2. Academic Validation
  3. Minocycline attenuates the bilirubin-induced developmental neurotoxicity through the regulation of innate immunity and oxidative stress in zebrafish embryos

Minocycline attenuates the bilirubin-induced developmental neurotoxicity through the regulation of innate immunity and oxidative stress in zebrafish embryos

  • Toxicol Appl Pharmacol. 2024 Feb 9:484:116859. doi: 10.1016/j.taap.2024.116859.
Guanghua Xiong 1,  Tianle Hu 1,  Yihong Yang 2,  Haiyan Zhang 1,  Meiling Han 1,  Jiahao Wang 1,  Yipeng Jing 1,  Hongbo Liu 3,  Xinjun Liao 4,  Yong Liu 5
Affiliations

Affiliations

  • 1 College of Biology and Food Engineering, Key Laboratory of Embryo Development and Reproductive Regulation of Anhui Province, Fuyang Normal University, Fuyang 236041, Anhui, China.
  • 2 Emergency Department of Fuyang People's Hospital, Fuyang 236000, Anhui, China.
  • 3 Emergency Department of Fuyang People's Hospital, Fuyang 236000, Anhui, China. Electronic address: [email protected].
  • 4 College of Life Sciences, Jinggangshan University, Ji'an 343009, Jiangxi, China. Electronic address: [email protected].
  • 5 College of Biology and Food Engineering, Key Laboratory of Embryo Development and Reproductive Regulation of Anhui Province, Fuyang Normal University, Fuyang 236041, Anhui, China. Electronic address: [email protected].
PMID: 38342443 DOI: 10.1016/j.taap.2024.116859
Abstract

When liver or intestinal function is impaired, bilirubin accumulates in the body and leads to neonatal jaundice. However, the potential negative effects caused by excessive accumulation of bilirubin such as developmental immunotoxicity and neurotoxicity remain unclear. We used a zebrafish model to establish bilirubin-induced jaundice symptoms and evaluated the toxic effects of bilirubin in aquatic organisms. Firstly, our results suggested that bilirubin exposure markedly decreased the survival rate, induced the developmental toxicity and increased the yellow pigment deposited in the zebrafish tail. Meanwhile, the number of macrophages and neutrophils was substantially reduced in a concentration-dependent manner. Besides, the antioxidant Enzyme activities were greatly elevated while the inflammatory genes were significantly decreased after bilirubin exposure. Secondly, transcriptome analysis identified 708 genes were differentially expressed after bilirubin exposure, which animal organ morphogenesis, chemical synaptic transmission, and MAPK / mTOR signaling pathways were significantly enriched. Thirdly, bilirubin exposure leads to a significant decrease in the motility of zebrafish, including a dose-dependent decrease in the travelled distance, movement time, and average velocity. Moreover, the innate immune genes and apoptosis-related genes such as TLR4, NF-κB p65, STAT3 and p53 were elevated at a concentration of 10 μg/mL of bilirubin. Finally, our results further revealed that the anti-inflammatory and neuroprotective minocycline could partially rescue the bilirubin-induced neurobehavioral disorders in zebrafish embryos. In conclusion, our study explored the bilirubin-induced immunotoxicity and neurotoxicity in aquatic organisms, which will provide a theoretical basis for the treatment of neonatal jaundice in clinical practice.

Keywords

Bilirubin; Immunotoxicity; Neonatal jaundice; Neurobehavioral disorder; Zebrafish.

Figures
Products