Oxidative stress mechanisms as potential therapeutic targets in chronic kidney disease

Dobrek, Łukasz

doi:10.5114/ms.2022.117714

Cited by 4 publications

(2 citation statements)

References 32 publications

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“…Also, difficulties in comparing the values obtained in a particular study may arise from different epidemiological parameters of the examined groups. Therefore, it is not surprising that the results are inconsistent [28].…”

Section: Discussionmentioning

confidence: 99%

Activities of antioxidant enzymes and concentrations of selected oxidative stress biomarkers in synovial membranes of patients diagnosed with osteoarthritis

Jakubowska¹,

Dobrakowski²,

Ostałowska³

et al. 2023

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Introduction:Osteoarthritis is a chronic degenerative process of multifactor etiology, still largely unexplained. The activity of antioxidant enzymes and concentration of lipid peroxidation products in synovial membrane can be indirectly inferred from its oxidation-reduction status. The role of synovial membrane in the pathogenesis of osteoarthritis is relatively poorly understood, probably due to the difficulties in the acquisition of the material. Aim of the research:We sought to understand the association between osteoarthritis development and the activities of several antioxidant enzymes and levels of selected oxidative stress biomarkers in synovial membranes of osteoarthritic patients. Material and methods:The synovial tissue samples were collected from 67 patients. Of these patients, 48 underwent endoprosthetic total hip replacement due to osteoarthritis (the examined group), while 19 underwent surgical repair of a traumatic femoral neck fracture (the control group). Homogenates of synovial membrane were prepared according to our published method. The biochemical analysis included: activity of copper-zinc superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), concentrations of protein, malondialdehyde (MDA), thiol groups, and total oxidant status (TOS). Results: When comparing the examined group with the control group, the activity of CuZn-SOD was significantly elevated and the activity of GPx and the level of thiol groups were significantly decreased, whereas the activities of GR, CAT, the levels of protein, MDA, and TOS remained unaltered. Conclusions: Osteoarthritis is associated with oxidative stress and altered activities of the antioxidant enzymes in synovial membrane. However, lipid peroxidation seems not to be important for the etiology and development of osteoarthritis. StreszczenieWprowadzenie: Choroba zwyrodnieniowa stawów jest przewlekłym procesem zwyrodnieniowym o wieloczynnikowej etiologii, wciąż niewyjaśnionym. Aktywność enzymów antyoksydacyjnych i stężenie produktów peroksydacji lipidów w błonie maziowej pośrednio wnioskuje o jej stanie oksydacyjno-redukcyjnym. Rola błony maziowej w patogenezie choroby zwyrodnieniowej stawów jest stosunkowo słabo poznana, prawdopodobnie ze względu na trudności w pozyskiwaniu materiału. Cel pracy: Określenie związku między rozwojem choroby zwyrodnieniowej stawów a aktywnością enzymów antyoksydacyjnych i poziomem wybranych biomarkerów stresu oksydacyjnego w błonach maziowych pacjentów z chorobą zwyrodnieniową stawów. Materiał i metody: Próbki tkanki maziowej pobrano od 67 pacjentów. U 48 pacjentów wykonano endoprotezoplastykę stawu biodrowego z powodu choroby zwyrodnieniowej stawów (grupa badana), a u 19 pacjentów -chirurgiczną plastykę urazowego złamania szyjki kości udowej (grupa kontrolna). Homogenaty błony maziowej przygotowano zgodnie z autor-

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Section: Discussionmentioning

confidence: 99%

Activities of antioxidant enzymes and concentrations of selected oxidative stress biomarkers in synovial membranes of patients diagnosed with osteoarthritis

Jakubowska¹,

Dobrakowski²,

Ostałowska³

et al. 2023

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“…The drug also accumulates in the mitochondria of tubular cells and impairs mitochondrial bioenergetics due to the inducement of oxidative stress, and the release of pro-apoptotic factors, which ultimately lead to renal tubular cell death [ 52 , 74 , 75 ]. A detailed description of the basis of oxidative stress is beyond this review and it can be found in some papers focusing on this topic [ 76 , 77 , 78 , 79 ], including one of my previously published reviews [ 80 ]. However, to sum up, it should be concluded that reactive oxidative and nitrosative species contribute to the damage to kidney cell structure and their function, including lipid peroxidation, protein nitration and oxidation, enzyme inactivation, and DNA breaks.…”

Section: The Molecular Basis Of Drug-induced Nephrotoxicity and The R...mentioning

confidence: 99%

A Synopsis of Current Theories on Drug-Induced Nephrotoxicity

Dobrek

2023

Life

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The overriding goal of the treatment of patients is its effectiveness and safety. However, all medications currently being used also exert some adverse pharmaceutical reactions, which may be regarded as an unintended but inevitable cost of pharmacotherapy. The kidney, as the main organ that eliminates xenobiotics, is an organ especially predisposed and vulnerable to the toxic effects of drugs and their metabolites during their excretion from the body. Moreover, some drugs (e.g., aminoglycosides, cyclosporin A, cisplatin, amphotericin B, and others) have a “preferential” nephrotoxicity potential, and their use is associated with an increased risk of kidney damage. Drug nephrotoxicity is, therefore, both a significant problem and a complication of pharmacotherapy. It should be noted that, currently, there is no generally recognized definition of drug-induced nephrotoxicity and no clear criteria for its diagnosis. This review briefly describes the epidemiology and diagnosis of drug-induced nephrotoxicity and characterizes its pathomechanisms, including immunological and inflammatory disturbances, altered kidney blood flow, tubulointerstitial injury, increased lithogenesis–crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. The study also lists the basic drugs with nephrotoxicity potential and provides a short overview of the preventive methods for reducing the risk of drug-related kidney damage developing.

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Kidney Fibrosis and Oxidative Stress: From Molecular Pathways to New Pharmacological Opportunities

Patera,

Gatticchi,

Cellini

et al. 2024

Biomolecules

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Kidney fibrosis, diffused into the interstitium, vessels, and glomerulus, is the main pathologic feature associated with loss of renal function and chronic kidney disease (CKD). Fibrosis may be triggered in kidney diseases by different genetic and molecular insults. However, several studies have shown that fibrosis can be linked to oxidative stress and mitochondrial dysfunction in CKD. In this review, we will focus on three pathways that link oxidative stress and kidney fibrosis, namely: (i) hyperglycemia and mitochondrial energy imbalance, (ii) the mineralocorticoid signaling pathway, and (iii) the hypoxia-inducible factor (HIF) pathway. We selected these pathways because they are targeted by available medications capable of reducing kidney fibrosis, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRAs), and HIF-1alpha-prolyl hydroxylase inhibitors. These drugs have shown a reduction in oxidative stress in the kidney and a reduced collagen deposition across different CKD subtypes. However, there is still a long and winding road to a clear understanding of the anti-fibrotic effects of these compounds in humans, due to the inherent practical and ethical difficulties in obtaining sequential kidney biopsies and the lack of specific fibrosis biomarkers measurable in easily accessible matrices like urine. In this narrative review, we will describe these three pathways, their interconnections, and their link to and activity in oxidative stress and kidney fibrosis.

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Oxidative stress mechanisms as potential therapeutic targets in chronic kidney disease

Cited by 4 publications

References 32 publications

Activities of antioxidant enzymes and concentrations of selected oxidative stress biomarkers in synovial membranes of patients diagnosed with osteoarthritis

Activities of antioxidant enzymes and concentrations of selected oxidative stress biomarkers in synovial membranes of patients diagnosed with osteoarthritis

A Synopsis of Current Theories on Drug-Induced Nephrotoxicity

Kidney Fibrosis and Oxidative Stress: From Molecular Pathways to New Pharmacological Opportunities

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