Senescent changes in rodent hepatic epoxide metabolism

Area of Science:

• Biochemistry
• Toxicology
• Gerontology

Background:

• Epoxide metabolism is crucial for detoxification.
• Age-related changes in metabolic enzymes can affect toxicity and drug response.
• Rodent models are used to study aging processes.

Purpose of the Study:

• To investigate age-related changes in hepatic epoxide metabolism in rats and mice.
• To determine the impact of polychlorinated biphenyls (PCBs) on epoxide-metabolizing enzymes in aged rodents.

Main Methods:

• Assessed glutathione-S-transferase and epoxide hydrase activities in liver subcellular fractions from rats and mice of different ages (3, 12, and >24 months).
• Measured microsomally-mediated binding of benzo[a]pyrene to DNA.
• Examined the effects of PCB pretreatment on enzyme activities.

Main Results:

• Epoxide hydrase activity increased with age in both species, while glutathione-S-transferase remained unchanged.
• Increased binding of benzo[a]pyrene to DNA was observed in older animals.
• PCBs induced glutathione-S-transferase only in old animals; epoxide hydrase induction by PCBs showed species- and age-specific differences.

Conclusions:

• Aging rodents generally retain or enhance their capacity for epoxide metabolism.
• There are significant age- and species-dependent differences in the response of epoxide-metabolizing enzymes to PCB exposure.