Hippocampal mitochondrial dysfunction in rat aging

Hippocampus mitochondrial dysfunction with impaired electron transfer and increased oxidative damage was observed upon rat aging. Hippocampal mitochondria of aged (12 mo) and senescent (20 mo) rats showed, compared with young (4 mo) rats, marked decreases in the rate of state 3 respiration with NAD-dependent substrates (32–51%) and in the activities of mitochondrial complexes I (57–73%) and IV (33–54%). The activity of mitochondrial nitric oxide synthase was also decreased, 53–66%, with age. These losses in enzymatic activity were more marked in the hippocampus than in brain cortex or in whole brain. The histochemical assay of mitochondrial complex IV in the hippocampus showed decreased staining upon aging. Oxidative damage, determined as the mitochondrial content of thiobarbituric-acid reactive substances (TBARS) and protein carbonyls, increased in aged and senescent hippocampus (66–74% in TBARS and 48–96% in carbonyls). A significant statistical correlation was observed between mitochondrial oxidative damage and enzymatic activity. Mitochondrial dysfunction with shortage of energy supply is considered a likely cause of dysfunction in aged hippocampus.

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Mitochondrial function and mitochondria-induced apoptosis in an overstimulated rat ovarian cycle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00223.2005 ◽

2005 ◽

Vol 289 (6) ◽

pp. E1101-E1109 ◽

Cited By ~ 24

Author(s):

Ana Navarro ◽

Rafael Torrejón ◽

Manuel J. Bández ◽

José M. López-Cepero ◽

Alberto Boveris

Keyword(s):

Thiobarbituric Acid ◽

Ovarian Cycle ◽

High Rate ◽

Female Rats ◽

Protein Carbonyls ◽

Corpora Lutea ◽

Mitochondrial Nitric Oxide Synthase ◽

Induced Apoptosis ◽

Calculated Fraction ◽

Mitochondrial Oxidative Damage

Female rats were treated with FSH (40 IU/kg) on the first and second diestrus days (D1 and D2) and with LH (40 IU/kg) on the proestrus (P) day to synchronize and maximize ovarian changes. Follicle area increased by 50% from D1 to P, and the estrus (E) phase showed multiple corpora lutea and massive apoptosis. Increased oxygen uptakes (42–102%) were determined in ovary slices and in isolated mitochondria in active state 3 along the proliferation phase (D1-D2-P) that returned to initial values in the E phase. Mitochondrial content and the electron transfer activities of complexes I and IV were also maximal in the P phase (20–79% higher than in D1). Production of NO by mitochondrial nitric oxide synthase (mtNOS), biochemically determined, and the mtNOS functional activity in regulating state 3 oxygen uptake were also maximal at P and 79–88% higher than at D1. The moderately increased rate of NO in the proliferative phase is associated with mitochondrial biogenesis, whereas the high rate of NO generation by mtNOS at phase P appears to trigger mitochondria-dependent apoptosis. The calculated fraction of ovary mitochondria in state 3 was at a minimal value at the P phase. Mitochondrial oxidative damage, with increased thiobarbituric acid-reactive substances and protein carbonyls, indicates progressive mitochondrial dysfunction between phases P and E. The roles of mitochondria as ATP provider, as a source of NO to signal for mitochondrial proliferation and mitochondria-dependent apoptosis, and as a source of O2− and H2O2 appear well adapted to serve the proliferation-apoptosis sequence of the ovarian cycle.

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The mitochondrial energy transduction system and the aging process

AJP Cell Physiology ◽

10.1152/ajpcell.00213.2006 ◽

2007 ◽

Vol 292 (2) ◽

pp. C670-C686 ◽

Cited By ~ 436

Author(s):

Ana Navarro ◽

Alberto Boveris

Keyword(s):

Nitric Oxide ◽

Electron Transfer ◽

Mitochondrial Dysfunction ◽

Oxidation Products ◽

Mitochondrial Content ◽

Inner Membrane ◽

Rat Brain And Liver ◽

Mitochondrial Nitric Oxide Synthase ◽

Lipid And Protein Oxidation ◽

Oxide Synthase

Aged mammalian tissues show a decreased capacity to produce ATP by oxidative phosphorylation due to dysfunctional mitochondria. The mitochondrial content of rat brain and liver is not reduced in aging and the impairment of mitochondrial function is due to decreased rates of electron transfer by the selectively diminished activities of complexes I and IV. Inner membrane H+ impermeability and F1-ATP synthase activity are only slightly affected by aging. Dysfunctional mitochondria in aged rodents are characterized, besides decreased electron transfer and O2 uptake, by an increased content of oxidation products of phospholipids, proteins and DNA, a decreased membrane potential, and increased size and fragility. Free radical-mediated oxidations are determining factors of mitochondrial dysfunction and turnover, cell apoptosis, tissue function, and lifespan. Inner membrane enzyme activities, such as those of complexes I and IV and mitochondrial nitric oxide synthase, decrease upon aging and afford aging markers. The activities of these three enzymes in mice brain are linearly correlated with neurological performance, as determined by the tightrope and the T-maze tests. The same enzymatic activities correlated positively with mice survival and negatively with the mitochondrial content of lipid and protein oxidation products. Conditions that increase survival, as vitamin E dietary supplementation, caloric restriction, high spontaneous neurological activity, and moderate physical exercise, ameliorate mitochondrial dysfunction in aged brain and liver. The pleiotropic signaling of mitochondrial H2O2 and nitric oxide diffusion to the cytosol seems modified in aged animals and to contribute to the decreased mitochondrial biogenesis in old animals.

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The implication of mitochondrial dysfunction and mitochondrial oxidative damage in di (2-ethylhexyl) phthalate induced nephrotoxicity in both in vivo and in vitro models

Toxicology Mechanisms and Methods ◽

10.1080/15376516.2020.1758980 ◽

2020 ◽

Vol 30 (6) ◽

pp. 427-437

Author(s):

Sorour Ashari ◽

Mohammad Karami ◽

Mohammad Shokrzadeh ◽

Morteza Ghandadi ◽

Nasrin Ghassemi-Barghi ◽

...

Keyword(s):

Oxidative Damage ◽

Mitochondrial Dysfunction ◽

In Vitro Models ◽

Mitochondrial Oxidative Damage ◽

Ethylhexyl Phthalate

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Ginsenoside-Rg1 Protects the Liver against Exhaustive Exercise-Induced Oxidative Stress in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/932165 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 40

Author(s):

Mallikarjuna Korivi ◽

Chien-Wen Hou ◽

Chih-Yang Huang ◽

Shin-Da Lee ◽

Ming-Fen Hsu ◽

...

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

Thiobarbituric Acid ◽

Exhaustive Exercise ◽

Protein Carbonyls ◽

Regular Exercise ◽

Thiobarbituric Acid Reactive Substance ◽

Ginsenoside Rg1 ◽

Exercise Induced ◽

First Time

Despite regular exercise benefits, acute exhaustive exercise elicits oxidative damage in liver. The present study determined the hepatoprotective properties of ginsenoside-Rg1 against exhaustive exercise-induced oxidative stress in rats. Forty rats were assigned into vehicle and ginsenoside-Rg1 groups (0.1 mg/kg bodyweight). After 10-week treatment, ten rats from each group performed exhaustive swimming. Estimated oxidative damage markers, including thiobarbituric acid reactive substance (TBARS) (67%) and protein carbonyls (56%), were significantly (P<0.01) elevated after exhaustive exercise but alleviated in ginsenoside-Rg1 pretreated rats. Furthermore, exhaustive exercise drastically decreased glutathione (GSH) content (∼79%) with concurrent decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. However, these changes were attenuated in Rg1 group. Additionally, increased xanthine oxidase (XO) activity and nitric oxide (NO) levels after exercise were also inhibited by Rg1 pretreatment. For the first time, our findings provide strong evidence that ginsenoside-Rg1 can protect the liver against exhaustive exercise-induced oxidative damage.

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The Classic Methods to Measure Oxidative Damage: Lipid Peroxides, Thiobarbituric-Acid Reactive Substances, and Protein Carbonyls

Oxidative Stress in Aquatic Ecosystems ◽

10.1002/9781444345988.ch32 ◽

2011 ◽

pp. 420-431 ◽

Cited By ~ 5

Author(s):

Volodymyr I. Lushchak ◽

Halyna M. Semchyshyn ◽

Oleh V. Lushchak

Keyword(s):

Oxidative Damage ◽

Lipid Peroxides ◽

Thiobarbituric Acid ◽

Protein Carbonyls ◽

Thiobarbituric Acid Reactive Substances

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Lipoperoxidation and Protein Oxidative Damage Exhibit Different Kinetics During Septic Shock

Mediators of Inflammation ◽

10.1155/2008/168652 ◽

2008 ◽

Vol 2008 ◽

pp. 1-8 ◽

Cited By ~ 23

Author(s):

Max Andresen ◽

Tomas Regueira ◽

Alejandro Bruhn ◽

Druso Perez ◽

Pablo Strobel ◽

...

Keyword(s):

Septic Shock ◽

Vitamin E ◽

Vitamin C ◽

Oxidative Damage ◽

Plasma Protein ◽

Thiobarbituric Acid ◽

Methionine Sulfoxide ◽

Protein Carbonyls ◽

Antioxidant Power ◽

Radical Trapping

Septic shock (SS)-related multiorgan dysfunction has been associated with oxidative damage, but little is known about the temporal damage profile and its relationship to severity. The present work investigated prospectively 21 SS patients. Blood samples were obtained at diagnosis, 24, 72 hours, day 7, and at 3 months. At admission, thiobarbituric acid reactive substances (TBARSs), plasma protein carbonyls, plasma protein methionine sulfoxide (MS), ferric/reducing antioxidant power (FRAP), total red blood cell glutathione (RBCG), uric acid (UA), and bilirrubin levels were increased (P<.05). Total radical—trapping antioxidant potential (TRAP) and vitamin-E were similar to controls, and vitamin-C was decreased (P<.05). During evolution, TBARS and RBCG increased (P<.001), vitamin-E levels remained stable, whereas plasma protein carbonyls and MS, TRAP, vitamin-C, reduced glutathione, and UA levels decreased (P<.006). After 3 months, plasma protein carbonyls and MS persisted elevated. More severe patients exhibited higher TBARS, TRAP, FRAP, vitamin-C, UA, and bilirrubin levels. Our results suggest early and persistent oxidative stress during septic shock and a correlation between increasing levels of lipoperoxidation and sepsis severity.

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Oxidative Damage, Inflammation, and Toll-Like Receptor 4 Pathway Are Increased in Preeclamptic Patients: A Case-Control Study

Oxidative Medicine and Cellular Longevity ◽

10.1155/2012/636419 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 24

Author(s):

Fabiana C. B. Bernardi ◽

Francine Felisberto ◽

Francieli Vuolo ◽

Fabricia Petronilho ◽

Daniela R. Souza ◽

...

Keyword(s):

Inflammatory Response ◽

Oxidative Damage ◽

Thiobarbituric Acid ◽

Protein Carbonyls ◽

Myeloperoxidase Activity ◽

Toll Like Receptor 4 ◽

Protein Levels ◽

Pathway Activation ◽

Control Study

Problem.There was no direct correlation between plasma and placental oxidative damage parameters and inflammation and evidence of TLR4 pathway activation in the placenta in preeclamptic (PE) patients.Method of Study.33 PE patients and 33 normotensive pregnant women were included. The maternal section of the placenta and blood were collected to the determination of oxidative damage markers (thiobarbituric acid reactive species and protein carbonyls), inflammatory response (interleukin-6 and myeloperoxidase activity), and activation of the TLR-4-NF-kB pathway.Results.An increase of IL-6 levels in both plasma and placenta was observed, but myeloperoxidase activity was not significantly different comparing the groups. Oxidative damage parameters were increased in plasma and placenta in PE patients. A significant increase of the protein levels of TLR-4 and NF-kB was observed in the placenta.Conclusion.The TLR4-NF-kB pathway is upregulated in PE, probably generating local and systemic inflammatory response that is followed by local and systemic oxidative damage.

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