Diabetic Nephropathy: Significance of Determining Oxidative Stress and Opportunities for Antioxidant Therapies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12378 - 12378

Published: Aug. 3, 2023

Diabetes mellitus (DM) belongs to the category of socially significant diseases with epidemic rates increases in prevalence. Diabetic nephropathy (DN) is a specific kind kidney damage that occurs 40% patients DM and considered serious complication DM. Most modern methods for treatments aimed at slowing down progression DN have side effects do not produce unambiguous positive results long term. This fact has encouraged researchers search additional or alternative treatment methods. Hyperglycemia negative effect on renal structures due number factors, including activation polyol hexosamine glucose metabolism pathways, renin-angiotensin-aldosterone sympathetic nervous systems, accumulation advanced glycation end products insulin resistance endothelial dysfunction tissues. The above mechanisms cause development oxidative stress (OS) reactions mitochondrial dysfunction, which turn contribute DN. Modern antioxidant therapies involve various phytochemicals (food antioxidants, resveratrol, curcumin, alpha-lipoic acid preparations, etc.), are widely used only diabetes but also other systemic diseases. It been suggested therapeutic approaches target source reactive oxygen species may certain advantages terms nephroprotection from OS. review describes significance studies OS biomarkers pathogenesis analyzes reducing intensity prevention

Language: Английский

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Diabetes mellitus—Progress and opportunities in the evolving epidemic

Cell, Journal Year: 2024, Volume and Issue: 187(15), P. 3789 - 3820

Published: July 1, 2024

Language: Английский

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Mitochondrial oxidative damage reprograms lipid metabolism of renal tubular epithelial cells in the diabetic kidney

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 11, 2024

Abstract The functional and structural changes in the proximal tubule play an important role occurrence development of diabetic kidney disease (DKD). Diabetes-induced metabolic changes, including lipid metabolism reprogramming, are reported to lead state tubular epithelial cells (TECs), among all disturbances metabolism, mitochondria serve as central regulators. Mitochondrial dysfunction, accompanied by increased production mitochondrial reactive oxygen species (mtROS), is considered one primary factors causing injury. Most studies have discussed how altered flux drives oxidative stress during DKD. In present study, we focused on targeting damage upstream factor abnormalities under conditions TECs. Using SS31, a tetrapeptide that protects cristae structure, demonstrated contributes TEC injury peroxidation caused accumulation. Mitochondria protected using SS31 significantly reversed decreased expression key enzymes regulators fatty acid oxidation (FAO), but had no obvious effect major glucose rate-limiting enzymes. facilitated renal Sphingosine-1-phosphate (S1P) deposition limited elevated Acer1, S1pr1 SPHK1 activity, Spns2 expression. These data suggest unbalanced droplet (LD) formulation, peroxidation, impaired FAO sphingolipid homeostasis An vitro study high drove cytosolic phospholipase A2 (cPLA2), which, turn, was responsible for LD generation S1P accumulation, HK-2 cells. A mitochondria-targeted antioxidant inhibited activation cPLA2f isoforms. Taken together, these findings identify mechanistic links between reprogrammed TECs, provide further evidence nephroprotective effects via influencing pathways.

Language: Английский

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The key role of altered tubule cell lipid metabolism in kidney disease development

Kidney International, Journal Year: 2024, Volume and Issue: 106(1), P. 24 - 34

Published: April 16, 2024

Kidney epithelial cells have very high energy requirements, which are largely met by fatty acid oxidation. Complex changes in lipid metabolism observed patients with kidney disease. Defects oxidation and increased uptake, especially the context of hyperlipidemia proteinuria, contribute to this excess build-up exacerbate disease development. Recent studies also highlighted role de novo lipogenesis fibrosis. The defect causes starvation. Increased synthesis, lower can cause toxic build-up, reactive oxygen species generation, mitochondrial damage. A better understanding these metabolic processes may open new treatment avenues for diseases targeting metabolism.

Language: Английский

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Pathological mechanisms of kidney disease in ageing

Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: 20(9), P. 603 - 615

Published: July 18, 2024

Language: Английский

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Mitochondrial metabolic reprogramming in diabetic kidney disease

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(6)

Published: June 24, 2024

Abstract Diabetic kidney disease, known as a glomerular arises from metabolic disorder impairing renal cell function. Mitochondria, crucial organelles, play key role in substance metabolism via oxidative phosphorylation to generate ATP. Cells undergo reprogramming compensatory mechanism fulfill energy needs for survival and growth, attracting scholarly attention recent years. Studies indicate that mitochondrial significantly influences the pathophysiological progression of DKD. Alterations lead abnormal expression signaling molecules activation pathways, inducing stress-related cellular damage, inflammatory responses, apoptosis, autophagy irregularities, culminating fibrosis insufficiency. This review delves into impact on DKD pathogenesis, emphasizing regulation regulators downstream pathways. Therapeutic interventions targeting can potentially delay progression. The findings underscore importance focusing develop safer more effective therapeutic approaches.

Language: Английский

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

Biomolecules, Journal Year: 2024, Volume and Issue: 14(1), P. 137 - 137

Published: Jan. 22, 2024

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

Language: Английский

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The Interplay between Immune and Metabolic Pathways in Kidney Disease

Cells, Journal Year: 2023, Volume and Issue: 12(12), P. 1584 - 1584

Published: June 8, 2023

Kidney disease is a significant health problem worldwide, affecting an estimated 10% of the global population. encompasses diverse group disorders that vary in their underlying pathophysiology, clinical presentation, and outcomes. These include acute kidney injury (AKI), chronic (CKD), glomerulonephritis, nephrotic syndrome, polycystic disease, diabetic many others. Despite distinct etiologies, these share common feature immune system dysregulation metabolic disturbances. The pathways are intimately connected interact to modulate pathogenesis diseases. responses diseases includes complex interplay between various cell types, including resident infiltrating cells, cytokines, chemokines, complement factors. factors can trigger perpetuate inflammation, causing renal tissue progressive fibrosis. In addition, play critical roles diseases, glucose lipid metabolism, oxidative stress, mitochondrial dysfunction, altered nutrient sensing. Dysregulation contributes progression by inducing tubular injury, apoptosis, Recent studies have provided insights into intricate revealing novel therapeutic targets for prevention treatment Potential strategies modulating through targeting key or inhibiting pro-inflammatory signaling pathways, improving function, nutrient-sensing such as mTOR, AMPK, SIRT1. This review highlights importance potential implications pathways.

Language: Английский

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JAK/STAT signaling in diabetic kidney disease

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Aug. 11, 2023

Diabetic kidney disease (DKD) is the most important microvascular complication of diabetes and leading cause end-stage renal (ESRD) worldwide. The Janus kinase/signal transducer activator transcription (JAK/STAT) signaling pathway, which out balance in context DKD, acts through a range metabolism-related cytokines hormones. JAK/STAT primary node progression DKD. latest research on helps determine role this pathway factors associated with DKD progression. These include renin–angiotensin system (RAS), fibrosis, immunity, inflammation, aging, autophagy, EMT. This review epitomizes progress understanding complicated explanation etiologies discusses whether it can be potential target for treating It further summarizes inhibitors, natural products, other drugs that are promising how these inhibitors alleviate to explore possible will contribute formulating effective treatment strategies near future.

Language: Английский

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Renal-Protective Roles of Lipoic Acid in Kidney Disease

Nutrients, Journal Year: 2023, Volume and Issue: 15(7), P. 1732 - 1732

Published: April 1, 2023

The kidney is a crucial organ that eliminates metabolic waste and reabsorbs nutritious elements. It also participates in the regulation of blood pressure, maintenance electrolyte balance pH homeostasis, as well erythropoiesis vitamin D maturation. Due to such heavy workload, an energy-demanding constantly exposed endogenous exogenous insults, leading development either acute injury (AKI) or chronic disease (CKD). Nevertheless, there are no therapeutic managements treat AKI CKD effectively. Therefore, novel approaches for fighting urgently needed. This review article discusses role α-lipoic acid (ALA) preventing treating diseases. We focus on various animal models by which underlying renoprotective mechanisms ALA have been unraveled. covered include diabetic nephropathy, sepsis-induced injury, renal ischemic unilateral ureteral obstruction, injuries induced folic metals cisplatin, cadmium, iron. highlight common ALA’s protective actions decreasing oxidative damage, increasing antioxidant capacities, counteracting inflammation, mitigating fibrosis, attenuating nephron cell death. these achieves its biological function alleviating improving function. we point out more comprehensive, preclinical, clinical studies will be needed make better agent targeting disorders.

Language: Английский

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