scholarly journals Age-Dependent Accumulation of 8-Oxoguanine in the DNA and RNA in Various Rat Tissues

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ben Nie ◽  
Wei Gan ◽  
Fei Shi ◽  
Guo-Xin Hu ◽  
Lian-Guo Chen ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Rna Degradation ◽  
Rat Tissues ◽  
Sprague Dawley ◽  
Dna And Rna ◽  
Sd Rats ◽  
Age Dependent ◽  
Tissue Specimens ◽  
The Relationship ◽  
The Brain

The relationship between the oxidative damage of nucleic acids and aging of animals was investigated by analyzing the nucleic acids derived from various tissue specimens of naturally aged Sprague-Dawley (SD) rats. For this purpose, we established an accurate and sensitive isotope-diluted LC-MS/MS method to determine the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGsn) in DNA and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) in RNA. An age-dependent increase in oxidative DNA and RNA damage was observed in the various organs examined, including the brain, liver, kidneys, and testes. Similar increases in the 8-oxo-dGsn and 8-oxo-Gsn contents were observed in three parts of the brain, the hippocampus, cerebral cortex, and cerebellum, among which, the values for the hippocampus were always the highest. When the oxidized guanosine metabolites were quantified with urine, a similar age-dependent increase was observed for both 8-oxo-dGsn and 8-oxo-Gsn. However, unlike the results of nucleic acid samples derived from the tissues, the amount of 8-oxo-Gsn was significantly higher compared to that of 8-oxo-dGsn, probably reflecting the fact that RNA degradation occurs more frequently than DNA degradation. Our finding indicates that the amount of urinary 8-oxo-Gsn could be considered as a biomarker for the sensitive measurement of oxidative stress and aging.

Toxicokinetic and Genotoxicity Study of NNK in Male Sprague-Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

2021 ◽  
Author(s):  
Shu-Chieh Hu ◽  
Matthew S Bryant ◽  
Estatira Sepehr ◽  
Hyun-Ki Kang ◽  
Raul Trbojevich ◽  
...  
Keyword(s):  
Human Lung ◽  
Inhalation Exposure ◽  
Systemic Exposure ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sd Rats ◽  
New Information ◽  
Sprague Dawley Rats ◽  
Tissue Specimens

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.

Abstract P189: AT 1 R-Dependent Blood-Brain Barrier Disruption Precedes Neuroinflammation In Age-Dependent Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Kayla M Nist ◽  
Jesse Moreira ◽  
Richard D Wainford
Keyword(s):  
Blood Pressure ◽  
Blood Brain Barrier ◽  
Neural Control ◽  
Brain Barrier ◽  
Sprague Dawley ◽  
Control Center ◽  
Blood Brain Barrier Disruption ◽  
Sd Rats ◽  
Blood Brain ◽  
Age Dependent

AIM: We hypothesized paraventricular nucleus (PVN)-specific blood-brain barrier (BBB) dysfunction and neuroinflammation contribute to hypertension and sympathoexcitation that can be attenuated by an Angiotensin II Type 1 Receptor (AT 1 R)-dependent mechanism in the aging Sprague-Dawley (SD) rat. Methods: Naïve male SD rats aged 3-, 8- and 16-months-old (MO) (N=4-6/gp) were used in the following studies. Separate groups of 16 MO rats were administered losartan (21 days; s.c. 3 mg/kg/day) or hydrochlorothiazide (14 days; s.c. 4 mg/kg/day). Blood pressure (femoral cannulation) and plasma NE (ELISA) were assessed at end of study. In separate groups, BBB dysfunction was assessed via PVN FITC extravasation using intravascular co-infusion of FITC-Dextran (10 kDa) and rhodamine B isothiocyanate-Dextran (70 kDa). IHC/IF was performed in naive and losartan-treated rats for microglia (CD11b/c) and astrocytes (GFAP) in the PVN and subfornical organ (SFO). Results: Male SD rats develop HTN and sympathoexcitation with age. At 8 and 16 MO, rats exhibit PVN BBB dysfunction (increased FITC extravasation). However, only 16 MO rats exhibit significant PVN neuroinflammation (increased microglial activation and astrocyte reactivity). In the SFO, there is no evidence of age-dependent neuroinflammation. Losartan and HCTZ both significantly lower blood pressure to similar levels, however, only losartan significantly attenuates PVN BBB dysfunction and neuroinflammation. Conclusions: Within the PVN, a known neural control center, there are AT 1 R-dependent increases in PVN BBB disruption and neuroinflammation that we speculate contribute to hypertension in aging SD rats.

Abstract P289: Cardio-protective Peptide Ac-SDKP is Highly Concentrated in Lymph Nodes

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Cesar A Romero ◽  
Sonal Vaid ◽  
Nitin Kumar ◽  
Tang-Dong Liao ◽  
Oscar A Carretero
Keyword(s):  
Lymph Node ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Giant Cells ◽  
Rat Tissues ◽  
Cortical Region ◽  
Sprague Dawley ◽  
Beneficial Effects ◽  
Sd Rats ◽  
Natural Peptide

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural peptide released from its precursor Thymosin β4 (Tβ4) by meprin-α and the prolyl oligopeptidase enzymes (POP) in sequential steps. Ac-SDKP is hydrolyzed by the angiotensin converting enzyme (ACE). Ac-SDKP has anti-inflammatory and anti-fibrotic effects in heart, aorta and kidney and part of the beneficial effects of ACE inhibitors has been ascribed to the increased levels of Ac-SDKP. Ac-SDKP is present in spleen and thymus, however, the presence of Ac-SDKP in the lymph node has not been studied. We hypothesized that Tβ4, Ac-SDKP and its releasing enzymes are present in lymph node. Ac-SDKP concentration was evaluated in Sprague-Dawley (SD) rat tissues. Tβ4 as well as Meprin-α and POP enzymes were measured in the lymph node, thymus, spleen and other tissues obtained from SD rats. Additionally, Ac-SDKP content was measured in different cell populations of lymph node obtained through cell sorting. Lymph node showed the highest Ac-SDKP concentration (181±18.3 ng/mg of protein), followed by the testis (104.3±6.5, thymus (54.2±1.8) and spleen (44.9±4.7) in SD rats (P<0.001 lymph node vs. testis, thymus and spleen). Meprin-α and POP activity were present in lymph node, spleen and thymus. Tβ4 and Meprin-α immunostaining were found to be positive in multinucleated giant cells in the cortical region of lymph node and along the septums; it was also found in the follicular region and germinal center. POP staining was found positive in the cortical region. In the lymph node, Ac-SDKP concentration was higher in Macrophages (CD45+CD68+) in comparison with T lymphocytes (CD45+CD3+) (150±110 pmol/100,000 cell vs. 0.3±0.1pmol/100,000cell, respectively). We conclude that in lymph node, Ac-SDKP is highly concentrated and that all the components of Tβ4/Ac-SDKP system are present. Macrophages could be the main source of Ac-SDKP in lymph node. The presence of Ac-SDKP in lymph node may have important implications in understanding inflammation and target organ damage in cardiovascular diseases.

Age-dependent nerve cell loss in the brain of Sprague-Dawley rats: effect of long term acetyl-L-carnitine treatment

1990 ◽  
Vol 10 (2) ◽  
pp. 173-185 ◽  
Author(s):  
P. Napoleone ◽  
F. Ferrante ◽  
O. Ghirardi ◽  
M.T. Ramacci ◽  
F. Amenta
Keyword(s):  
Nerve Cell ◽  
Cell Loss ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Age Dependent ◽  
The Brain

scholarly journals Effects of tiletamine-xylazine-tramadol combination and its specific antagonist on AMPK in the brain of rats

2019 ◽  
Vol 63 (2) ◽  
pp. 285-292
Author(s):  
Ning Ma ◽  
Xin Li ◽  
Hong-bin Wang ◽  
Li Gao ◽  
Jian-hua Xiao
Keyword(s):  
Mrna Expression ◽  
Opposite Effect ◽  
Brain Regions ◽  
Control Group ◽  
Sprague Dawley ◽  
Sd Rats ◽  
The Central Nervous System ◽  
Specific Antagonist ◽  
Sedation And Analgesia ◽  
The Brain

AbstractIntroduction:Tiletamine-xylazine-tramadol (XFM) has few side effects and can provide good sedation and analgesia. Adenosine 5’-monophosphate-activated protein kinase (AMPK) can attenuate trigeminal neuralgia. The study aimed to investigate the effects of XFM and its specific antagonist on AMPK in different regions of the brain.Material and Methods:A model of XFM in the rat was established. A total of 72 Sprague Dawley (SD) rats were randomly divided into three equally sized groups: XFM anaesthesia (M group), antagonist (W group), and XFM with antagonist interactive groups (MW group). Eighteen SD rats were in the control group and were injected intraperitoneally with saline (C group). The rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus, and brain stem were immediately separated, in order to detect AMPKα mRNA expression by quantitative PCR.Results:XFM was able to increase the mRNA expression of AMPKα1 and AMPKα2 in all brain regions, and the antagonist caused the opposite effect, although the effects of XFM could not be completely reversed in some areas.Conclusion:XFM can influence the expression of AMPK in the central nervous system of the rat, which can provide a reference for the future development of anaesthetics for animals.

Differential Effects of Angiotensin II and Angiotensin-(1-7) at the Nucleus Tractus Solitarii of Transgenic Rats with Low Brain Angiotensinogen

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 700-700
Author(s):  
Aurea S Couto ◽  
Ovidiu Baltatu ◽  
Robson A S Santos ◽  
Detlev Ganten ◽  
Michael Bader ◽  
...  
Keyword(s):  
Heart Rate ◽  
Baroreflex Sensitivity ◽  
Renin Angiotensin System ◽  
Nucleus Tractus Solitarii ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Baroreflex Control ◽  
Sd Rats ◽  
The Brain

P42 The potential importance of permanent alteration of the brain renin-angiotensin system on angiotensin (Ang) II and Ang-(1-7) effects at the level of the nucleus tractus solitarii (NTS) was investigated in transgenic rats with a deficit in brain angiotensinogen production TGR(ASrAOGEN) (TGR). Ang II (10 pmol), Ang-(1-7) (10 pmol) or NaCl (0.9%/ 50 nl) were microinjected into the NTS of urethane-anesthetized TGR (n=28) and Sprague-Dawley (SD, n=22) rats. Mean arterial pressure (MAP) and heart rate (HR) were measured via a femoral artery catheter and the baroreflex control of heart rate was evaluated after increases in MAP induced by phenylephrine (baroreflex bradycardia). Ang II microinjections into the NTS of the TGR induced a higher decrease in MAP and HR (-37 ± 5 mmHg and -69 ± 12.5 beats/min, respectively) in comparison with SD rats (-18 ± 1 mmHg and -51 ± 11 beats/min, respectively). In contrast, changes after Ang-(1-7) microinjections into the NTS of TGR (-6 ± 1 mmHg and -13 ± 5 beats/min) were significantly smaller than that induced in SD (-11 ± 2 mmHg and -24 ± 8 beats/min.). The baroreflex sensitivity was accentuated in TGR in comparison to SD rats (0.69 ± 0.06 vs. 0.44 ± 0.03 ms/ mmHg). Ang II microinjection into the NTS produced similar attenuation in the baroreflex bradycardia in both SD (0.28 ± 0.07 vs. 0.5 ± 0.07 ms/ mmHg, before injection) and TGR (0.44 ± 0.1 vs. 0.82 ± 0.1ms/ mmHg, before injection). Ang-(1-7) microinjection elicited a facilitation of the baroreflex bradycardia in SD (0.62 ± 0.1 vs. 0.4 ± 0.03 ms/ mmHg, before injection). However in TGR, baroreflex bradycardia after Ang-(1-7) was not different from saline microinjection. These results indicate that a permanent inhibition of angiotensinogen synthesis in the brain can lead to a functional up-regulation of Ang II receptors. However, the putative Ang-(1-7) receptors seem to be desensitized in the NTS of these transgenic rats. The alterated baroreflex sensitivity, both before and after Ang microinjection, indicates the functionally relevant decrease in brain Ang in TGR and supports differential regulatory mechanisms for the effects of the two Ang peptides.

scholarly journals Fluorescent Nanoparticles Synthesized from DNA, RNA, and Nucleotides

Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2265 ◽  
Author(s):  
Maofei Wang ◽  
Masaki Tsukamoto ◽  
Vladimir G. Sergeyev ◽  
Anatoly Zinchenko
Keyword(s):  
Nucleic Acids ◽  
Fluorescent Nanoparticles ◽  
Fluorescent Product ◽  
Fluorescent Properties ◽  
Dna And Rna ◽  
Biomass Resources ◽  
Fluorescent Nanomaterials ◽  
The Relationship ◽  
Acid Precursor ◽  
Unique Chemical

Ubiquitous on Earth, DNA and other nucleic acids are being increasingly considered as promising biomass resources. Due to their unique chemical structure, which is different from that of more common carbohydrate biomass polymers, materials based on nucleic acids may exhibit new, attractive characteristics. In this study, fluorescent nanoparticles (biodots) were prepared by a hydrothermal (HT) method from various nucleic acids (DNA, RNA, nucleotides, and nucleosides) to establish the relationship between the structure of precursors and fluorescent properties of biodots and to optimize conditions for preparation of the most fluorescent product. HT treatment of nucleic acids results in decomposition of sugar moieties and depurination/depyrimidation of nucleobases, while their consequent condensation and polymerization gives fluorescent nanoparticles. Fluorescent properties of DNA and RNA biodots are drastically different from biodots synthesized from individual nucleotides. In particular, biodots synthesized from purine-containing nucleotides or nucleosides show up to 50-fold higher fluorescence compared to analogous pyrimidine-derived biodots. The polymeric nature of a precursor disfavors formation of a bright fluorescent product. The reported effect of the structure of the nucleic acid precursor on the fluorescence properties of biodots should help designing and synthesizing brighter fluorescent nanomaterials with broader specification for bioimaging, sensing, and other applications.

scholarly journals Thymomas and Associated Hyperplastic Lesions in Wistar Hannover Rats

2019 ◽  
Vol 47 (2) ◽  
pp. 129-137 ◽  
Author(s):  
Yuki Tomonari ◽  
Junko Sato ◽  
Tetsuro Kurotaki ◽  
Yumi Wako ◽  
Takeshi Kanno ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Benign Tumor ◽  
Sprague Dawley ◽  
Thymic Involution ◽  
Histological Features ◽  
Sd Rats ◽  
Histological Difference ◽  
Morphological Differences ◽  
Relationship Of ◽  
The Relationship

Thymomas occur prevalently in aged Wistar Hannover (WH) rats, along with hyperplastic lesions that cannot be categorized as thymomas. We compared the histological features of hyperplastic lesions and thymomas in WH rats, the incidences of these lesions, and the relationship of these lesions to the degree of thymic involution and also compared these lesions with those of Sprague Dawley (SD) rats in 4-, 13-, 26-, and 104-week studies. There were no morphological differences between hyperplastic cells and benign tumor cells in thymomas. The histological difference between hyperplastic lesions and thymomas was the size of the proliferative areas and the number of medullary differentiation areas. The hyperplastic lesions of the thymus in WH rats might have a potential for progression to thymomas due to the observed multiple hyperplastic lesions or mixed lesions with thymomas. The incidence of these proliferative lesions in the thymus was higher in females than in males. Further, the incidence of these proliferative lesions was higher in WH rats than in SD rats. Thymic involution was more severe in males than in females and more severe in SD rats than in WH rats. The differences in involution progression may have been reflected in the incidence of thymic proliferative lesions in SD and WH rats.

scholarly journals Nitrosamine-induced carcinogenesis. The alkylation of nucleic acids of the rat by N-methyl-N-nitrosourea, dimethylnitrosamine, dimethyl sulphate and methyl methanesulphonate

1968 ◽  
Vol 110 (1) ◽  
pp. 39-47 ◽  
Author(s):  
P. F. Swann ◽  
P. N. Magee
Keyword(s):  
Nucleic Acids ◽  
Dimethyl Sulphate ◽  
Specific Radioactivity ◽  
The Other ◽  
Striking Difference ◽  
Organ Distribution ◽  
Time Intervals ◽  
Dna And Rna ◽  
Cellular Components ◽  
The Brain

1. N[14C]-Methyl-N-nitrosourea, [14C]dimethylnitrosamine, [14C]dimethyl sulphate and [14C]methyl methanesulphonate were injected into rats, and nucleic acids were isolated from several organs after various time-intervals. Radioactivity was detected in DNA and RNA, partly in major base components and partly as the methylated base, 7-methylguanine. 2. No 7-methylguanine was detected in liver DNA from normal untreated rats. 3. The specific radioactivity of 7-methylguanine isolated from DNA prepared from rats treated with [14C]dimethylnitrosamine was virtually the same as that of the dimethylnitrosamine injected. 4. The degree of methylation of RNA and DNA produced in various organs by each compound was determined, and expressed as a percentage of guanine residues converted into 7-methylguanine. With dimethylnitrosamine both nucleic acids were considerably more highly methylated in the liver (RNA, about 1% of guanine residues methylated; DNA, about 0·6% of guanine residues methylated) than in the other organs. Kidney nucleic acids were methylated to about one-tenth of the extent of those in the liver, lung showed slightly lower values and the other organs only very low values. N-Methyl-N-nitrosourea methylated nucleic acids to about the same extent in all the organs studied, the amount being about the same as that in the kidney after treatment with dimethylnitrosamine. In each case the RNA was more highly methylated than the DNA. Methyl methanesulphonate methylated the nucleic acids in several organs to about the same extent as N-methyl-N-nitrosourea, but the DNA was more highly methylated than the RNA. Dimethyl sulphate, even in toxic doses, gave considerably less methylation than N-methyl-N-nitrosourea in all the organs studied, the greatest methylation being in the brain. 5. The rate of removal of 7-methylguanine from DNA of kidneys from rats treated with dimethylnitrosamine was compared with the rate after treatment of rats with methyl methanesulphonate. No striking difference was found. 6. The results are discussed in connexion with the organ distribution of tumours induced by the compounds under study and in relation to the possible importance of alkylation of cellular components for the induction of cancer.

scholarly journals Telomere Dynamics Throughout Spermatogenesis

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 525 ◽  
Author(s):  
Heather Fice ◽  
Bernard Robaire
Keyword(s):  
Brown Norway ◽  
Cell Replication ◽  
Sprague Dawley ◽  
Telomere Shortening ◽  
Toxicant Exposure ◽  
Relative Telomere Length ◽  
Sd Rats ◽  
Epididymal Maturation ◽  
Age Dependent ◽  
Pachytene Spermatocytes

Telomeres are repeat regions of DNA that cap either end of each chromosome, thereby providing stability and protection from the degradation of gene-rich regions. Each cell replication causes the loss of telomeric repeats due to incomplete DNA replication, though it is well-established that progressive telomere shortening is evaded in male germ cells by the maintenance of active telomerase. However, germ cell telomeres are still susceptible to disruption or insult by oxidative stress, toxicant exposure, and aging. Our aim was to examine the relative telomere length (rTL) in an outbred Sprague Dawley (SD) and an inbred Brown Norway (BN) rat model for paternal aging. No significant differences were found when comparing pachytene spermatocytes (PS), round spermatids (RS), and sperm obtained from the caput and cauda of the epididymis of young and aged SD rats; this is likely due to the high variance observed among individuals. A significant age-dependent decrease in rTL was observed from 115.6 (±6.5) to 93.3 (±6.3) in caput sperm and from 142.4 (±14.6) to 105.3 (±2.5) in cauda sperm from BN rats. Additionally, an increase in rTL during epididymal maturation was observed in both strains, most strikingly from 115.6 (±6.5) to 142 (±14.6) in young BN rats. These results confirm the decrease in rTL in rodents, but only when an inbred strain is used, and represent the first demonstration that rTL changes as sperm transit through the epididymis.

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