Suppression of acrylamide toxicity by carboxyfullerene in human neuroblastoma cells in vitro
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Updated: Jun 22, 2026
A Neuronal and Astrocyte Co-Culture Assay for High Content Analysis of Neurotoxicity
Published on: May 5, 2009
Tomoyuki Sumizawa1, Hideki Igisu
1Department of Environmental Toxicology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Iseigaoka, Yahatanishi, Kitakyushu, Japan.
Abstract:
In our previous study, we found that caspase-dependent apoptosis played a role in the genesis of toxicity of acrylamide in human neuroblastoma (SH-SY5Y) cells (Sumizawa and Igisu in Arch Toxicol 81:279-282, 2007). In the present experiment, we examined whether carboxyfullerene may suppress the cytotoxicity of acrylamide because carboxyfullerene has been reported to protect nerve cells from various pathologic processes including apoptosis. Carboxyfullerene lowered lactate dehydrogense leakage and elevated cell viability in SH-SY5Y cells exposed to acrylamide. It also lowered caspase-3 activities and cell population in the sub-G(1) phase induced by acrylamide. Nevertheless, carboxyfullerene enhanced cellular uptake of [(14)C]acrylamide. On the other hand, acrylamide markedly decreased glutathione (GSH)-content in cells and carboxyfullerene blocked the decrease. The toxicity of acrylamide was suppressed by adding GSH or GSH monoethyl ester, whereas it was not lowered by carboxyfullerene when GSH synthesis was inhibited by L: -buthionine-(S,R)-sulfoximine. Thus, the cytotoxicity of acrylamide including apoptotic processes is closely related to GSH level in SH-SY5Y cells and carboxyfullerene suppresses the toxicity by maintaining GSH content. Neither tricarboxylic acids without fullerene moiety nor hydroxylated fullerene showed comparable effects of carboxyfullerene (60 microM) against 1-5 mM acrylamide, suggesting the importance of the three malonic acid groups at specific positions in a fullerene molecule for the effects.
Insights
Carboxyfullerene protects human neuroblastoma cells from acrylamide toxicity by maintaining glutathione levels. This neuroprotective effect involves suppressing apoptosis and is linked to the fullerene's specific chemical structure.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Acrylamide is a neurotoxicant implicated in apoptosis in human neuroblastoma (SH-SY5Y) cells.
- Carboxyfullerene is known to protect nerve cells from various pathological processes, including apoptosis.
Purpose of the Study:
- To investigate the potential of carboxyfullerene in suppressing acrylamide-induced cytotoxicity in SH-SY5Y cells.
- To elucidate the mechanism underlying carboxyfullerene's neuroprotective effects against acrylamide.
Main Methods:
- Assessing lactate dehydrogenase leakage and cell viability in SH-SY5Y cells exposed to acrylamide.
- Measuring caspase-3 activity and cell cycle distribution (sub-G1 phase).
- Quantifying cellular glutathione (GSH) levels and evaluating the impact of GSH modulation.
Main Results:
- Carboxyfullerene reduced acrylamide-induced cell death and apoptosis markers (caspase-3 activity, sub-G1 population).
- Carboxyfullerene prevented the depletion of intracellular glutathione (GSH) caused by acrylamide.
- The protective effect of carboxyfullerene was dependent on GSH levels, as it was diminished when GSH synthesis was inhibited.
Conclusions:
- Acrylamide's cytotoxicity in SH-SY5Y cells is closely linked to its impact on cellular GSH levels.
- Carboxyfullerene exerts neuroprotection against acrylamide by preserving GSH content.
- The specific structure of carboxyfullerene, particularly the malonic acid groups, is crucial for its protective effects.
