Time-dependent effects of o-xylene on rat lung and liver microsomal membrane structure and function

Area of Science:

• Toxicology
• Biochemistry
• Pharmacology

Background:

• Mixed-function oxidase (MFO) systems are crucial for xenobiotic metabolism.
• Previous studies indicated isomer-specific effects of xylene on MFOs.
• Understanding o-xylene's impact on MFOs and membrane integrity is vital for risk assessment.

Purpose of the Study:

• To investigate the time-dependent effects of o-xylene on rat hepatic and pulmonary MFO content and activity.
• To assess the impact of o-xylene on microsomal membrane structural parameters.
• To compare o-xylene's effects with those of its isomers (m- and p-xylene).

Main Methods:

• Acute intraperitoneal administration of o-xylene (1 g/kg) to rats.
• Measurement of cytochrome P-450 content and MFO activities (AHH, EROD, BROD) at various time points up to 12 h.
• Analysis of microsomal membrane parameters: conjugated diene formation, phospholipid, and cholesterol content.

Main Results:

• o-Xylene decreased pulmonary cytochrome P-450, AHH, EROD, and BROD activities.
• Hepatic cytochrome P-450 content increased, with elevated EROD and markedly increased BROD activities.
• Pulmonary and hepatic membrane lipid peroxidation (CD formation) and lipid content (PL, CL) were altered, suggesting organ-selective toxicological effects.

Conclusions:

• o-Xylene induces organ-selective alterations in MFO activity and microsomal membrane integrity in rats.
• The observed lipid changes are likely independent toxicological effects rather than causal factors for MFO alterations.
• Metabolism of other xenobiotics may be affected in an organ-specific manner following o-xylene exposure.