Protective role of Bu-Zhong-Yi-Qi decoction on aristolochic acid-intoxicated zebrafish

Purpose: To investigate the potential nephroprotective effects of a traditional Chinese medical prescription, Bu-Zhong-Yi-Qi Decoction (BZYQD) in an aristolochic acid (AA)-intoxicated zebrafish model. Methods: A green fluorescent zebrafish line Tg (wt1b:EGFP) was used, and different exposure protocols were applied. Once a suitable protective concentration of BZYQD was found, antibody staining and real-time PCR methods were applied and the pro-inflammatory gene expressions were determined. Results: The results showed that low dose (10 ppm) of BZYQD attenuates the AA-induced malformed kidney phenotype. This finding was further substantiated by an examination of the integrity of pronephric tubes in the treated embryos. Pre-treatment with BZYQD suppressed the elevated expressions of pro-inflammatory genes, including tumor necrosis factor-α and myeloperoxidase, induced by AA exposure (1.6 ~ 2.3-fold). This indicates that the nephroprotective effect of BZYQD may be mediated by suppression of pro-inflammatory gene expression. On the other hand, a high dose (500 ppm) of BZYQD caused nephrotoxic effect. Conclusion: An efficient model to identify AA-protective compounds using zebrafish embryos has been successfully established. Using this strategy, it has been found that BZYQD is nephroprotective in zebrafish embryos, and might have the potential to be applied in humans.