A developmental toxicity assay of Carpesii Fructus on zebrafish embryos/larvae

Abstract

Carpesii Fructus, the dried fruit of Carpesium abrotanoides L., has been used as a traditional Chinese medicine for centuries to kill intestinal parasites in children. It has been recorded as a mildly toxic medicine in the Chinese pharmacopoeia. However, little proof of its toxicology has been reported in modern pharmacology. This study investigated for the first time its developmental toxicity on zebrafish embryos/larvae from 6 to 96 h post-fertilization (hpf). In addition, the enzymes and genes associated with oxidative stress and apoptosis were tested to investigate the potential toxicologic mechanism preliminarily. The observation of toxicologic endpoints showed the developmental toxicity of Carpesii Fructus. Pericardial edema, yolk sac edema, bleeding tendency, and enlarged yolk were the most commonly occurring morphological changes observed in our study. According to the results of acridine orange staining and morphological observation, the developing heart was speculated to be the target organ of toxicity. Furthermore, Carpesii Fructus exposure changed the activities of defense enzymes, increased malondialdehyde (MDA) content, decreased caspase-3 activity, and altered mRNA levels of related genes (ogg1, p53, Cu/Zn-Sod, Mn-Sod, and Cat↓; Gpx↑) in zebrafish larvae, indicating that oxidative stress and additional apoptosis should have roles in the developmental toxicity of Carpesii Fructus. This is the first study that provides proof of modern pharmacology on the teratogenicity and possible toxicologic mechanism of Carpesii Fructus.