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Cortical astrocytes exposed to tributyltin undergo morphological changes in vitro
S Mizuhashi1, Y Ikegaya, N Nishiyama
1Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
Japanese Journal of Pharmacology
|January 4, 2001
Summary
Tributyltin (TBT), an endocrine disruptor, causes rat astrocyte cells to change shape and die via oxidative stress. Antioxidants and signaling pathway inhibitors protected cells, indicating TBT
Area of Science:
- Neuroscience
- Environmental Toxicology
- Cell Biology
Background:
- Endocrine-disrupting chemicals (EDCs) pose risks to mammalian health.
- Tributyltin (TBT) is a widely used EDC with known toxic effects.
- Astrocytes play crucial roles in central nervous system function and protection.
Purpose of the Study:
- To investigate the effects of TBT on the morphology and viability of cultured rat cortical astrocytes.
- To elucidate the mechanisms underlying TBT-induced astrocyte morphological changes.
- To determine if TBT's effects are mediated by oxidative stress or specific signaling pathways.
Main Methods:
- Primary rat cortical astrocyte cultures were exposed to varying concentrations of TBT.
- Morphological changes were assessed using microscopy.
- Cell viability was measured using standard assays.
- Pharmacological agents, including free radical scavengers, antioxidants, and signaling pathway inhibitors, were used to probe mechanisms.
Main Results:
- TBT exposure induced time- and concentration-dependent morphological changes in astrocytes, characterized by cell body "stellation" (asteriated appearance with process formation).
- Higher TBT concentrations led to progressive astrocyte cell death.
- TBT-induced stellation was significantly reduced by free radical scavengers and antioxidants, implicating oxidative stress (reactive oxygen species).
- Inhibition of phospholipase C, mitogen-activated protein kinase kinase, or tyrosine phosphatase abolished TBT-induced stellation, suggesting involvement of specific intracellular signaling cascades.
Conclusions:
- TBT induces astrocyte stellation and cell death through oxidative stress and specific intracellular signaling pathways, not solely non-specific toxicity.
- These findings offer insights into the neurotoxic mechanisms of the environmental pollutant TBT.
- Understanding these pathways is crucial for assessing the risks of TBT exposure to mammals.