Old age-associated impairment of the rat liver antioxidant defense system: the basis for affirmation of the experimental model

Abstract

To the Editor, Keeping in mind our recent breakthrough in the field of biomedical effects of citrus flavanones, achieved by using an insufficiently exploited rat experimental model of old age (1,2), we consider it important to highlight the status of the antioxidative defense system in this animal model, as it is a crucial physiological definer. In general, aging represents a complex process characterized by the deterioration of overall health, slowing of the metabolism, and accumulation of numerous mutations (3). The United Nations World Population Aging Report in 2015 suggested that 12.5% of the entire human population is older than 60 years, while some demographic assessments of the World Bank predict it to reach 17% older than 65 years by 2050. Aging is associated with elevated incidences of chronic diseases, such as diabetes, hypertension, dyslipidemia, liver function disturbances, endocrine issues, osteoporosis, sarcopenia, and cancer (3,4). Changes in the antioxidant defense system (ADS), detoxification mechanisms, and cell reparation underlie the majority of the mentioned diseases (5). Namely, as a consequence of the decrease in ADS and cell reparation capacities during aging, the rate of oxidative damage increases. If reactive oxygen species (ROS) are not efficiently removed from the milieu, accumulation of oxidized and glycoxidized products can subsequently cause cellular senescence (6). It is well known that antioxidant enzymes such as superoxide dismutase (SOD) 1 and 2, catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), as well as nonenzymatic glutathione (GSH), eliminate ROS such as superoxide anion (O 2− ) or hydrogen peroxide (H 2 O 2 ). As a consequence of the lack of their efficient removal, this can lead to damage of cellular proteins, lipids, and organelles. Oxidative metabolism in the liver causes the production of highly reactive ROS, whereby 90% of these molecules are generated in the mitochondria during the process of aerobic

Citrus Flavanones Upregulate Thyrotroph Sirt1 and Differently Affect Thyroid Nrf2 Expressions in Old-Aged Wistar Rats

“…19,42 Thus, this is the first report showing that supplementation with nutritionally relevant doses of NAR and HES is not just safe but also favorable regarding inactivation of rat's thyroid with advanced age. 39 Furthermore, we showed that Nrf2 protein expression increased while its gene expression decreased after NAR. Higher Nrf2 protein accumulation in the thyroid is in line with studies showing upregulation of its expression by polyphenols.…”

“…Discrepancy in obtained results is most likely because of the difference in administrated doses because doses used by other research groups were 50 mg/kg and 1.5 g/kg of b.m. According to the hormesis concept, moderate and chronic consumption of low doses of polyphenols can induce mild stress response, which can by preconditioning provide a healthy and improved physiological environment in the cell. , Thus, this is the first report showing that supplementation with nutritionally relevant doses of NAR and HES is not just safe but also favorable regarding inactivation of rat’s thyroid with advanced age …”

“…To represent rapidly growing human population of elderly, we used the animal model of naturally aged rats. The model was characterized by lower serum TH levels, along with unchanged serum TSH levels. − In our previous study, 15 mg/kg b.m. of NAR or HES improved thyroid gland capacity to produce and accumulate THs, showing the structurally active gland …”

Age related changes in the expression of tenascin-c in liver of albino rat

“…8 In agreement of the current study Ying et al 9 used rats 6, 12, 18 and 24 months old and found that there was marked increase in body weight and liver weight in 6, 12 and 18 age group rats followed by a decrease in body weight and liver weight in 24 age group rats. 9 Miler et al 10 used rats 4 d 24 months old, and they mentioned that the functional status of the liver was achieved by measuring the concentration of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl trans-peptidase (GGT) in the serum of young and old rats. The results obtained displayed an old age-associated 4-folds increase in GGT concentration when compared to young rats.…”

“…These findings support the result of the current study. 10 Serum lipid levels are related to age total cholesterol (TC) gradually increase after adolescence. Triglycerides changeless during adulthood but tends to be higher in old age.…”