Treatment with sodium benzoate leads to malformation of zebrafish larvae.
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.
Tsay
Huey-Jen
HJ
Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.
Wang
Yun-Hsin
YH
Chen
Wei-Li
WL
Huang
Mei-Yun
MY
Chen
Yau-Hung
YH
D000014:Abnormalities, Drug-Induced / Q000473:pathology* / Q000523:psychology*; D000818:Animals; D000911:Antibodies, Monoclonal; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000002:abnormalities; D007668:Kidney / Q000002:abnormalities / Q000254:growth & development; D007814:Larva / Q000033:anatomy & histology*; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D009469:Neuromuscular Junction / Q000002:abnormalities / Q000473:pathology; D010641:Phenotype; D010812:Physical Stimulation; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000235:genetics; D020160:Sodium Benzoate / Q000633:toxicity*; D013723:Teratogens; D013997:Time Factors; D015027:Zebrafish / Q000502:physiology*
D000911:Antibodies, Monoclonal; D011950:Receptors, Cholinergic; D013723:Teratogens; D020160:Sodium Benzoate