PMID- 36725266 OWN - NLM STAT- MEDLINE DCOM- 20230203 LR - 20230203 IS - 1001-5302 (Print) IS - 1001-5302 (Linking) VI - 48 IP - 1 DP - 2023 Jan TI - [Hepatotoxicity and mechanism of Rhododendri Mollis Flos based on zebrafish model]. PG - 140-147 LID - 10.19540/j.cnki.cjcmm.20220914.401 [doi] AB - This study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 mug.mL~(-1) of the absolute lethal concentration and 448 mug.mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis. FAU - Chen, Mei-Lin AU - Chen ML AD - Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, School of Chinese Materia Medica,Beijing University of Chinese Medicine Beijing 102488, China. FAU - Li, Zhi-Qi AU - Li ZQ AD - Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, School of Chinese Materia Medica,Beijing University of Chinese Medicine Beijing 102488, China. FAU - Fan, Qi-Qi AU - Fan QQ AD - Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, School of Chinese Materia Medica,Beijing University of Chinese Medicine Beijing 102488, China. FAU - Guo, Si-Min AU - Guo SM AD - Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, School of Chinese Materia Medica,Beijing University of Chinese Medicine Beijing 102488, China. FAU - Cai, Qiong AU - Cai Q AD - Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, School of Chinese Materia Medica,Beijing University of Chinese Medicine Beijing 102488, China. FAU - Lin, Rui-Chao AU - Lin RC AD - Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, School of Chinese Materia Medica,Beijing University of Chinese Medicine Beijing 102488, China. FAU - Wu, Jia-Rui AU - Wu JR AD - Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, School of Chinese Materia Medica,Beijing University of Chinese Medicine Beijing 102488, China. FAU - Zhao, Chong-Jun AU - Zhao CJ AD - Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, School of Chinese Materia Medica,Beijing University of Chinese Medicine Beijing 102488, China. LA - chi PT - English Abstract PT - Journal Article PL - China TA - Zhongguo Zhong Yao Za Zhi JT - Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica JID - 8913656 SB - IM MH - Animals MH - *Zebrafish/genetics MH - Apoptosis MH - Larva MH - *Chemical and Drug Induced Liver Injury OTO - NOTNLM OT - Rhododendri Mollis Flos OT - apoptosis OT - hepatotoxicity OT - zebrafish EDAT- 2023/02/02 06:00 MHDA- 2023/02/04 06:00 CRDT- 2023/02/01 21:03 PHST- 2023/02/01 21:03 [entrez] PHST- 2023/02/02 06:00 [pubmed] PHST- 2023/02/04 06:00 [medline] AID - 10.19540/j.cnki.cjcmm.20220914.401 [doi] PST - ppublish SO - Zhongguo Zhong Yao Za Zhi. 2023 Jan;48(1):140-147. doi: 10.19540/j.cnki.cjcmm.20220914.401.