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- Title
Rapamycin reduces mortality in acute-stage paraquat-induced toxicity in zebrafish.
- Authors
Nan Feng; Zhaolian Bian; Xiaobin Zhang; Changsheng Wang; Jie Chen; Feng, Nan; Bian, Zhaolian; Zhang, Xiaobin; Wang, Changsheng; Chen, Jie
- Abstract
<bold>Introduction: </bold>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.<bold>Methods: </bold>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).<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
RAPAMYCIN; MORTALITY; THERAPEUTICS; BRACHYDANIO; ANIMALS; BIOLOGICAL models; FISHES; PYRIDINE; ACUTE diseases; PHARMACODYNAMICS
- Publication
Singapore Medical Journal, 2019, Vol 60, Issue 5, p241
- ISSN
0037-5675
- Publication type
journal article
- DOI
10.11622/smedj.2018132