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Drug Chem Toxicol. 2019 Oct 28:1-8. doi: 10.1080/01480545.2019.1663865. [Epub ahead of print]

Induction of developmental toxicity and cardiotoxicity in zebrafish embryos/larvae by acetyl-11-keto-β-boswellic acid (AKBA) through oxidative stress.

Author information

1
Biology Institute, Qilu University of Technology (Shandong Academy of Sciences) , Jinan , People's Republic of China.
2
Biological Science Section, Therapeutic Good Administration , Symonston , Australia.
3
Tianjin Center for New Drug Evaluation and Research, State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research , Tianjin , People's Republic of China.

Abstract

Acetyl-11-keto-β-boswellic acid (AKBA), a triterpenoid from Boswellia serrate, is regarded as an angiogenesis inhibitor. However, its toxicity is unknown. The aim of this study was to examine its developmental toxicity and cardiotoxicity. A developmental toxicity assay in zebrafish embryos/larvae from 4 to 96 hours post-fertilization (hpf) was performed and a cardiotoxicity assay was designed from 48 to 72 hpf. Markers of oxidative stress and related genes were selected to access the possible mechanisms. According to the results, AKBA induced pericardium edema, yolk-sac edema, abnormal melanin, spinal curvature, hatching inhibition and shortened body length. Further, increased SV-BA distance, reduced heart rate, increased pericardium area and decreased blood flow velocity were detected in AKBA treated groups. The inhibition of cardiac progenitor gene expression, such as Nkx2.5 and Gata4, may be related to cardiotoxicity. The activities of antioxidant enzymes were decreased and the content of MDA was increased. In addition, AKBA treatment decreased the expression levels of Mn-Sod, Cat, and Gpx. These results suggested that AKBA induced developmental toxicity and cardiotoxicity through oxidative stress. As far as we know, this is the first report on the toxicity of AKBA. It reminds us to pay attention to developmental toxicity and cardiotoxicity of AKBA.

KEYWORDS:

Acetyl-11-keto-β-boswellic acid; cardiotoxicity; developmental toxicity; oxidative stress; zebrafish

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