Differences in lung glutathione metabolism may account for rodent susceptibility in elastase-induced emphysema development

2009 ◽  
Vol 296 (4) ◽  
pp. R1113-R1123 ◽  
Author(s):  
Gisella R. Borzone ◽  
Leonel F. Liberona ◽  
Andrea P. Bustamante ◽  
Claudia G. Saez ◽  
Pablo R. Olmos ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Glutathione Reductase ◽  
Diffuse Alveolar Damage ◽  
Intratracheal Instillation ◽  
Glutathione Metabolism ◽  
Oxidized Glutathione ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Glutamylcysteine Synthetase ◽  
Gsh Metabolism

Syrian Golden hamsters develop more severe emphysema than Sprague-Dawley rats after intratracheal instillation of the same dose of elastase/body weight. Although species variations in antielastase defenses may largely explain these results, other variables, such as differences in lung antioxidants, cannot be overlooked since oxidative stress modulates antiprotease activity. We propose that elastase instillation might affect lung glutathione (GSH) metabolism differently in these species. Our aim was to study in hamsters and rats, lung glutathione metabolism at different times, from the stage of diffuse alveolar damage to advanced emphysema. We measured total and oxidized glutathione content as well as activity and expression of enzymes related to GSH synthesis and redox cycling: γ-glutamylcysteine synthetase, glutathione peroxidase, and glutathione reductase. Whereas rats showed no significant changes in these measurements, hamsters showed significant derangement in GSH metabolism early after elastase instillation: 25% fall in total GSH ( P < 0.05) with no increase in oxidized glutathione associated with reduced enzyme activities 24 h after elastase [60% for γ-glutamylcysteine synthetase ( P < 0.01), 30% for glutathione peroxidase ( P < 0.01), and 75% for glutathione reductase ( P < 0.001)]. GSH homeostasis was restored at the end of the first week, involving transient increased expression of these enzymes. We conclude that elastase induces significant alterations in GSH metabolism of hamster lungs and no overall change in rat lungs. Although differences in disease severity may account for our findings, the hamster becomes vulnerable to functional inhibition of α1-antitrypsin by oxidants and thus, even more susceptible to injury than it would be, considering only its low α1-antitrypsin level.

Bioavailability in Vivo of Benzo[a]Pyrene Adsorbed to Diesel Particulate

1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio
Keyword(s):  
Health Risks ◽  
Quantitative Description ◽  
Intratracheal Instillation ◽  
Direct Analysis ◽  
Sprague Dawley ◽  
Reasonable Estimate ◽  
Diesel Particulate ◽  
Sprague Dawley Rats

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.

Glutathione metabolism in heart and liver of the aging rat

1994 ◽  
Vol 72 (1-2) ◽  
pp. 58-61 ◽  
Author(s):  
M. Stio ◽  
T. Iantomasi ◽  
F. Favilli ◽  
P. Marraccini ◽  
B. Lunghi ◽  
...  
Keyword(s):  
Rat Heart ◽  
Reduced Glutathione ◽  
Age Groups ◽  
Glutathione Metabolism ◽  
Oxidized Glutathione ◽  
Glutathione S Transferase ◽  
Age Related ◽  
Glutamylcysteine Synthetase ◽  
Old Rats ◽  
Glucose 6 Phosphate Dehydrogenase

A comprehensive study on glutathione metabolism in rat heart and liver as a function of age was performed. In the heart, reduced glutathione, total glutathione, and the glutathione redox index showed a decrease during aging, while oxidized glutathione levels increased in 5-month-old rats with respect to the young animals and remained quite constant in 14- and 27-month-old rats. In the liver, the highest levels of reduced glutathione were found in the 2-month-old rats, while oxidized glutathione reached a peak at 5 months. Glutathione-associated enzymes showed age-related changes. Glutathione peroxidase, unaffected by aging in the heart, decreased in the liver of the 27-month-old rats. In the heart and the liver, the highest values of glutathione S-transferase were found at 5 months and 27 months, respectively. Glucose-6-phosphate dehydrogenase followed a similar trend in both heart and liver. Glutathione reductase also showed the same behaviour in heart and in liver, increasing in old rats with respect to the other age groups. A decrease in γ-glutamylcysteine synthetase was found in the heart and liver of 27-month-old rats in comparison with the 2-month-old ones. In conclusion, a decreased antioxidant capability has been demonstrated in both heart and liver of old rats.Key words: glutathione metabolism, age, rat heart, rat liver.

Interleukin-1-induced nitric oxide production modulates glutathione synthesis in cultured rat hepatocytes

1996 ◽  
Vol 271 (3) ◽  
pp. C851-C862 ◽  
Author(s):  
P. C. Kuo ◽  
K. Y. Abe ◽  
R. A. Schroeder
Keyword(s):  
Nitric Oxide ◽  
Steady State ◽  
Glutathione Peroxidase ◽  
Glutathione Reductase ◽  
Gene Transcription ◽  
Interleukin 1 ◽  
Rat Hepatocytes ◽  
Glutamylcysteine Synthetase ◽  
Cultured Rat Hepatocytes ◽  
Rate Limiting

In cultured rat hepatocytes, we have previously demonstrated that inhibition of interleukin-1 (IL-1)-mediated nitric oxide (NO) synthesis is associated with depletion of intracellular reduced glutathione (GSH) in toxin-mediated oxidative injury. To further examine NO's effects on GSH metabolism in rat hepatocytes, IL-1-mediated NO synthesis was examined in the context of 1) cysteine, cystine, and methionine uptake; 2) gene transcription and enzyme activities for gamma-glutamylcysteine synthetase, the rate-limiting enzyme in GSH synthesis, glutathione reductase, and glutathione peroxidase; and 3) GSH and oxidized glutathione (GSSG) levels. Inhibition of NO synthesis decreased the GSH content and GSH/GSSG ratio in a guanylyl cyclase-independent fashion. Enzyme activity and steady-state levels of mRNA for gamma-glutamylcysteine synthetase were also depressed. Nuclear run-on analysis demonstrated ablation of gamma-glutamylcysteine synthetase gene transcription. Hepatocellular uptake of cysteine, cystine, and methionine was not altered. Activity and steady-state mRNA levels for glutathione reductase and glutathione peroxidase were not affected. These results indicate that IL-1-mediated NO synthesis regulates hepatocyte GSH synthesis through a mechanism that is dependent on transcriptional regulation of the rate-limiting enzyme in GSH synthesis. In the setting of oxidative stress and IL-1 exposure, hepatocyte synthesis of NO may be protective through regulation of GSH synthesis.

Response of the rat erythrocyte to ozone exposure

1978 ◽  
Vol 45 (6) ◽  
pp. 893-898 ◽  
Author(s):  
E. C. Larkin ◽  
S. L. Kimzey ◽  
K. Siler
Keyword(s):  
Superoxide Dismutase ◽  
Glutathione Peroxidase ◽  
Ozone Exposure ◽  
Sprague Dawley ◽  
Ultrastructural Studies ◽  
Sprague Dawley Rats ◽  
Rubidium Influx ◽  
Potassium Influx ◽  
Time Periods ◽  
Differential Counts

Sprague-Dawley rats were exposed to high (6--8 ppm) and moderate (1.5 ppm) amounts of ozone (O3) for various time periods. Response of the rat erythrocyte to ozone was monitored with red blood cell potassium (rubidium) influx studies, with storage stress combined with ultrastructural studies and with levels of erythrocyte glutathione peroxidase and superoxide dismutase. Erythrocytes of rats exposed to O3 showed no significant changes either in their potassium influx or in their glutathione peroxidase and superoxide dismutase activities compared to controls. Erythrocyte differential counts on O3-exposed animals showed significant changes initially as well as following storage stress compared to controls. Rats exposed to 8 ppm O3 for 4 h showed a marked increase in echinocytes. These consistent transformations from discocytes to echinocytes following O3 exposure suggest latent erythrocyte damage has occurred.

scholarly journals Using Phytochemicals to Investigate the Activation of Nicotine Detoxification via Upregulation of CYP2A6 in Animal Models Exposed Tobacco Smoke Condensate by Intratracheal Instillation

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Dayeon Lee ◽  
Seung-Beom Seo ◽  
Hyun Jeong Lee ◽  
Tae-Sik Park ◽  
Soon-Mi Shim
Keyword(s):  
Antioxidant Capacity ◽  
Chlorogenic Acid ◽  
Tobacco Smoke ◽  
A549 Cells ◽  
Intratracheal Instillation ◽  
Root Extract ◽  
Ionization Mass ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tobacco Smoke Condensate

This study examined the efficacy of standardized Smilax china L. root extract (SSCR) containing chlorogenic acid on detoxifying nicotine from tobacco smoke condensate (TSC) in vitro and in vivo. Chlorogenic acid is an identified bioactive component in SSCR by ultraperformance liquid chromatography/photodiode array/electrospray ionization/mass spectroscopy (UPLC/PDA/ESI/MS). HepG2 liver cells and A549 lung cells were carried for measuring ROS and antioxidant enzymes. Sprague-Dawley rats were treated with nicotine by intratracheal instillation (ITI). Cell viabilities by pretreatments of 5, 12.5, and 25, 50 μg SSCR/mL ranged from 41 to 76% in HepG2 and 65 to 95% in A549. Pretreatments of SSCR inhibited TSC-mediated production of reactive oxygen species (ROS) by 8 and 10% in HepG2 and A549 cells, respectively. However, the expression of CAT, SOD1, and AOX1 was downregulated by SSCR in the both cells. The highest conversion of cotinine was observed at 50 μg/mL of SSCR after 120 min of incubation. SSCR upregulated CYP2A6 3-fold in A549 cells regardless of TSC cotreatment. When Sprague-Dawley rats were treated with nicotine by ITI or subjected to SSCR administration for 14 days, the levels of cotinine in urine increased in SSCR treatment only. The cellular level of antioxidant capacity at 10 or 100 mg/kg body weight/day of SSCR treatment was 1.89 and 1.86 times higher than those of nicotine-control. Results suggest that the intake of SSCR can detoxify nicotine by elevating nicotine conversion to cotinine and antioxidant capacity.

Glutathione levels and activities of glutathione metabolism enzymes in patients with schizophrenia: A systematic review and meta-analysis

2019 ◽  
Vol 33 (10) ◽  
pp. 1199-1214 ◽  
Author(s):  
Sakiko Tsugawa ◽  
Yoshihiro Noda ◽  
Ryosuke Tarumi ◽  
Yu Mimura ◽  
Kazunari Yoshida ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Glutathione Reductase ◽  
Enzyme Activities ◽  
Glutathione Metabolism ◽  
First Episode ◽  
Glutathione Synthetase ◽  
Glutathione System ◽  
Glutathione Disulfide ◽  
Total Glutathione ◽  
Metabolism Enzymes

Background:Glutathione is among the important antioxidants to prevent oxidative stress. However, the relationships between abnormality in the glutathione system and pathophysiology of schizophrenia remain uncertain due to inconsistent findings on glutathione levels and/or glutathione-related enzyme activities in patients with schizophrenia.Methods:A systematic literature search was conducted using Embase, Medline, PsycINFO, and PubMed. Original studies, in which three metabolite levels (glutathione, glutathione disulfide, and total glutathione (glutathione+glutathione disulfide)) and five enzyme activities (glutathione peroxidase, glutathione reductase, glutamate-cysteine ligase, glutathione synthetase, and glutathione S-transferase) were measured with any techniques in both patients with schizophrenia and healthy controls, were included. Standardized mean differences were calculated to determine the group differences in the glutathione levels with a random-effects model.Results:We identified 41, 9, 15, 38, and seven studies which examined glutathione, glutathione disulfide, total glutathione, glutathione peroxidase, and glutathione reductase, respectively. Patients with schizophrenia had lower levels of both glutathione and total glutathione and decreased activity of glutathione peroxidase compared to controls. Glutathione levels were lower in unmedicated patients with schizophrenia than those in controls while glutathione levels did not differ between patients with first-episode psychosis and controls.Conclusions:Our findings suggested that there may be glutathione deficits and abnormalities in the glutathione redox cycle in patients with schizophrenia. However, given the small number of studies examined the entire glutathione system, further studies are needed to elucidate a better understanding of disrupted glutathione function in schizophrenia, which may pave the way for the development of novel therapeutic strategies in this disorder.

Sign in / Sign up

Export Citation Format

Share Document