Treatment with sodium benzoate leads to malformation of zebrafish larvae

Tsay, H.J., Wang, Y.H., Chen, W.L., Huang, M.Y., and Chen, Y.H.
Neurotoxicology and teratology   29(5): 562-569 (Journal)
Registered Authors
Chen, Yau-Hung, Tsay, Huey-Jen
Acetyl-choline receptor, Embryonic development, Motor neuron, Muscle, Pronephros, Sodium benzoate, Toxicity, Zebrafish
MeSH Terms
  • Abnormalities, Drug-Induced/pathology*
  • Abnormalities, Drug-Induced/psychology*
  • Animals
  • Antibodies, Monoclonal
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian/drug effects
  • Gastrointestinal Tract/abnormalities
  • Kidney/abnormalities
  • Kidney/growth & development
  • Larva/anatomy & histology*
  • Motor Activity/drug effects
  • Motor Neurons/drug effects
  • Motor Neurons/pathology
  • Muscle Fibers, Skeletal/drug effects
  • Muscle Fibers, Skeletal/pathology
  • Neuromuscular Junction/abnormalities
  • Neuromuscular Junction/pathology
  • Phenotype
  • Physical Stimulation
  • Receptors, Cholinergic/drug effects
  • Receptors, Cholinergic/genetics
  • Sodium Benzoate/toxicity*
  • Teratogens*
  • Time Factors
  • Zebrafish/physiology*
17644306 Full text @ Neurotoxicol. Teratol.
Sodium benzoate (SB) is a commonly used food preservative and anti-microbial agent in many foods from soup to cereals. However, little is known about the SB-induced toxicity and teratogenicity during early embryonic development. Here, we used zebrafish as a model to test the toxicity and teratogenicity because of their transparent eggs; therefore, the organogenesis of zebrafish embryos is easy to observe. After low dosages of SB (1-1000 ppm) treatment, the zebrafish embryos exhibited a 100% survival rate. As the exposure dosages increased, the survival rates decreased. No embryos survived after treatment with 2000 ppm SB. The 50% lethal dose (LD(50)) of zebrafish is found to be in the range of 1400-1500 ppm. Gut abnormalities, malformation of pronephros, defective hatching gland and edema in pericardial sac were observed after treatment with SB. Compared to untreated littermates (vehicle-treated control), SB-treated embryos exhibited significantly reduced tactile sensitivity frequencies of touch-induced movement (vehicle-treated control: 27.60+/-1.98 v.s. 1000 ppm SB: 7.89+/-5.28; N=30). Subtle changes are easily observed by staining with specific monoclonal antibodies F59, Znp1 and alpha6F to detect morphology changes in muscle fibers, motor axons and pronephros, respectively. Our data showed that the treatment of SB led to misalignment of muscle fibers, motor neuron innervations, excess acetyl-choline receptor cluster and defective pronephric tubes. On the basis of these observations, we suggest that sodium benzoate is able to induce neurotoxicity and nephrotoxicity of zebrafish larvae.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes