| Residential College | true |
| Status | 即將出版Forthcoming |
| Artemisinin protected human retinal pigment epithelial cells from Amiodarone-induced oxidative damage via CaMKK2/AMPK/Nrf2 signaling pathway | |
Chao Yang; ZHENG WENHUA 
| |
| 2024-08 | |
| Conference Name | The 12th Annual Meeting of The Good Practice in Traditional Chinese Medicine Research Association |
| Conference Date | 2024-08-24-26 |
| Conference Place | Regency Art Hotel, Macau SAR, China |
| Abstract | Severe side effects limit the clinical use of Amiodarone, a highly effective antiarrhythmic drug, one of side effects is the ocular toxicity. This study aimed to evaluate the protective effect of the antimalarial drug Artemisinin against Amiodarone-induced oxidative injury in human retinal pigment epithelium (RPE) cells. Our findings reveal that Artemisinin pretreatment attenuated cell viability decline, lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) decrease induced by Amiodarone in D407 cells. Artemisinin suppressed the Amiodarone-induced upregulation of proapoptotic cleaved caspase 3 and cleaved Poly (ADP-ribose) polymerase (PARP) protein levels in D407 cells. Artemisinin also upregulated the phosphorylated- Adenosine monophosphate-activated protein kinase ɑ (AMPKɑ) (p-AMPK) level, and Calcium/Calmodulin Dependent Protein Kinase Kinase 2 (CaMKK2) and nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels in D407 cells. The AMPK inhibitor (Compound C), CaMKK2 inhibitor (STO-609), and Nrf2 inhibitor (ML385) blocked the protection of Artemisinin against cell viability decline or LDH release induced by Amiodarone. Compound C and STO-609 also inhibited Artemisinin-induced upregulation of Nrf2 downstream antioxidant HO-1 protein level and downregulation of cleaved caspase 3 protein level. AMPK activator AICAR or AMPKɑ overexpression protected D407 cells from cell viability decline or LDH release induced by Amiodarone. The knockdown of Nrf2 induced the downregulation of downstream HO-1 protein level and blocked the protection of Artemisinin against Amiodarone-induced LDH release. The knockdown of AMPKɑ induced the downregulation of HO-1 protein level and upregulation of cleaved caspase 3 protein level in D407 cells. The protection of Artemisinin was also proved in ARPE19 cells and primary human RPE cells. Furthermore, in vivo, Artemisinin prevented the Amiodarone-induced decrease of photopic 3.0 electroretinography (ERG) a- and b-wave amplitudes and improved Amiodarone-induced detachment of pigment epithelium and apoptosis of photoreceptor cells in the retina of mice. The protection of Artemisinin against Amiodarone-induced retinal injury was inhibited by Compound C. Our results demonstrate that Artemisinin has important potential in the prevention of Amiodarone-induced ocular toxicity. |
| Other Abstract | This research was supported by National Natural Science Foundation of China (32070969), The Science and Technology Development Fund, Macau SAR (File No. 0104/2022/A2, 0038/2020/AMJ, 0127/2019/A3 and 0044/2019/AGJ), The Guangdong Provincial Funding Committee (GPSC) for Basic and Applied Fundamental Research (2022-Natural Science Foundation, EF019/FHS-ZWH/2022/GDSTC), GPSC Guangdong-Hong Kong-Macao Joint Laboratory for New drug screening (EF2023-00054-FHS), University of Macau (File No. MYRG2020-00158-FSH, MYRG-GRG2023-00118-FHS-UMDF, and MYRG2022-00154-FHS). |
| Keyword | Artemisinin Amiodarone Human Retinal Pigment Epithelium Cells Oxidative Damage Ampk |
| Document Type | Conference paper |
| Collection | DEPARTMENT OF PHARMACEUTICAL SCIENCES |
| Corresponding Author | ZHENG WENHUA |
| Recommended Citation GB/T 7714 | Chao Yang,ZHENG WENHUA. Artemisinin protected human retinal pigment epithelial cells from Amiodarone-induced oxidative damage via CaMKK2/AMPK/Nrf2 signaling pathway[C], 2024. |
| APA | Chao Yang., & ZHENG WENHUA (2024). Artemisinin protected human retinal pigment epithelial cells from Amiodarone-induced oxidative damage via CaMKK2/AMPK/Nrf2 signaling pathway. . |
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