In vivo effects of chromium

Area of Science:

• Toxicology
• Cell Biology
• Biochemistry

Background:

• Hexavalent chromium (Cr(VI)) is a known toxicant.
• Understanding Cr(VI) cellular mechanisms is crucial for risk assessment.
• Previous studies indicate Cr(VI) can induce oxidative stress.

Purpose of the Study:

• To investigate the production of reactive oxygen species (ROS) in lung cells exposed to Cr(VI).
• To characterize the effects of Cr(VI) on specific cytochrome P450 isozymes in rat liver and lung microsomes.
• To explore potential sex-specific differences in Cr(VI) toxicity.

Main Methods:

• A549 lung cells were treated with potassium dichromate (K2Cr2O7) and ROS production was measured using flow cytometry with 2",7"-dichlorofluorescein diacetate.
• Electron paramagnetic resonance (EPR) spectroscopy was employed to detect free radicals and Cr(V) species.
• Liver and lung microsomes from male and female Sprague-Dawley rats, treated with K2Cr2O7, were analyzed for cytochrome P450 activity.

Main Results:

• Cr(VI) exposure led to a dose-dependent increase in ROS production in A549 cells.
• Trivalent chromium (Cr(III)) compounds did not induce ROS.
• EPR studies identified free radical and Cr(V) signals.
• Cr(VI) treatment decreased cytochrome P450 3A1/3A2 and 2C11 activity in male rat liver microsomes.
• In contrast, female rat liver microsomes showed increased activity of these isozymes.
• Male rat lung microsomes exhibited increased P450 2C11 activity.

Conclusions:

• Cr(VI) induces oxidative stress in lung cells.
• Cr(VI) exposure significantly impacts the activity of key drug-metabolizing enzymes, with notable sex-specific effects.
• These findings highlight the complex toxicological profile of Cr(VI) and its differential effects based on sex and tissue type.