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Age-related changes in hepatic activity and expression of detoxification enzymes in male rats

Erika Vyskočilová1, Barbora Szotáková, Lenka Skálová

  • 1Department of Biochemical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic.

Biomed Research International
|August 24, 2013
PubMed

Insights

Aging alters drug metabolism and antioxidant enzyme activity in rats. While some enzymes decrease, glutathione S-transferase (GST) and carbonyl reductase 1 (CBR1) significantly increase in older rats, potentially offering protection but affecting drug processing.

Area of Science:

  • Pharmacology
  • Biochemistry
  • Gerontology

Background:

  • Aging is associated with altered xenobiotic metabolism and cellular damage from free radicals.
  • Understanding age-related changes in drug-metabolizing and antioxidant enzymes is crucial for predicting drug efficacy and toxicity in elderly populations.

Purpose of the Study:

  • To investigate age-dependent variations in the activity and expression of key drug-metabolizing and antioxidant enzymes in rats.
  • To compare enzyme profiles in young versus senescent Wistar rats.

Main Methods:

  • Assessed specific activities of 8 drug-metabolizing and 4 antioxidant enzymes in hepatic subcellular fractions from young (6-week-old) and old (21-month-old) male Wistar rats.
  • Determined protein expression of carbonyl reductase 1 (CBR1) and glutathione S-transferase (GST) using immunoblotting.

Main Results:

  • Significant age-related decreases were observed in the activities of CYP2B, CYP3A, and UDP-glucuronosyl transferase.
  • Activities of CYP1A2, flavine monooxygenase, aldo-keto reductase 1C, and antioxidant enzymes remained unchanged with age.
  • Specific activities of CBR1 and GST were markedly higher (2.4-fold and 5.6-fold, respectively) in senescent rats compared to young rats.
  • Interindividual variability in CBR1 activity increased with age.

Conclusions:

  • Elevated GST and CBR1 activities in senescent rats may confer protection against electrophilic and reactive carbonyl species.
  • These age-associated enzymatic changes could potentially alter the metabolism of drugs that are substrates for CBR1 and GSTs.

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