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Age and sex related differences in some rat renal NADPH-consuming detoxification enzymes
Abstract:
Age- and sex-associated changes in some renal drug-metabolizing enzyme activities (NADPH-cytochrome c reductase, the glutathione peroxidase-glutathione reductase system, and thioredoxin reductase) were investigated using male and female Wistar rats (ages ranging from -4 days to 24 months). During aging the activities of NADPH-cytochrome c reductase and thioredoxin reductase showed a marked decrease (approximately 50% in both enzymes compared to adult stage). Glutathione reductase activity presented similar values in adulthood and aging, and glutathione peroxidase activity showed an increase with age (30% compared with the adult values). A marked sex difference was observed in young rats for glutathione peroxidase and thioredoxin reductase activities. However, during aging this difference disappears for glutathione peroxidase activity, but it remains for thioredoxin reductase activity (the specific activity in male old rats was approximately two-fold that obtained from female old rats). The variations in these enzymatic activities may be important when determining the changes in susceptibility of the kidneys to toxic chemicals with aging.
Insights
Kidney drug-metabolizing enzyme activities change with age and sex. NADPH-cytochrome c reductase and thioredoxin reductase decrease, while glutathione peroxidase increases, impacting toxic chemical susceptibility.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Renal drug metabolism is crucial for xenobiotic clearance.
- Aging and sex are known modulators of enzyme activity.
- Understanding these changes is vital for predicting drug efficacy and toxicity.
Purpose of the Study:
- To investigate age- and sex-associated changes in key renal drug-metabolizing enzymes.
- To determine how these enzymatic alterations affect kidney susceptibility to toxic chemicals.
Main Methods:
- Wistar rats of both sexes and varying ages (prenatal to 24 months) were used.
- Activities of NADPH-cytochrome c reductase, glutathione peroxidase, glutathione reductase, and thioredoxin reductase were measured.
- Enzyme activities were compared across different age groups and between sexes.
Main Results:
- NADPH-cytochrome c reductase and thioredoxin reductase activities significantly decreased with age (~50%).
- Glutathione peroxidase activity increased with age (~30%), while glutathione reductase remained stable.
- Sex differences in glutathione peroxidase diminished with age, but persisted for thioredoxin reductase (males > females in old rats).
Conclusions:
- Aging significantly alters renal drug-metabolizing enzyme profiles.
- Sex-specific differences in enzyme activity are age-dependent.
- These age- and sex-related enzymatic variations can influence kidney susceptibility to toxic agents.