The influence of 0.01% sodium dodecyl sulphate, 1.5 and 6.0 M urea and 0.03 M hydrogen peroxide to the NAD(P)H: 2,6 dichlorphenolindophenol reductase activity in livers of adult and old Wistar rats during immobilizing stress was interested. Obtained results indicate that the NADPH--dependent reductase is more resistant to modulating effect of sodium dodecyl sulphate, hydrogen peroxide and urea than NADH-dependent enzyme. The significant decrease of NADH: 2.6 dichlorphenolindophenol reductase sensitivity to the action of all studied modulators occurs in old rats. The similar changes appears in the adult rats liver during stress. The old rats immobilization is accompanied by a decrease of this enzyme activity and the reduction of the influence of all studied modulators to NADH: 2.6 dichlorphenolindophenol reductase as compared with adult ones. These changes in the activity and properties of microsomal NADH: 2,6 dichlorphenolindophenol reductase promote more pronounced decrease of the substrate hydroxylation in the liver of old rats during stress compared to adult ones.
OBJECTIVES: The effect of aging on drug metabolism in humans has not yet been completely described. METHODS: Two hundred twenty-six patients with equal histopathologic conditions were investigated. The cytochrome P450 contents in the liver biopsy samples, the plasma antipyrine clearance rates after oral administration and, as an independent control of vitality, serum testosterone levels were determined. RESULTS: Cytochrome P450 content in subjects from 20 to 29 years of age was 7.2 +/- 2.6 nmol.gm-1, increased during the fourth decade (+7.2%, p = NS), declined after 40 years (-16%, p
The effect of age and gender on the in vitro biotransformation of 2-methylpropene, an alkene metabolized to 2-methyl-1,2-epoxypropane, was studied. The epoxide concentration and the epoxide metabolizing enzymatic activities were investigated in male and female Brown Norway rats of different ages. Liver tissue of senescent rats was exposed to smaller 2-methyl-1,2-epoxypropane concentrations than that of young animals, although changes during ageing were rather modest. With advancing age a feminization of male glutathione S-transferase and cytosolic epoxide hydrolase activities was found, as well as a significant decline of the female microsomal epoxide hydrolase activity and an increase of the cytochrome P-450 content in the oldest female rats.
We have previously demonstrated that age-related declines in Concanavalin A (ConA), induced proliferation and lymphokine production, occur in ad-libitum fed Brown Norway (AL BN) rats. Since caloric restriction (CR) extends lifespan, we expected that the age related changes in immune parameters would be delayed by CR. CR does act to delay age-related changes in proliferation in response to ConA. In addition, CR postpones the plateau in ConA induced interferon (IFN) production seen after 23 months of age in AL rats. However, CR does not postpone the age-related decline in ConA induced interleukin-2 (IL-2) production. Therefore, ConA induced IFN production maybe a good candidate as an early marker of physiologic aging, while ConA induced proliferative response is a possible candidate for a marker of late stages of aging.
We identified age-dependent post-translational modifications of skeletal muscle glycogen phosphorylase b (Ph-b), isolated from F1 hybrids of Fisher 344 x Brown Norway rats. Ph-b isolated from 34 months old rats showed a statistically significant decrease in specific activity compared to 6 months old animals: 13.8+/-0.7 vs. 20.6+/-0.8 U mg(-1) protein, respectively. Western blot analysis of the purified Ph-b with anti-3-NT antibodies revealed an age-dependent accumulation of 3-nitrotyrosine (3-NT), quantified by reverse-phase HPLC-UV analysis to increase from 0.05+/-0.03 to 0.34+/-0.11 (mol 3-NT/mol Ph-b) for 6 vs. 34 months old rats, respectively. HPLC-nanoelectrospray ionization-tandem mass spectrometry revealed the accumulation of 3-NT on Tyr113, Tyr161 and Tyr573. While nitration of Tyr113 was detected for both young and old rats, 3-NT at positions 161 and 573 was identified only for Ph-b isolated from 34 months old rats. The sequence of the rat muscle Ph-b was corrected based on our protein sequence mapping and a custom rat PHS2 sequence containing 17 differently located amino acid residues was used instead of the database sequence. The in vitro reaction of peroxynitrite with Ph-b resulted in the nitration of multiple Tyr residues at positions 51, 52, 113, 155, 185, 203, 262, 280, 404, 473, 731, and 732. Thus, the in vitro nitration conditions only mimic the nitration of a single Tyr residue observed in vivo suggesting alternative pathways controlling the accumulation of 3-NT in vivo. Our data show a correlation of age-dependent 3-NT accumulation with Ph-b inactivation.
The effect of age on signaling lipids contents in rat liver and different brain regions (hippocampus, neocortex) were studied. The contents of free fatty acids in the brain, diacylglycerol in liver and ceramide in all tissues studied have been found to increase with age. Age-dependent accumulation of neutral and sphingolipids evokes the violation of cell sensitivity to extracellular signals.
Laboratory of Biochemistry and Endocrinology of Aging, Institute of Children and Adolescent Health Protection, Academy of Medical Science, 50-Let VLKSM av., 52A, 61153, Kharkov, Ukraine. email@example.com
In order to investigate the possible reasons for age-related decrease in myocardium resistance to stress, we carried out a study of lipid peroxidation (LPO) stimulation features in the myocardium of adult (10-12 months) and aged (22-25 months) male Wistar rats during immobilization stress. In our studies of ascorbate-dependent LPO and induced chemiluminescence, we found that immobilization stress is accompanied by decreased efficiency in the induction of free radical processes in the heart of aged rats. An important cause of this phenomenon may be age-dependent changes in the catalytical properties of the cytosolic superoxide dismutase. The pathophysiological consequences of stress-related, age-dependent decreased efficiency of induction of free radical processes in the heart are discussed.
On the base of macro- and microelements' concentration in hair of Magadan's inhabitants there were analyzed the changes of aged people's element status. It has been shown that with age, differently directed reconstruction happened, leading to accumulation of one elements and decrease of concentration of others in inhabitants' hair. Elements, undergoing natural age reconstruction, may be considered as indicators and initiators of aging. We have allocated two groups of elements, in dependence on changes' direction. The first group is the main one; Na, K, Ca, Se, As, Mg, Mn, Fe, Zn belong to this group; their level in hair is increasing with age. Taking into account the excretory function of hair, accumulation of named elements is considered as aged removing of these elements out of organism. The exception is the toxic As: its superfluous concentrations in hair reflect the accumulation As in the internal environment of organism. Elements (Cr, Si), concentration of which in hair is decreasing with age, belong to the second group. On the base of literary data, the decreasing of named elements in hair must be interpreted as their programmed decreasing in the organism of aged people. Hence, in aged people there is seen the generalized decreasing of the most studied essential macro- and microelements in the organism. The exception is As, concentration of which is increasing in aged people. The age disorder of element homeostasis may serve as a predictor of "normal" diseases and may be one of pathophysiological mechanisms of aging.
This study aimed to investigate whether milrinone effect on cardiac muscle contractility undergoes to age-related changes. Experiments were carried out on papillary muscles isolated from right ventricle of Brown Norway rats belonging to two different age groups: 2 month old and 18 month old. The effect of milrinone (10-100 microM) on rat cardiac muscle in vitro preparations was characterized by a reduction of peak developed tension and of contraction duration. Furthermore, the recovery of contractility after a contractile cycle, i.e. the mechanical restitution was faster in the presence of milrinone than in control conditions. All these effects were reduced in preparations from 18 month old rats compared to preparations from 2 month old rats. The decrease of milrinone effect on the mechanical restitution was particularly pronounced. The reduction of the milrinone effects is likely connected with the reduction of the maximal effect of adrenergic stimulation, although the molecular basis of this link is not yet clearly understood.
The aim of this work was a comparative study of the effects of spring diseases cytogenetic years of tick-borne encephalitis in elderly and young age due to differences in genes of glutathione-S-transferase. Surveyed by routine cytogenetics 120 patients with tick-borne encephalitis residents North of Tomsk region. We have taken in the study persons aged 20-35 years (Group 1) and 65-85 years old (Group 2). Material for study (buccal epithelium) was taken from each subject 3-5 times: 1st-2nd day after hospitalization, in 1 week, 1, 3 and 6 months. Tick-borne encephalitis infection causes a significantly large changes in cytogenetic regimens using buccal epithelium in the elderly than in younger patients. Restoring cytogenetic norms observed in a group of young in 3 months after hospitalization, in the elderly - in 6 months. When comparing cytogenetic effects of encephalitis shows: the young patients tick-borne encephalitis level by routine cytogenetics abnormal cells was significantly higher in carriers of inactive forms of gene GSTM1 (0)/GSTT1 (0) than containing active homozygous variants of these genes. Such patterns have not been noted in a group of elderly patients.