Neurochemical Research, Год журнала: 2024, Номер 50(1)
Опубликована: Ноя. 22, 2024
Язык: Английский
Physiological Reports, Год журнала: 2024, Номер 12(5)
Опубликована: Фев. 28, 2024
Abstract The role of NRF2 in kidney biology has received considerable interest over the past decade. transcriptionally controls genes responsible for cellular protection against oxidative and electrophilic stress anti‐inflammatory functions. is expressed throughout plays a salt water handling. In disease, animal studies show that protects tubulointerstitial damage reduces interstitial fibrosis tubular atrophy, may slow progression polycystic disease. However, proteinuric glomerular diseases controversial. Although inducer, bardoxolone methyl (CDDO‐Me), increases filtration rate humans, it not been shown to disease diabetic Alport syndrome. Furthermore, was associated with negative effects on fluid retention, proteinuria, blood pressure. Several replicate findings worsened proteinuria more rapid although controversy exists. It clear further study needed better understand kidney. This review summarizes available data clarify promise risks targeting activity
Язык: Английский
Процитировано
12
Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116802 - 116802
Опубликована: Май 24, 2024
Oxidative stress plays a key role in chronic kidney disease (CKD) development and progression, inducing cell damage, inflammation, fibrosis. However, effective therapeutic interventions to slow down CKD advancement are currently lacking. The multifaceted pharmacological effects of molecular hydrogen (H2) have made it promising avenue. H2 is capable capturing harmful •OH ONOO- while maintaining the crucial reactive oxygen species (ROS) involved cellular signaling. NRF2-KEAP1 system, which manages redox balance, could be used treat CKD. activates this pathway, fortifying antioxidant defenses scavenging ROS counteract oxidative stress. can improve NRF2 signaling by using Wnt/β-catenin pathway indirectly activate mitochondria. Additionally, modulates NF-κB activity regulating status, inhibiting MAPK pathways, Trx levels. Treatment with also attenuates HIF neutralizing bolstering HIF-1α function. Furthermore, affects FOXO factors enhances enzymes. Despite encouraging results bench studies, clinical trials still limited require further investigation. focus review on hydrogen's treating renal diseases, specific regulation, discusses its potential applications.
Язык: Английский
Процитировано
10
Journal of Pharmacy and Pharmacology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 20, 2025
Chronic kidney disease (CKD) is a serious health issue with rising morbidity and mortality rates. Despite advances in understanding its pathophysiology, effective therapeutic options are limited, necessitating innovative treatment approaches. Also, current frontline treatments that available against CKD not uniformly often come significant side effects. Therefore, identifying new targets or improving existing for crucial. Drug repurposing promising strategy the drug discovery process involves screening approved drugs applications. This review discusses pharmacological mechanisms clinical evidence support efficacy of these repurposed drugs. Various classes such as inodilators, endothelin-1 type A (ET-1A) receptor antagonists, bisphosphonates, mineralocorticoid (MR) DNA demethylating agents, nuclear factor erythroid 2-related 2 (NRF2) activators, P2X7 inhibitors, autophagy modulators, hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHI) discussed could remarkably contribute CKD. The critically examines potential well-established to slow progression enhance patient outcomes. emphasizes importance multidisciplinary approach advancing field repurposing, ultimately paving way therapies patients suffering from
Язык: Английский
Процитировано
1
Acta Biochimica et Biophysica Sinica, Год журнала: 2024, Номер 56(12), С. 1860 - 1874
Опубликована: Авг. 9, 2024
Diabetic nephropathy (DN) is recognized as one of the primary causes chronic kidney disease and end-stage renal disease. Vaccarin (VAC) confers favorable effects on cardiovascular metabolic diseases, including type 2 diabetes mellitus (T2DM). Nonetheless, potential role mechanism VAC in etiology DN have yet to be completely elucidated. In this study, a classical mouse model T2DM experimentally induced via high-fat diet (HFD)/streptozocin (STZ) regimen. Renal histological changes are assessed H&E staining. Masson staining immunohistochemistry (IHC) employed assess fibrosis. RT-PCR utilized quantify mRNA levels fibrosis, oxidative stress inflammation markers. The malondialdehyde (MDA) reactive oxygen species (ROS), well content glutathione peroxidase (GSH-Px), measured. protein expressions collagen I, TGF-β1, α-SMA, E-cadherin, Nrf2, catalase, SOD3, SOD2, SOD1, p-ERK, p-EGFR (Y845), (Y1173), p-NFκB P65, t-ERK, t-EGFR t-NFκB P65 detected by western blot analysis. Our results reveal that has beneficial effect mice improving function mitigating damage. This achieved through its inhibition inflammatory cytokine overproduction, ROS generation. Moreover, treatment effectively suppresses process epithelial-mesenchymal transition (EMT), crucial characteristic high glucose (HG)-induced HK-2 cells. Network pharmacology analysis molecular docking identify epidermal growth factor receptor (EGFR) target for VAC. Amino acid site mutations Lys-879, Ile-918, Ala-920 EGFR may mediate direct binding EGFR. support these findings, reduces phosphorylation both downstream mediator, extracellular signal-regulated kinase 1/2 (ERK1/2), diabetic kidneys HG-treated Notably, blocking either or ERK1/2 yields benefits similar those observed with treatment. Therefore, study reveals attenuates damage inactivation EGFR/ERK1/2 signaling axis patients.
Язык: Английский
Процитировано
4
Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown
Опубликована: Фев. 12, 2025
Язык: Английский
Процитировано
0
Antioxidants, Год журнала: 2024, Номер 13(4), С. 396 - 396
Опубликована: Март 26, 2024
Chronic hyperglycemia induces intrarenal oxidative stress due to the excessive production of reactive oxygen species (ROS), leading a cascade events that contribute development and progression diabetic kidney disease (DKD). NOX5, pro-oxidant NADPH oxidase isoform, has been identified as significant contributor renal ROS in humans. Elevated levels endothelial cell dysfunction associated inflammation, causing increased permeability, which can disrupt ecosystem, progressive albuminuria fibrosis DKD. This study specifically examines contribution cell-specific human NOX5 expression pathology transgenic mouse model additionally compares with previously characterized oxidase, NOX4, terms their relative roles Regardless NOX4 pathway, this found exacerbates injury, fibrosis. is attributed activation mesenchymal transition (EMT) pathway via enhanced formation modulation redox-sensitive factors. These findings underscore potential therapeutic significance inhibition The proposes inhibiting could be promising approach for mitigating DKD strengthens case NOX5-specific inhibitors intervention.
Язык: Английский
Процитировано
2
Antioxidants, Год журнала: 2024, Номер 13(10), С. 1224 - 1224
Опубликована: Окт. 11, 2024
Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which kidney involvement, so-called nephritis (LN), common and one of the most severe manifestations. Oxidative stress (OS) may play role pathogenesis LN through exacerbation inflammation immune cell dysfunction/dysregulation. Nuclear factor erythroid 2-related 2 (Nrf2), also known as nuclear erythroid-derived 2-like 2, transcription that humans encoded by NFE2L2 gene regarded central regulator antioxidative response. Nrf2-activating compounds have been shown to alleviate oxidative cells tissues lupus-prone mice. Although precise mechanisms Nrf2 activation on system SLE remain be elucidated, are considered novel therapeutical options suppress OS thereby might activity SLE, especially LN. This review therefore summarizes signaling pathway with describes modulating this potential additional clinical interventions.
Язык: Английский
Процитировано
2
Phytomedicine, Год журнала: 2024, Номер 136, С. 156342 - 156342
Опубликована: Дек. 24, 2024
Язык: Английский
Процитировано
2
Molecules, Год журнала: 2024, Номер 29(13), С. 2971 - 2971
Опубликована: Июнь 22, 2024
Elderberry (
Язык: Английский
Процитировано
1
Antioxidants, Год журнала: 2024, Номер 13(10), С. 1156 - 1156
Опубликована: Сен. 24, 2024
The kidney plays a critical role in maintaining the homeostasis of body fluid by filtration metabolic wastes and reabsorption nutrients. Due to overload, vast energy is required through aerobic metabolism, which inevitably leads generation reactive oxygen species (ROS) kidney. Under unstressed conditions, ROS are counteracted antioxidant systems maintained at low levels, involved signal transduction physiological processes. Accumulating evidence indicates that reduction–oxidation (redox) system interacts with renal tubular transport. Redox imbalance or dysfunction transport disease. Here, we discuss outline common feature Importantly, describe key molecules their relationship redox and, finally, summarize impact dysregulation on pathogenesis progression acute chronic
Язык: Английский
Процитировано
1