Age-Related Changes in Hepatic Activity and Expression of Detoxification Enzymes in Male Rats

Abstract

Process of aging is accompanied by changes in the biotransformation of xenobiotics and impairment of normal cellular functions by free radicals. Therefore, this study was designed to determine age-related differences in the activities and/or expressions of selected drug-metabolizing and antioxidant enzymes in young and old rats. Specific activities of 8 drug-metabolizing enzymes and 4 antioxidant enzymes were assessed in hepatic subcellular fractions of 6-week-old and 21-month-old male Wistar rats. Protein expressions of carbonyl reductase 1 (CBR1) and glutathione S-transferase (GST) were determined using immunoblotting. Remarkable age-related decrease in specific activities of CYP2B, CYP3A, and UDP-glucuronosyl transferase was observed, whereas no changes in activities of CYP1A2, flavine monooxygenase, aldo-keto reductase 1C, and antioxidant enzymes with advancing age were found. On the other hand, specific activity of CBR1 and GST was 2.4 folds and 5.6 folds higher in the senescent rats compared with the young ones, respectively. Interindividual variability in CBR1 activity increased significantly with rising age. We suppose that elevated activities of GST and CBR1 may protect senescent rats against xenobiotic as well as eobiotic electrophiles and reactive carbonyls, but they may alter metabolism of drugs, which are CBR1 and especially GSTs substrates.

Expression Profiles of Cytochrome P450s Following Swimming Exercise in Aging Rats

“…Moreover, CYP2C11 and CYP3A2 expression has been shown to decrease with age. 39,40 Similarly, our study confirmed that long-term regular exercise could delay the age-related decreases in some CYPs and DMEs.…”

Oxidative stress response and Nrf2 signaling in aging

“…Animal studies also showed an age-dependent decrease in SOD1 activity in liver [70, 71], and brain [72, 73] of old rats. In contrast, no age-related differences in SOD1 activity were reported in erythrocytes [74], plasma [75], lymphocytes [76], plasma [77], and muscles [78] from human subjects of different ages, or in rat liver (21 mo vs. 6 w) [79]. In addition, some studies even showed that SOD1 activity was increased with aging in some tissues, such as mouse skeletal muscles, rat brain [80], and human plasma [81].…”

Determination of acrylamide-induced chick embryo brain glutathione S-transferases expression through enzyme activity and western blot

“…Usually, ROS can damage macromolecules under oxidative stress conditions, while antioxidant enzymes of the body are expressed more [38]. It was reported that the increased activities of GST may protect rat from xenobiotic, and they alter drug metabolism that is, especially, GST substrates [39]. ACR is potent neurotoxin [15,40] and can induce neurotoxicity in both prenatal and perinatal rodents [41,42].…”