Radioprotective effect of mistletoe extract on intestinal toxicity: in vivo study using adult zebrafish

Abstract

Purpose

The intestine is a dose-limiting organ in the treatment of intra-abdominal cancer. We previously reported that the extract of mistletoe parasites on Quercus had a more potent radioprotective effect than amifostine in reducing the developmental toxicities of zebrafish embryos. In this study, radioprotection against intestinal toxicity was investigated in adult zebrafish.

Methods

Wild-type adult AB zebrafish were exposed to 45–50 Gy of photon beam irradiation and/or treated with mistletoe extract orally 1 h before. The main endpoints of the study were survival and degree of deformation of the intestinal villi.

Results

The median follow-up period was 10 d post-irradiation (range: 7–11 d). A total of 105 zebrafish were used, including 42 in the radiation alone, 42 in the radiation and mistletoe arms, and 21 control subjects (mistletoe alone, mock-irradiated arm). The rate of both significant deformity and death was 53% in the radiation-alone arm, whereas the corresponding rate was 30% in the radiation and mistletoe arms. Significant deformity-free survival rates at 10 d post-irradiation in the radiation alone, and radiation and mistletoe arms were 44.7% (95% confidence interval [CI]:20–54.3) and 68.4% (95% CI:53.8–86.8), respectively (p=.046). The radiation and mistletoe arms showed decreased expression of two of three inflammatory genes (IL-1β and IL-6) compared to the radiation alone group (p<.05).

Conclusion

The radioprotective effect against intestinal toxicity was successfully shown in an adult zebrafish model. This result suggests the possibility of clinical use of mistletoe extract for the treatment of abdominal cancers.

Keywords:

• Zebrafish
• radiotherapy
• radioprotectant
• mistletoe

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available upon request from the corresponding author, CHR.

Additional information

Funding

This study was supported by the National Research Fund of Korea (NRF-2019M2D2A1A01031560).

Notes on contributors

Sunmin Park

Sunmin Park is a radiation oncology specialist in the Korea University Ansan Hospital. She performed drafting of the manuscript and experiments of external radiation.

Suhyun Kim

Suhyun Kim performed experiments and management of zebrafishes, and edited the manuscript.

Soonil Koun

Soonil Koun performed experiments and management of zebrafishes.

Hae-Chul Park

Hae-Chul Park is head of the zebrafish research lab of Korea University Ansan Hospital. He supervised the research and present study, and shared his expertise.

Won Sup Yoon

Won Sup Yoon is director of the Radiation Oncology Department of Korea University Ansan Hospital. He supervised the research and present study, and shared his expertise.

Chai Hong Rim

Chai Hong Rim directed experiments, drafting and statistical analyses. He has published more than 60 articles with subjects of meta-analyses, cancer prevention, and in vivo studies using a zebrafish model, in recent 5 years.