scholarly journals Decoding Aging: Understanding the Complex Relationship among Aging, Free Radicals, and GSH

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
María E. López-Navarro ◽  
Mariana Jarquín-Martínez ◽  
Luis A. Sánchez-Labastida ◽  
Daniel Ramírez-Rosales ◽  
Marycarmen Godínez-Victoria ◽  
...  
Keyword(s):  
Free Radicals ◽  
Ex Vivo ◽  
Redox Homeostasis ◽  
Adult Rats ◽  
Paramagnetic Resonance ◽  
Young Rats ◽  
Male Wistar Rats ◽  
Michael Type Addition ◽  
Old Rats ◽  
In Cells

N-aryl maleimides can undergo a 1,4-Michael-type addition reaction with reduced glutathione (GSH), leading to a decreased concentration of GSH and an increased concentration of free radicals (FRs) in cells. GSH is a critical scavenging molecule responsible for protecting cells from oxidation and for maintaining redox homeostasis. N-aryl maleimides disturb redox homeostasis in cells because they scavenge thiol-containing molecules, especially GSH. This study aimed at measuring the concentrations of GSH and FRs by electronic paramagnetic resonance (EPR), in the brain and liver tissue of male Wistar rats (ex vivo) at different ages and after treatment with 3,5-dimaleimylbenzoic acid (3,5-DMB). Our results showed a relationship between age and the concentrations of GSH and FRs in cells. In young rats, the concentration of GSH was higher than in old rats, while the concentration of FRs was higher in adult rats than in young rats, suggesting an inverse relationship between GSH and FRs. On the other hand, the reaction of 3,5-DMB (an electrophilic maleimide) with cellular GSH increased the FR content. The results of this study contribute to the awareness that the process of aging implies not only a loss of tissue function but also essential changes in the molecular contents of cells, especially the concentrations of FRs and GSH.

Developmental study of benzodiazepine effects on monosynaptic GABAA-mediated IPSPs of rat hippocampal neurons

1993 ◽  
Vol 70 (3) ◽  
pp. 1076-1085 ◽  
Author(s):  
C. Rovira ◽  
Y. Ben-Ari
Keyword(s):  
Hippocampal Neurons ◽  
Receptor Agonist ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Developmental Study ◽  
Type I ◽  
Gamma Aminobutyric Acid ◽  
Adult Rats ◽  
Young Rats ◽  
In Cells

1. The effects of type I (BZ1) and type II (BZ2) benzodiazepine receptor ligands on monosynaptic gamma-aminobutyric acid (GABA)A-mediated inhibitory postsynaptic potentials (IPSPs) and on responses to exogenously applied GABA were studied using intracellular recordings from CA3 pyramidal cells of rat hippocampal slices taken at different postnatal stages [postnatal day 4 (P4)-P35)]. 2. The effects of midazolam, a BZ1 and BZ2 receptor agonist, were tested on the monosynaptic IPSPs at different stages. Monosynaptic, bicuculline-sensitive IPSPs were evoked by hilar stimulation in presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) antagonists [6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) and D(-)2-amino-5-phosphonopentanoic acid (50 microM)]. Midazolam at 300 nM maximally increased the duration and amplitude of monosynaptic GABAA-mediated IPSPs in neurons from pups (P4-P6, n = 6) and young (P7-P12, n = 8) and adult (P25-P35, n = 9) rats. All the effects of midazolam on IPSPs were reversed by the antagonist Ro 15-1788 (10 microM). 3. The effect of midazolam was also tested on the response to exogenously applied GABA (5 mM) in the presence of tetrodotoxine [TTX (1 microM)]. In neurons from young rats (n = 9), midazolam (1 nM-1 microM) did not change the responses to exogenously applied GABA, whereas in adult rats (n = 8) midazolam maximally increased GABA currents at 30 nM. 4. The effect of zolpidem, a BZ1 receptor agonist, was tested on monosynaptic IPSPs and GABA currents at different stages. Zolpidem (10 nM-1 microM) was inactive in cells from young rats (n = 12). In neurons from adult rats, zolpidem maximally increased the duration and amplitude of the monosynaptic IPSPs at 300 nM (n = 5) and the amplitude of GABA current at 30-100 nM (n = 5). 5. Methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) (300 nM), an inverse agonist of BZ1 and BZ2 receptors, decreased the amplitude and duration of monosynaptic IPSPs in neurons from pups (n = 3) and young (n = 4) and adult (n = 5) rats. In all cases, full recovery was obtained after exposure to R0 15-1788 (10 microM). DMCM (300 nM-10 microM) failed to reduce GABA responses in cells from young (n = 3) or adult (n = 7) rats. 6. Results indicate that the regulation by benzodiazepine of GABAA-mediated IPSPs varies with the developmental stage.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Cell-Free DNA Plasma Levels Differ in Age-Specific Pattern in Healthy Rats and Castrates with Testosterone-Induced Benign Prostatic Hyperplasia

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
I. N. Vasilyeva ◽  
V. G. Bespalov ◽  
J. D. Von ◽  
A. L. Semenov ◽  
G. V. Tochilnikov ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Wistar Rats ◽  
Specific Pattern ◽  
Prostatic Hyperplasia ◽  
The Body ◽  
Cell Free Dna ◽  
Young Rats ◽  
Free Dna ◽  
Male Wistar Rats ◽  
Old Rats

The purpose of this work was to study changes in the level of cell-free DNA (cfDNA) in the blood of young and old rats in the normal state and with induced benign prostatic hyperplasia (BPH). Male Wistar rats were divided into 4 groups—young (3 months), old (20 months), intact, or with testosterone-induced BPH. Groups with BPH were subjected to surgical castration and administration of testosterone esters at a dose of 25 mg/kg for a total of 7 injections for 20 days. In intact animals, the level of cfDNA in old rats (2.00±0.14 ng/μl) was significantly higher than that in the young (1.02±0.30 ng/μl). The body and the prostate weights of old rats were 1.6 and 1.4 times larger than those of the young, without an increase in the prostate index (PI). The testosterone level in the blood of young rats was 1.6 times higher than that of old (6.20±0.93 nmol/l vs. 3.77±0.55 nmol/l; NS). In animals with BPH, the level of cfDNA in old rats (3.14±0.76 ng/μl) was significantly higher than that in young rats (0.80±0.14 ng/μl). The body and the prostate weights in old rats were 1.8 and 2.3 times larger, than those in young rats, with an increase in the PI. The level of testosterone in the blood of young (15.76±0.51 nmol/l) and old (16.99±1.1 nmol/l) rats was not significantly different. Morphological signs of BPH were observed in the prostate of both young and old rats. During the induction of BPH in the experiment, according to the level of cfDNA, cell death processes have not changed significantly in young rats but significantly increased in old rats. A similar trend was observed in the group of intact animals. The obtained data indicate that apoptosis processes are enhanced during the development of BPH despite the growth of tissues in the prostate itself.

scholarly journals Insulin resistance for glucose uptake and Akt2 phosphorylation in the soleus, but not epitrochlearis, muscles of old vs. adult rats

2010 ◽  
Vol 108 (6) ◽  
pp. 1631-1640 ◽  
Author(s):  
Naveen Sharma ◽  
Edward B. Arias ◽  
Mini P. Sajan ◽  
James G. MacKrell ◽  
Abhijit D. Bhat ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Ex Vivo ◽  
Brown Norway ◽  
Adult Rats ◽  
Insulin Resistant ◽  
Age Related ◽  
Old Rats ◽  
Fast Twitch

The slow-twitch soleus, but not fast-twitch muscle, of old vs. adult rats has previously been demonstrated to become insulin resistant for in vivo glucose uptake. We probed cellular mechanisms for the age effect by assessing whether insulin resistance for glucose uptake was an intrinsic characteristic of the muscle ex vivo and by analyzing key insulin signaling steps. We hypothesized that isolated soleus and epitrochlearis (fast-twitch) muscles from old (25 mo) vs. adult (9 mo) male Fisher-344 × Brown Norway rats would have insulin resistance for Akt2 Thr308 phosphorylation (pAkt2Thr308), AS160 phosphorylation Thr642 (pAS160Thr642), and atypical PKC (aPKCζ/λ) activity corresponding in magnitude to the extent of insulin resistance for [3H]-2-deoxyglucose (2-DG) uptake. Epitrochlearis insulin-stimulated 2-DG uptake above basal values was unaltered by age, and epitrochlearis pAkt2Thr308, pAS160Thr642, and aPKCζ/λ activity were not significantly different in adult vs. old rats. Conversely, insulin-stimulated 2-DG uptake by the soleus of old vs. adult rats was reduced with 1.2 nM (42%) and 30 nM (28%) insulin concomitant with an age-related decline in pAkt2Thr308 of the insulin-stimulated soleus. There were no age effects on pAS160Thr642 or aPKCζ/λ activity or abundance of Akt2, AS160, GLUT4 or Appl1 protein in either muscle. The results suggest the possibility that an age-related decline in pAkt2Thr308, acting by a mechanism other than reduced pAS160Thr642, may play a role in the insulin resistance in the soleus of old rats. Skeletal muscle insulin resistance in old age is distinctive compared with other insulin-resistant rodent models that are not selective for greater insulin resistance in the soleus vs. the epitrochlearis.

scholarly journals INFLUENCE OF ATP-LONG AND MOLSIDOMINE COMBINATION ON THE BIOELECTRIC ACTIVITY OF THE MYOCARDIAL OF YOUNG AND OLD RATS IN CHRONIC SOFT STRESS

2021 ◽  
pp. 5-11
Author(s):  
Liana Kuprash ◽  
Ludmila Sharabura ◽  
Tetyana Panteleymonova ◽  
Svitlana Hudarenko ◽  
Nina Sykalo ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Negative Impact ◽  
Circulatory System ◽  
Stress Factors ◽  
Bioelectrical Activity ◽  
Young Rats ◽  
Adaptive Capabilities ◽  
Age Related ◽  
Male Wistar Rats ◽  
Old Rats

Introduction. Age-related changes in the cardiovascular system lead to a decrease in its reserve adaptive capabilities and an increase in the likelihood of developing diseases under stress and overstrain. A number of experiments have proven the significant role of emotional overstrain and stress in the development of cardiovascular diseases. The high incidence of the circulatory system, the long course and severity of diseases in elderly and old people determine the relevance of the search for treatment using effective and safe drugs. Aim: iinvestigate the effect of a combination of ATP-LONG and molsidomine on the functional state of the myocardium of young and old rats under chronic soft stress. Materials and methods. In experiments on young (10 months) and old (24 months) male Wistar rats, the cardiotropic and cardioprotective activity of the combination of the metabolic cardioprotector ATP-LONG and the vasodilator molsidomine was studied under conditions of chronic soft stress. Results. The negative impact of chronic soft stress on the bioelectrical activity of the myocardium – a violation of the processes of repolarization, conduction and contractility of the heart was found in young rats. The combination of ATP-LONG and molsidomine normalized the bioelectrical activity of the myocardium and increased its resistance to stress factors. In old rats under the influence of chronic stress, signs of impaired repolarization and electrical instability of the heart were more significant than in young animals. The combination ATP-LONG and molsidomine prevented the damaging effect of chronic stress and contributed to the normalization of the electrophysiological parameters of the myocardium of old rats. Conclusions. The results of experiments indicate the pharmacological cardiotropic activity of the combination of ATPLONG and molsidomine in young and old rats with chronic soft stress. Keywords: young rats, old rats, chronic soft stress, myocardium, electrocardiogram, bioelectrical activity of the heart, ATP-LONG, molsidomine, cardioprotective effect.

Differential adrenergic regulation of rat pineal cyclic AMP production and N-acetyltransferase activity during postnatal development: involvement of G alpha s and G alpha i1-2 proteins

1997 ◽  
Vol 155 (2) ◽  
pp. 305-312
Author(s):  
A Harmouch ◽  
JM Guerrero ◽  
D Pozo ◽  
M Rafii-el-Idrissi ◽  
RJ Reiter ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Postnatal Development ◽  
Adrenergic Receptors ◽  
Beta Adrenergic Receptors ◽  
Adult Rats ◽  
Beta Adrenergic ◽  
Young Rats ◽  
Old Rats ◽  
Gs Alpha ◽  
Rat Pineal Gland

We have studied why rat pineal N-acetyltransferase (NAT) activity is relatively insensitive to isoproterenol in young rats when compared with adult rats. We report that activation by isoproterenol of pineal cyclic AMP production and NAT activity is higher in adult than in 2-week-old rats. However, the effect of dibutyryl cyclic AMP, which enters the pinealocyte and duplicates the effect of cyclic AMP, on NAT activity was similar at both ages. Moreover, we found that both alpha- and beta-adrenergic receptors are highly specific at both ages, since the binding of the specific radioligands used to their receptors could be displaced only by their corresponding agonists and antagonists. However, we observed differences between pineals from young and adult rats when several families of the alpha subunit of G-proteins were studied in cell membranes. ADP-ribosylation and immunoblot studies have shown clear differences in both 42 and 45 kDa forms of the Gs alpha Both forms exhibit low values in pineals from 2-week-old animals when compared with 6-week-old. We also show that the later appearance of both Gs alpha forms is roughly similar to the potent activation of cyclic AMP production and NAT activity in adult rats when compared with young rats. In conclusion, the results presented suggest that the relative lack of sensitivity of rat pineal gland to beta-adrenergic receptor agonists early in the postnatal development may be explained by the low levels of membrane Gs alpha, rather than postreceptor-mediated mechanisms or changes in the characteristics of the beta-adrenergic receptors on the pinealocyte membrane.

Maturation of renal and hepatic monodeiodination of thyroxine to triiodothyronine and post-natal changes of serum thyroid hormones in young rats

1982 ◽  
Vol 99 (4) ◽  
pp. 540-545 ◽  
Author(s):  
Yukichi Suzuki ◽  
Kyoko Kita ◽  
Yasuko Uchigata ◽  
Ikuro Takata ◽  
Tamotu Sato
Keyword(s):  
Neonatal Period ◽  
Physiological Role ◽  
Maximal Activity ◽  
Adult Rats ◽  
Young Rats ◽  
Old Rats ◽  
Serum Thyroid Hormone ◽  
Thyroid Hormone Levels ◽  
Serum Thyroid Hormones ◽  
Low Activity

Abstract. Maturational changes of renal and hepatic 5′-monodeiodination of thyroxine (T4) and post-natal changes of serum thyroid hormone levels were investigated in young rats under 35 days of age. Renal T3 generation in the 1-day-old rats was low, rose progressively to a level of more than 200% of the adult rats on days 21 and 28 and declined thereafter. In contrast, hepatic T3 generation increased from an initial low activity to a plateau after 7 days of age, which was 1½ times higher than that of adult rats. Because of the extremely low value of serum T4 in the neonatal period, T3/T4 and rT3/T4 ratios were elevated on day 7. The ratio of rT3/T4 decreased gradually and became stable after 21 days of age, while the T3/T4 ratio increased reciprocally to a peak on days 21 and 28, corresponding to the period of maximal activity of renal T4 monodeiodination. These results indicate that in addition to elevated hepatic T4 monodeiodination, renal conversion of T4 to T3 may play a significant physiological role during the period of enhanced T3 requirement for maturation.

The production of antibodies by young rats

1957 ◽  
Vol 147 (926) ◽  
pp. 140-144 ◽  
Keyword(s):  
Active Immunization ◽  
Protein Fractions ◽  
Antibody Activity ◽  
Adult Rats ◽  
Marked Rise ◽  
Suckling Rats ◽  
Young Rats ◽  
Salmonella Pullorum ◽  
Old Rats

Suckling rats can produce specific agglutinins to Salmonella pullorum during the period when normally γ -globulin is being absorbed from the milk. This production of antibody is as efficient in rats prevented from suckling their mothers as it is in litter-mates suckling normally. The titres of young rats passively immunized by suckling mothers hyperimmune to Salm . pullorum show a decline between 18 and 24 days of age paralleling the decline of more than 80% in the concentration of serum γ -globulin which is known to take place over this period. Yet the titres of actively immunized young rats rise over the same period. These results suggest that the antibody produced by the active immunization is concentrated in the β -globulin, since this alone shows a marked rise during the period. It is known that the antibody activity in adult rats hyperimmunized against Salm . pullorum is concentrated in the γ -globulin. The results of the examination of electrophoretically separated protein fractions of the sera from actively immunized 24-day-old rats support this conclusion, as the bulk of the antibody was found to be present in those fractions which contained β -globulin. Evidence of the production of γ -globulin by the suckling rat was also obtained, however, because of the presence of a small but significant amount of antibody in a fraction containing only γ -globulin.

scholarly journals Effects of short- and long-term feeding of L-carnitine and congeners on the production of eicosanoids from rat peritoneal leucocytes

1994 ◽  
Vol 72 (5) ◽  
pp. 785-793 ◽  
Author(s):  
Ingrid M. Garrelds ◽  
Graham R. Elliott ◽  
Freek J. Zijlstra ◽  
Iván L. Bonta
Keyword(s):  
Term Treatment ◽  
Short Term ◽  
Young Rats ◽  
Long Term Treatment ◽  
Prostaglandin F ◽  
Old Rats ◽  
Short And Long Term ◽  
Propionyl Carnitine ◽  
In Cells

The effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine and L-propionyl carnitine on the production of eicosanoids front in vitro stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both young (4 weeks) and old (18 months) rats were used. A lower number of cells was isolated from the peritonea of treated than control young rats after 4 d feeding, but after 60 d no differences were observed. A similar reduction in cell number was found when old animals were given L-acetyl carnitine or L-propionyl carnitine (acutely) or L-acetyl carnitine or L-carnitine (chronically). Plasma carnitine levels were higher in young rats given carnitine both chronically and acutely. Carnitine derivatives were without effect. In contrast, levels of total carnitine in the plasma of old rats given L-carnitine and L-acetyl carnitine for 4 d and 60 d were higher than in controls. There was no correlation between total plasma carnitine level and effects on prostaglandin, thromboxane and leukotriene B4 (LTB4) production. In young rats the most important changes were observed in relation to the production of prostacyclin (PGI2), measured as 6 keto-prostaglandin Flα. Prostacyclin production was higher in the groups given carnitine or its derivatives. The net result of the changes in PGI2 was that the 6 keto-prostaglandin F1α: thromboxane B2 and the 6 keto-prostaglandin Flα:LTB4 ratios tended to be higher in cells from young animals following short-term feeding with L-carnitine. When young rats were given carnitine compounds for 60 d PGI2 production was lower in cells from L-acetyl carnitine- and L-propionyl carnitine-fed animals. The net result of the changes in PGI2 was that the 6 keto-prostaglandin F1α: thromboxane B2 and the 6 keto-prostaglandin F1α:LTB4 ratios were lower in cells from animals fed with carnitine compounds. In old rats the PGI2 production was lower after short-term feeding with carnitine compounds and was higher after long-term feeding. LTB4 production was lower after L-carnitine and L-acetyl carnitine treatment for 4 d and also lower after 60 d treatment with L-acetyl carnitine. The net results of the changes in PGI2 were that the 6 keto-prostaglandin F1α: thromboxane B2 and the 6 keto-prostaglandin F1α:LTB4 ratios were lower after short-term feeding of all three compounds and higher after the long-term treatment with L-acetyl carnitine and L-propionyl carnitine in old rats. By long-term treatment with low-dose aspirin of patients with heart failure and claudication, the 6 keto-prostaglandin F1α: thromboxane B2 ratio is positively increased, which is a beneficial cardioprotective effect. The mechanism of action of carnitine in heart failure and claudication could also be achieved by an increase of this ratio. Our results suggest that elderly patients could be treated chronically by carnitine to obtain this beneficial effect.

Association of insulin-like growth factor mRNA expressions with muscle regeneration in young, adult, and old rats

1997 ◽  
Vol 273 (1) ◽  
pp. R353-R358 ◽  
Author(s):  
D. R. Marsh ◽  
D. S. Criswell ◽  
M. T. Hamilton ◽  
F. W. Booth
Keyword(s):  
Young Adult ◽  
Growth Factor ◽  
Mrna Expression ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Insulin Like Growth Factor ◽  
Adult Rats ◽  
Young Rats ◽  
Igf I ◽  
Old Rats

The purpose of this study was to determine whether impaired regeneration of skeletal muscle in old rats can be attributed to diminished expression of insulin-like growth factor (IGF) mRNAs. Fischer 344 male rats aged 2 (young), 12 (adult), and 24 mo (old) were given an injection of the myotoxic anesthetic, bupivacaine, into the left tibialis anterior muscle. Muscle mass and protein concentration recovered to contralateral control values by 28 days in young, but not adult or old rats. The temporal and maximal expressions of IGF-I mRNA were similar during recovery from bupivacaine on days 5 and 10 in young, adult, and old rat muscles. IGF-I mRNA levels were reduced toward control levels in young rats by 15 days, but remained elevated in adult and old rats. IGF-I receptor mRNA in bupivacaine-injected muscle of old rats was elevated significantly higher than injected muscle of young and adult rats at recovery day 5. Five days after bupivacaine injection, IGF-II mRNA was increased 46-fold in young rats but was only increased fourfold in adult rats. Thereafter, IGF-II mRNA expression was similar for young, adult, and old rats at 10 and 15 days of recovery. In summary, we demonstrate that impaired regeneration of the tibialis anterior muscle in adult or old rats after bupivacaine-induced damage is associated with a prolonged elevation of IGF-I mRNA expression and/or diminished initial IGF-II mRNA expression.

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