Energy problems in life evolution

Самуилов, В. Д.

doi:10.1007/s10541-005-0107-2

Cited by 15 publications

(7 citation statements)

References 26 publications

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“…Several recent studies have revealed the nephrotoxicity of tenofovir [3-9,18]. Several human and animal studies have shown that TDF is toxic specifically to the proximal tubules, resulting in Fanconi syndrome, characterized by bicarbonate wasting, phosphaturia, amino aciduria, glycosuria, acidosis, and hypophosphatemia.…”

Section: Discussionmentioning

confidence: 99%

“…Because of the deleterious effects of ROS, the cell is equipped with several antioxidants and antioxidant enzyme systems to detoxify ROS produced [18,19]. Oxidative stress is reported to occur in tissues only after the antioxidant (AO) defense mechanisms are depleted, leaving ROS to attack the cellular macromolecules such as lipids, proteins, and DNA.…”

Section: Introductionmentioning

confidence: 99%

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Depletion of the cellular antioxidant system contributes to tenofovir disoproxil fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in the kidney

2013

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BackgroundNephrotoxicity is a dose limiting side effect of tenofovir, a reverse transcriptase inhibitor that is used for the treatment of HIV infection. The mechanism of tenofovir nephrotoxicity is not clear. Tenofovir is specifically toxic to the proximal convoluted tubules and proximal tubular mitochondria are the targets of tenofovir cytotoxicity. Damaged mitochondria are major sources of reactive oxygen species and cellular damage is reported to occur after the antioxidants are depleted. The purpose of the study is to investigate the alterations in cellular antioxidant system in tenofovir induced renal damage using a rat model.ResultsChronic tenofovir administration to adult Wistar rats resulted in proximal tubular damage (as evidenced by light microscopy), proximal tubular dysfunction (as shown by Fanconi syndrome and tubular proteinuria), and extensive proximal tubular mitochondrial injury (as revealed by electron microscopy). A 50% increase in protein carbonyl content was observed in the kidneys of TDF treated rats as compared with the control. Reduced glutathione was decreased by 50%. The activity of superoxide dismutase was decreased by 57%, glutathione peroxidase by 45%, and glutathione reductase by 150% as compared with control. Carbonic Anhydrase activity was decreased by 45% in the TDF treated rat kidneys as compared with control. Succinate dehydrogenase activity, an indicator of mitochondrial activity was decreased by 29% in the TDF treated rat kidneys as compared with controls, suggesting mitochondrial dysfunction.ConclusionTenofovir- induced mitochondrial damage and increased oxidative stress in the rat kidneys may be due to depletion of the antioxidant system particularly, the glutathione dependent system and MnSOD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Depletion of the cellular antioxidant system contributes to tenofovir disoproxil fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in the kidney

2013

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“…Because of the deleterious effects of ROS, the cell is equipped with several enzyme systems to detoxify ROS produced throughout the cell [67,68]. Superoxide dismutases are the major ROS detoxifying enzymes of the cell [69] and catalyze the dismutation of superoxide radicals to hydrogen peroxide and molecular oxygen [70].…”

Section: Mitochondrial Production Of Rosmentioning

confidence: 99%

“…Hydrogen peroxide, while not a radical, is also a ROS, and the cell has developed many enzyme systems to catalyze the decomposition of hydrogen peroxide to water and molecular oxygen [67]. Two forms of peroxiredoxin (PRX) exist in mitochondria [73]: PRX III [86,87] and PRX V [88].…”

Section: Mitochondrial Production Of Rosmentioning

confidence: 99%

Manganese Superoxide Dismutase: Guardian of the Powerhouse

Holley

Bakthavatchalu

Velez-Roman

et al. 2011

IJMS

265

180

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The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS) production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) acting as the chief ROS scavenging enzyme in the cell. Factors that affect the expression and/or the activity of MnSOD, resulting in diminished antioxidant capacity of the cell, can have extraordinary consequences on the overall health of the cell by altering mitochondrial metabolic function, leading to the development and progression of numerous diseases. A better understanding of the mechanisms by which MnSOD protects cells from the harmful effects of overproduction of ROS, in particular, the effects of ROS on mitochondrial metabolic enzymes, may contribute to the development of novel treatments for various diseases in which ROS are an important component.

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“…In the mitochondrial electron transport chain, the ROS superoxide (O 2 •− ) is generated as a byproduct during ATP generation but is also related to the concentration of the electron donor NADH, the local O 2 concentration, and the second-order rate constants for the electron donor and O 2 [14–16]. This is coupled with complex oxidation-reduction (redox) systems that prevent excessive mitochondrial ROS generation and maintain mitochondrial signaling and function [17–20]. For example, mitochondria contain 10% of the cellular GSH pool which can be oxidized to its disulfide form GSSG.…”

Section: Introductionmentioning

confidence: 99%

Alcohol induces mitochondrial redox imbalance in alveolar macrophages

Ling

Harris

Jones

et al. 2013

Free Radical Biology and Medicine

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Alcohol abuse suppresses the immune responses of alveolar macrophages (AMs) and increases the risk of a respiratory infection via chronic oxidative stress and depletion of critical antioxidants within alveolar cells and the alveolar lining fluid. Although alcohol-induced mitochondrial oxidative stress has been demonstrated, the oxidation of the mitochondrial thioredoxin redox circuit in response to alcohol has not been examined. In vitro ethanol exposure of a mouse AM cell line and AMs from an ethanol-fed mice demonstrated NADPH depletion concomitant with oxidation of mitochondrial glutathione and oxidation of the thioredoxin redox circuit system including thioredoxin 2 (Trx2) and thioredoxin 2 reductase (Trx2R). Mitochondrial peroxiredoxins (Prdxs), which are critical for the reduction of the thioredoxin circuit, were irreversibly hyperoxidized to an inactive form. Ethanol also decreased the mRNAs for Trx2, Trx2R, Prdx3, and Prdx5 plus the mitochondrial thiol-disulfide proteins glutaredoxin 2, glutathione reductase, and glutathione peroxidase 2. Thus, the mitochondrial thioredoxin circuit was highly oxidized by ethanol, thereby compromising the mitochondrial antioxidant capacity and ability to detoxify mitochondrial reactive oxygen species. Oxidation of the mitochondrial thioredoxin redox circuit would further compromise the transient oxidation of thiol groups within specific proteins, the basis of redox signaling, and the processes by which cells respond to oxidants. Impaired mitochondria can then jeopardize cellular function of AMs such as phagocytosis which may explain the increased risk of respiratory infection in subjects with an alcohol use disorder.

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Energy problems in life evolution

Cited by 15 publications

References 26 publications

Depletion of the cellular antioxidant system contributes to tenofovir disoproxil fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in the kidney

Depletion of the cellular antioxidant system contributes to tenofovir disoproxil fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in the kidney

Manganese Superoxide Dismutase: Guardian of the Powerhouse

Alcohol induces mitochondrial redox imbalance in alveolar macrophages

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