Oxidative stress mechanisms as potential therapeutic targets in chronic kidney disease

Abstract

Chronic kidney disease (CKD) is a gradual loss of kidney function over time, leading to the development of kidney failure. CKD is a consequence of common civilization diseases, such as arterial hypertension and diabetes, as well as primary kidney and urinary tract diseases of various aetiologies. The pathogenesis of CKD is complex, and the ongoing inflammation and increased oxidative stress (OS) in kidney tissues also play a significant role in the CKD pathophysiological description. Hence, attempts are being made to pharmacologically modify these important pathophysiological pathways. This article presents a brief overview of the aetiopathogenesis of OS in the course of CKD and briefly lists the research on the novel compounds with expected OS-alleviating activity in CKD based on their interference with selected pathophysiological pathways (xanthine oxidase inhibitors, nicotinamide adenine dinucleotide phosphate oxidase inhibitors, protein kinase C inhibitors, transforming growth factor β inhibitors, or activators of nuclear factor erythroid 2-related factor 2). StreszczeniePrzewlekła choroba nerek (PChN) to postępująca utrata funkcji nerek, prowadząca do rozwoju niewydolności nerek. Przewlekła choroba nerek stanowi obecnie narastający globalny problem zdrowotny, ponieważ jest następstwem powszechnie występujących chorób cywilizacyjnych, takich jak nadciśnienie tętnicze i cukrzyca, a także pierwotnych chorób nerek i dróg moczowych o różnej etiologii. Patogeneza PChN jest złożona, a wzajemnie podtrzymujące się lokalny stan zapalny i zwiększony stres oksydacyjny w tkankach nerek również odgrywają istotną rolę w opisie patofizjologicznym PChN. W związku z tym podejmowane są próby modulacji farmakologicznej tych ważnych szlaków patofizjologicznych. W artykule przedstawiono zarys etiopatogenezy stresu oksydacyjnego w przebiegu PChN oraz pokrótce wymieniono badania nad nowymi związkami o spodziewanym działaniu łagodzącym wspomniane zaburzenie w wyniku ich ingerencji w patomechanizmy stresu oksydacyjnego (inhibitory oksydazy ksantynowej, inhibitory oksydazy fosforanu dinukleotydu nikotynamidoadeninowego, inhibitory kinazy białkowej C, inhibitory transformującego czynnika wzrostu β lub aktywatory szlaków zależnych od czynnika transkrypcyjnego Nrf2).

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

“…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].…”

A Synopsis of Current Theories on Drug-Induced Nephrotoxicity

“…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.…”

Novel Approaches in Chronic Renal Failure without Renal Replacement Therapy: A Review

“…Additionally, in the presence of chloride ions, H 2 O 2 is catalyzed to hypochlorous acid by myeloperoxidase activity. Excessive ROS can lead to the oxidation of lipids, proteins, and DNA [204,205]. In CKD patients, inflammatory processes and oxidative stress predominate, including increased TNF-α, IL-6, and NF-κB activation, which also alter the immune system and adipose tissue through the production and secretion of adipokines, contributing to a systemic inflammatory state in CKD.…”

“…Glutathione peroxidase reduces H 2 O 2 and other organic peroxides to water and oxygen, requiring glutathione as a hydrogen donor-a scavenger for H 2 O 2 , hydroxyl radicals, and chlorinated oxidants. Decreased levels of glutathione and plasma GP activity have been reported in CKD patients [204,205]. On the other hand, various antioxidants, including vitamin E, vitamin C, curcumin, resveratrol, green tea, and other metabolites, flavonoids, and polyphenols derived from plant species [206], can ameliorate oxidative stress in CKD patients.…”