Cellular and Molecular Mechanisms of Kidney Toxicity

Barnett, Lillie Marie A.; Cummings, Brian S.

doi:10.1016/j.semnephrol.2018.12.004

Cited by 27 publications

(13 citation statements)

References 75 publications

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“…As discussed above, dysfunctional mitochondrial biogenesis, dynamics, or OXPHOS is a vital underlying factor in renal mitochondrial damage [ 11 ]. Although the commonly used drugs, such as cisplatin, gentamycin, cyclosporine A, and doxorubicin, in clinical practice have anticancer, antibiotic, and anti-inflammatory effects, they have irreversible side effects on the kidney [ 225 ]. The current literature suggests that mitochondrial dysfunction adversely alters kidney function and worsens complications that may promote complex renal diseases [ 6 ].…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

The Effect of Polyphenols on Kidney Disease: Targeting Mitochondria

Ashkar

Bhullar

2022

Nutrients

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Mitochondrial function, including oxidative phosphorylation (OXPHOS), mitochondrial biogenesis, and mitochondria dynamics, are essential for the maintenance of renal health. Through modulation of mitochondrial function, the kidneys are able to sustain or recover acute kidney injury (AKI), chronic kidney disease (CKD), nephrotoxicity, nephropathy, and ischemia perfusion. Therapeutic improvement in mitochondrial function in the kidneys is related to the regulation of adenosine triphosphate (ATP) production, free radicals scavenging, decline in apoptosis, and inflammation. Dietary antioxidants, notably polyphenols present in fruits, vegetables, and plants, have attracted attention as effective dietary and pharmacological interventions. Considerable evidence shows that polyphenols protect against mitochondrial damage in different experimental models of kidney disease. Mechanistically, polyphenols regulate the mitochondrial redox status, apoptosis, and multiple intercellular signaling pathways. Therefore, this review attempts to focus on the role of polyphenols in the prevention or treatment of kidney disease and explore the molecular mechanisms associated with their pharmacological activity.

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Section: Discussion and Perspectivesmentioning

confidence: 99%

The Effect of Polyphenols on Kidney Disease: Targeting Mitochondria

Ashkar

Bhullar

2022

Nutrients

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“…It is likely that the oxidative stress in RPTEC cells after 24 h of incubation with cisplatin gradually increased, and in the initial stage, induced the antioxidant response. Low concentrations of ROS are known to activate signaling pathways responsible for the antioxidant defense of cells [ 32 ]. Moreover, intracellular components may interact with cisplatin, resulting in its inactivation [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

The Influence of Betulin and Its Derivatives EB5 and ECH147 on the Antioxidant Status of Human Renal Proximal Tubule Epithelial Cells

Kruszniewska‐Rajs

Strzałka‐Mrozik

Kimsa-Dudek

et al. 2022

IJMS

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Betulin and its derivatives, 28-propyne derivative EB5 and 29-diethyl phosphonate analog ECH147, are promising compounds in anti-tumor activity studies. However, their effect on kidney cells has not yet been studied. The study aimed to determine whether betulin and its derivatives—EB5 and ECH147—influence the viability and oxidative status of human renal proximal tubule epithelial cells (RPTECs). The total antioxidant capacity of cells (TEAC), lipid peroxidation product malondialdehyde (MDA) level, and activity of antioxidant enzymes (SOD, CAT, and GPX) were evaluated. Additionally, the mRNA level of genes encoding antioxidant enzymes was assessed. Cisplatin and 5-fluorouracil were used as reference substances. Betulin and its derivatives affected the viability and antioxidant systems of RPTECs. Betulin strongly reduced TEAC in a concentration-dependent manner. All tested compounds caused an increase in MDA levels. The activity of SOD, CAT, and GPX, and the mRNA profiles of genes encoding antioxidant enzymes depended on the tested compound and its concentration. Betulin showed an cisplatin-like effect, indicating its nephrotoxic potential. Betulin derivatives EB5 and ECH147 showed different impacts on the antioxidant system, which gives hope that these compounds will not cause severe consequences for the kidneys in vivo.

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“…T cells that express choline acetyltransferase then convert choline to ACh, which is then released and stimulates ␣7-nicotinic ACh receptors on macrophages and other inflammatory cells (6). This suppresses their release of cytokines such as TNF-␣ and protects other sites of the body from a variety of inflammatory conditions (7). TRP, transient receptor potential cation channel subfamily; DAMP, damage-associated molecular pattern.…”

Section: Afferent Detection Of Mechanical Stressmentioning

confidence: 99%

“…The subsequent hospitalization and increased risk of chronic kidney disease leads to a high economic burden for both the patient and healthcare systems (35,99,122). Over the past few decades, researchers have gained significant insights into the complex pathophysiology of AKI, including details about the inflammatory response, tubular cell injury and death, and vascular damage (7,46,51,57,104). However, despite these advances, there are still no targeted therapies for this important clinical disorder.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound for the treatment of acute kidney injury and other inflammatory conditions: a promising path toward noninvasive neuroimmune regulation

Cai

Nash

Okusa

2020

American Journal of Physiology-Renal Physiology

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Acute kidney injury (AKI) is an important clinical disorder with high prevalence, serious consequences, and limited therapeutic options. Modulation of neuroimmune interaction by nonpharmacological methods is emerging as a novel strategy for treating inflammatory diseases, including AKI. Recently, pulsed ultrasound (US) treatment was shown to protect from AKI by stimulating the cholinergic anti-inflammatory pathway. Because of the relatively simple, portable, and noninvasive nature of US procedures, US stimulation may be a valuable therapeutic option for treating inflammatory conditions. This review discusses potential impacts of US bioeffects on the nervous system and how this may generate feedback onto the immune system. We also discuss recent evidence supporting the use of US as a means to treat AKI and other inflammatory diseases.

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Cellular and Molecular Mechanisms of Kidney Toxicity

Cited by 27 publications

References 75 publications

The Effect of Polyphenols on Kidney Disease: Targeting Mitochondria

The Effect of Polyphenols on Kidney Disease: Targeting Mitochondria

The Influence of Betulin and Its Derivatives EB5 and ECH147 on the Antioxidant Status of Human Renal Proximal Tubule Epithelial Cells

Ultrasound for the treatment of acute kidney injury and other inflammatory conditions: a promising path toward noninvasive neuroimmune regulation

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