Hexavalent Chromium Induces Neurotoxicity by Triggering Mitochondrial Dysfunction and ROS-Mediated Signals.

Area of Science:

• Environmental toxicology
• Neuroscience
• Cellular toxicology

Background:

• Hexavalent chromium (Cr (VI)) is a widespread environmental pollutant with known systemic toxicity.
• Cr (VI)-induced neurotoxicity, particularly at the primary neuron level, remains underexplored.
• Understanding Cr (VI) effects on neurons is crucial for public health and environmental safety.

Purpose of the Study:

• To investigate the neurotoxic effects of Cr (VI) on primary rat hippocampal neurons.
• To elucidate the underlying mechanisms of Cr (VI)-induced neurotoxicity, focusing on mitochondrial function and oxidative stress.
• To assess the potential protective role of glutathione (GSH) against Cr (VI) neurotoxicity.

Main Methods:

• Primary rat hippocampal neurons were exposed to potassium dichromate (K2Cr2O7) to model Cr (VI) exposure.
• Neural viability was assessed using the MTT assay.
• Mitochondrial dysfunction was evaluated using JC-1 and Mito-Tracker probes.
• Oxidative stress markers, including reactive oxygen species (ROS) and DNA damage, were measured using DCFH-DA and Mito-SOX Red.
• Expression levels of Bcl-2 family proteins and MAPKs were analyzed via Western blotting.

Main Results:

• Cr (VI) exposure significantly inhibited neural viability in a dose- and time-dependent manner.
• Cr (VI) induced mitochondrial dysfunction by altering Bcl-2 family protein expression.
• Increased intracellular ROS generation, DNA damage, and MAPKs activation were observed following Cr (VI) treatment.
• Glutathione (GSH) administration effectively counteracted Cr (VI)-induced ROS production, restored Bcl-2 family expression, attenuated DNA damage, and reduced MAPKs activation, ultimately improving neural viability.

Conclusions:

• Cr (VI) exerts significant neurotoxicity in primary hippocampal neurons.
• The neurotoxic mechanisms involve Cr (VI)-induced mitochondrial dysfunction, ROS-mediated oxidative damage, and MAPKs pathway activation.
• Glutathione (GSH) demonstrates a protective effect against Cr (VI) neurotoxicity by mitigating oxidative stress and associated cellular damage.