Mitochondrial Reactive Oxygen Species and Their Contribution in Chronic Kidney Disease Progression Through Oxidative Stress

Tirichen, Hasna; Yaigoub, Hasnaa; Xu, Wenli; Wu, Changxin; Li, Rongshan; Li, Yafeng

doi:10.3389/fphys.2021.627837

Cited by 199 publications

(141 citation statements)

References 118 publications

(176 reference statements)

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“…Damaged mitochondria are the main source of intracellular ROS due to the decrease in their antioxidant activity [ 42 ]. The effect of C3a on the activity of the mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2), which plays a key role in the mitochondrial defense against ROS production [ 43 ] was evaluated by western blot analysis.…”

Section: Resultsmentioning

confidence: 99%

Shiga Toxin 2 Triggers C3a-Dependent Glomerular and Tubular Injury through Mitochondrial Dysfunction in Hemolytic Uremic Syndrome

Buelli

Locatelli

Carminati

et al. 2022

Cells

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Shiga toxin (Stx)-producing Escherichia coli is the predominant offending agent of post-diarrheal hemolytic uremic syndrome (HUS), a rare disorder of microvascular thrombosis and acute kidney injury possibly leading to long-term renal sequelae. We previously showed that C3a has a critical role in the development of glomerular damage in experimental HUS. Based on the evidence that activation of C3a/C3a receptor (C3aR) signaling induces mitochondrial dysregulation and cell injury, here we investigated whether C3a caused podocyte and tubular injury through induction of mitochondrial dysfunction in a mouse model of HUS. Mice coinjected with Stx2/LPS exhibited glomerular podocyte and tubular C3 deposits and C3aR overexpression associated with cell damage, which were limited by C3aR antagonist treatment. C3a promoted renal injury by affecting mitochondrial wellness as demonstrated by data showing that C3aR blockade reduced mitochondrial ultrastructural abnormalities and preserved mitochondrial mass and energy production. In cultured podocytes and tubular cells, C3a caused altered mitochondrial fragmentation and distribution, and reduced anti-oxidant SOD2 activity. Stx2 potentiated the responsiveness of renal cells to the detrimental effects of C3a through increased C3aR protein expression. These results indicate that C3aR may represent a novel target in Stx-associated HUS for the preservation of renal cell integrity through the maintenance of mitochondrial function.

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Section: Resultsmentioning

confidence: 99%

Shiga Toxin 2 Triggers C3a-Dependent Glomerular and Tubular Injury through Mitochondrial Dysfunction in Hemolytic Uremic Syndrome

Buelli

Locatelli

Carminati

et al. 2022

Cells

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“…The main conclusion of this study is that an absence of robust data to either support or dismiss the hypothesis that inhibition of oxidative stress slows or ameliorates CKD progression has been determined. As a corollary, the role of oxidative stress in CKD progression remains uncertain, despite several authors having suggested its participation in CKD pathophysiology [ 9 , 54 , 56 ]. Future studies need to be optimized with matched data from renal function and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Are Antioxidants Useful in Preventing the Progression of Chronic Kidney Disease?

et al. 2021

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Chronic kidney disease (CKD) is a progressive impairment of renal function for more than three months that affects 15% of the adult population. Because oxidative stress is involved in its pathogenesis, antioxidants are under study for the prophylaxis of CKD progression. The objective of this work was to meta-analyze the efficacy of antioxidant therapy in CKD patients and to identify the most effective candidate antioxidants. Our meta-analysis showed that, despite being quite heterogeneous, overall antioxidant therapy apparently reduced CKD progression. Pentoxifylline and bardoxolone methyl demonstrated a robust and statistically significant protection, while other products showed a favorable but non-significant tendency, due to a high interindividual variability. Off-target (i.e., antioxidant-independent) effects, such as body weight reduction and heart failure-associated blood dilution, might totally or partially explain the protection provided by effective antioxidants. This potential pleiotropy introduces uncertainty on the role of oxidative stress in CKD progression and on antioxidant therapy in its prevention, which needs to be further investigated. Independently, identification of factors determining the nephroprotective effect of each candidate on each patient is thus necessary for a prospectively personalized antioxidant therapy. Finally, pentoxifylline should be further explored for the prophylaxis of CKD progression.

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“…However, in normal circumstances, the renal antioxidant system, including CAT, GPX, and SOD, corrects any ROS-facilitated injury. Renal injury is characterised by the excessive production of mitochondrial ROS [92]. Specific biomolecules undergo oxidation when there is an imbalance in the redox systems, resulting in anatomical and structural modifications of these molecules.…”

Section: Chronic Kidney Disease (Ckd)mentioning

confidence: 99%

Oxidative Stress in Ageing and Chronic Degenerative Pathologies: Molecular Mechanisms Involved in Counteracting Oxidative Stress and Chronic Inflammation

Leyane

Jere

Houreld

2022

IJMS

150

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Ageing and chronic degenerative pathologies demonstrate the shared characteristics of high bioavailability of reactive oxygen species (ROS) and oxidative stress, chronic/persistent inflammation, glycation, and mitochondrial abnormalities. Excessive ROS production results in nucleic acid and protein destruction, thereby altering the cellular structure and functional outcome. To stabilise increased ROS production and modulate oxidative stress, the human body produces antioxidants, “free radical scavengers”, that inhibit or delay cell damage. Reinforcing the antioxidant defence system and/or counteracting the deleterious repercussions of immoderate reactive oxygen and nitrogen species (RONS) is critical and may curb the progression of ageing and chronic degenerative syndromes. Various therapeutic methods for ROS and oxidative stress reduction have been developed. However, scientific investigations are required to assess their efficacy. In this review, we summarise the interconnected mechanism of oxidative stress and chronic inflammation that contributes to ageing and chronic degenerative pathologies, including neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), cardiovascular diseases CVD, diabetes mellitus (DM), and chronic kidney disease (CKD). We also highlight potential counteractive measures to combat ageing and chronic degenerative diseases.

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Mitochondrial Reactive Oxygen Species and Their Contribution in Chronic Kidney Disease Progression Through Oxidative Stress

Cited by 199 publications

References 118 publications

Shiga Toxin 2 Triggers C3a-Dependent Glomerular and Tubular Injury through Mitochondrial Dysfunction in Hemolytic Uremic Syndrome

Shiga Toxin 2 Triggers C3a-Dependent Glomerular and Tubular Injury through Mitochondrial Dysfunction in Hemolytic Uremic Syndrome

Are Antioxidants Useful in Preventing the Progression of Chronic Kidney Disease?

Oxidative Stress in Ageing and Chronic Degenerative Pathologies: Molecular Mechanisms Involved in Counteracting Oxidative Stress and Chronic Inflammation

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