), 53.89% (1/3 MNLC) and 44.45% (1/9 MLNC), as compared to 19.45% in the PQ group, with the 1/3 MNLC group showing the highest rate of survival (p < 0.001). atg1 was slightly activated in the PQ group. In the PQ+Rapa groups, the expression of atg1 was markedly increased, suggesting strengthening of the autophagy process.
Conclusion Rapa can increase the rate of survival of PQ-intoxicated zebrafish by inhibiting mTOR complex 1 and activating autophagy. Rapa could be an alternative first-line drug in the treatment of PQ poisoning.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping