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Analysis of Oxidative Stress in Zebrafish Embryos
Published on: July 7, 2014
Zebrafish Model-Based Assessment of Indoxyl Sulfate-Induced Oxidative Stress and Its Impact on Renal and Cardiac
Paul Wei-Hua Tang1,2, Ping-Hsun Wu3, Yi-Ting Lin4
1Department of Internal Medicine, Taipei Veterans General Hospital Yuli Branch, Hualien 981, Taiwan.
Abstract:
Kidney disease patients may have concurrent chronic kidney disease-associated mineral bone disorder and hypertension. Cardiovascular disease (CVD) and neuropathy occur due to kidney failure-induced accumulation of uremic toxins in the body. Indoxyl sulfate (IS), a product of indole metabolism in the liver, is produced from tryptophan by the intestinal flora and is ultimately excreted through the kidneys. Hemodialysis helps renal failure patients eliminate many nephrotoxins, except for IS, which leads to a poor prognosis. Although the impacts of IS on cardiac and renal development have been well documented using mouse and rat models, other model organisms, such as zebrafish, have rarely been studied. The zebrafish genome shares at least 70% similarity with the human genome; therefore, zebrafish are ideal model organisms for studying vertebrate development, including renal development. In this study, we aimed to investigate the impact of IS on the development of zebrafish embryos, especially cardiac and renal development. At 24 h postfertilization (hpf), zebrafish were exposed to IS at concentrations ranging from 2.5 to 10 mM. IS reduced survival and the hatching rate, caused cardiac edema, increased mortality, and shortened the body length of zebrafish embryos. In addition, IS decreased heart rates and renal function. IS affected zebrafish development via the ROS and MAPK pathways, which subsequently led to inflammation in the embryos. The results suggest that IS interferes with cardiac and renal development in zebrafish embryos, providing new evidence about the toxicity of IS to aquatic organisms and new insights for the assessment of human health risks. Accordingly, we suggest that zebrafish studies can ideally complement mouse model studies to allow the simultaneous and comprehensive investigation of the physiological impacts of uremic endotheliotoxins, such as IS, on cardiac and renal development.
Insights
Indoxyl sulfate (IS) harms zebrafish embryo development, impacting cardiac and renal systems. This study highlights IS toxicity and suggests zebrafish as a complementary model for assessing human health risks from uremic toxins.
Area of Science:
- Toxicology
- Developmental Biology
- Zebrafish Models
Background:
- Chronic kidney disease (CKD) patients often have co-occurring mineral bone disorder and hypertension.
- Uremic toxins, like indoxyl sulfate (IS), accumulate in kidney failure, contributing to cardiovascular disease (CVD) and neuropathy.
- IS is poorly cleared by hemodialysis, leading to poor prognosis in renal failure patients.
Purpose of the Study:
- To investigate the impact of indoxyl sulfate (IS) on zebrafish embryo development, focusing on cardiac and renal systems.
- To explore the potential of zebrafish as a model organism for studying the toxic effects of uremic toxins.
- To elucidate the molecular pathways involved in IS-induced developmental toxicity.
Main Methods:
- Zebrafish embryos were exposed to varying concentrations of IS (2.5–10 mM) starting at 24 hours postfertilization (hpf).
- Assessed developmental parameters including survival, hatching rate, body length, cardiac edema, heart rate, and renal function.
- Investigated the roles of reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) pathways in IS toxicity.
Main Results:
- IS exposure significantly reduced survival, hatching rates, and body length in zebrafish embryos.
- Cardiac edema and decreased heart rates were observed, indicating cardiotoxicity.
- Renal function was impaired, and IS-induced developmental defects were linked to ROS/MAPK pathway activation and subsequent inflammation.
Conclusions:
- Indoxyl sulfate (IS) demonstrably interferes with cardiac and renal development in zebrafish embryos.
- This study provides novel evidence of IS toxicity in aquatic organisms and informs human health risk assessments.
- Zebrafish offer a valuable complementary model to mammalian studies for investigating the physiological impacts of uremic toxins like IS.
