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Updated: Dec 4, 2025
Nephrotoxin Microinjection in Zebrafish to Model Acute Kidney Injury
Published on: July 17, 2016
A new aminoglycoside etimicin shows low nephrotoxicity and ototoxicity in zebrafish embryos
Weihao Shao1, Dan Zhong1, Haowei Jiang1
1Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Abstract:
Aminoglycoside antibiotics are widely used for many life-threatening infections. The use of aminoglycosides is often comprised by their deleterious side effects to the kidney and inner ear. A novel semisynthetic antibiotic, etimicin, has good antimicrobial activity against both gram-positive and gram-negative bacteria. But its toxicity profile analysis is still lacking. In the present study, we compared the in vivo toxic effects of three aminoglycosides, gentamicin, amikacin, and etimicin, in zebrafish embryos. We examined the embryotoxicity, nephrotoxicity, and the damage to the neuromast hair cells. Our results revealed that etimicin and amikacin exhibit more developmental toxicities to the young embryos than gentamicin. But at subtoxic doses, etimicin and amikacin show significantly reduced toxicities towards kidney and neuromast hair cells. We further demonstrated that fluorescently conjugated aminoglycosides (gentamicin-Texas red [GTTR], amikacin-Texas red [AMTR], and etimicin-Texas red [ETTR]) all enter the hair cells properly. Inside the hair cells, gentamicin, not etimicin and amikacin, displays robust reactive oxygen species generation and induces apoptosis. Our data support that the different intracellular cytotoxicity underlies the different ototoxicity of the three aminoglycosides and that etimicin is a new aminoglycoside with reduced risk of nephrotoxicity and ototoxicity.
Insights
Etimicin, a novel aminoglycoside antibiotic, shows reduced kidney and inner ear toxicity compared to gentamicin and amikacin in zebrafish embryos. This suggests etimicin may be a safer alternative for treating infections.
Area of Science:
- Pharmacology
- Toxicology
- Developmental Biology
Background:
- Aminoglycoside antibiotics are crucial for treating severe infections but can cause kidney and inner ear damage.
- Etimicin is a new semisynthetic aminoglycoside with broad-spectrum activity, but its toxicity is not well-characterized.
- Understanding the comparative toxicity of aminoglycosides is essential for developing safer therapeutic options.
Purpose of the Study:
- To compare the in vivo toxic effects of etimicin, gentamicin, and amikacin in zebrafish embryos.
- To evaluate the embryotoxicity, nephrotoxicity, and ototoxicity of these aminoglycosides.
- To elucidate the mechanisms underlying differential aminoglycoside-induced ototoxicity.
Main Methods:
- Zebrafish embryos were exposed to gentamicin, amikacin, and etimicin.
- Embryonic development, kidney function, and neuromast hair cell damage were assessed.
- Fluorescently conjugated aminoglycosides were used to track cellular uptake and intracellular effects, including reactive oxygen species (ROS) generation and apoptosis.
Main Results:
- Etimicin and amikacin displayed higher developmental toxicity in early zebrafish embryos than gentamicin.
- At subtoxic doses, etimicin and amikacin showed significantly lower toxicity to kidneys and neuromast hair cells.
- Gentamicin induced higher ROS generation and apoptosis within hair cells compared to etimicin and amikacin.
Conclusions:
- Differential intracellular cytotoxicity, particularly ROS generation and apoptosis, explains the varying ototoxicity of these aminoglycosides.
- Etimicin demonstrates a reduced risk of nephrotoxicity and ototoxicity, positioning it as a promising alternative aminoglycoside antibiotic.
