Pathomechanisms of Diabetic Kidney Disease

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(23), P. 7349 - 7349

Published: Nov. 27, 2023

The worldwide occurrence of diabetic kidney disease (DKD) is swiftly rising, primarily attributed to the growing population individuals affected by type 2 diabetes. This surge has been transformed into a substantial global concern, placing additional strain on healthcare systems already grappling with significant demands. pathogenesis DKD intricate, originating hyperglycemia, which triggers various mechanisms and pathways: metabolic, hemodynamic, inflammatory, fibrotic ultimately lead renal damage. Within each pathway, several mediators contribute development structural functional changes. Some these mediators, such as inflammatory cytokines, reactive oxygen species, transforming growth factor β are shared among different pathways, leading overlap interaction between them. While current treatment options for have shown advancement over previous strategies, their effectiveness remains somewhat constrained patients still experience residual risk progression. Therefore, comprehensive grasp molecular underlying onset progression imperative continued creation novel groundbreaking therapies this condition. In review, we discuss achievements in fundamental research, particular emphasis individual factors recent developments treatment.

Language: Английский

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Urinary biomarkers in diabetic nephropathy

Clinica Chimica Acta, Journal Year: 2024, Volume and Issue: 561, P. 119762 - 119762

Published: June 5, 2024

Language: Английский

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Biomedicine and pharmacotherapeutic effectiveness of combinatorial atorvastatin and quercetin on diabetic nephropathy: An in vitro study

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116533 - 116533

Published: April 3, 2024

Diabetic nephropathy is a type of kidney disorder that develops as complication multifactorial diabetes. characterized by microangiopathy, resulting from glucose metabolism, oxidative stress, and changes in renal hemodynamics. This study strived to evaluate the vitro cytoprotective activity atorvastatin (ATR), quercetin (QCT) alone combination against diabetic nephropathy. The MTT assay was utilized analyze effects test compounds on NRK-52E rat epithelial cells. detection apoptosis ability scavenge free radicals assessed via acridine orange-ethidium bromide (AO-EB) dual fluorescence staining, 2,2-diphenyl-1-picrylhydrazyfree (DPPH), respectively. anti-inflammatory effect western blot analysis TGF-β, TNF-α, IL-6 further determine combinatorial efficacy. Atorvastatin treatment significantly lowered expression indicating protective role Streptozotocin-induced nephrotoxicity. cells treated with showed green fluorescing nuclei AO-EB staining assay, restored cell viability. Quercetin, both atorvastatin, demonstrated strong DPPH radical scavenging encountered an anti-oxidant these drugs. Nevertheless, there currently no existing literature reports QCT renoprotective drug statins context Hence, findings suggest may have clinical potential treating

Language: Английский

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The protective impact of berberine against doxorubicin-induced nephrotoxicity in rats

Tissue and Cell, Journal Year: 2021, Volume and Issue: 73, P. 101612 - 101612

Published: Aug. 3, 2021

Language: Английский

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Glutathione Peroxidase 4 Is a Predictor of Diabetic Kidney Disease Progression in Type 2 Diabetes Mellitus

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 10

Published: Oct. 12, 2022

Background. Diabetic kidney disease (DKD) represents a heavy burden in type 2 diabetes mellitus (T2DM). Ferroptosis plays an important role DKD, and it thus provides new perspectives to pursue more related biomarkers assess the severity prognosis. Glutathione peroxidase 4 (GPX4) is mainstay regulating ferroptosis. The current study investigated predictive value of GPX4 expression level DKD progression. Methods. We measured levels paraffin sections 85 biopsy-proven patients by immunohistochemistry staining. associations between clinicopathological parameters as well renal outcomes were analyzed. Results. mainly expressed tubulointerstitium, especially tubular epithelial cells patients. was significantly lower than healthy controls. Besides, correlated with proteinuria ( r = − 0.42 , p < 0.001 ), urinary albumin-to-creatinine ratio (uACR) r = − 0.40 p < 0.01 serum creatinine (Scr) r = − 0.59 p < 0.001 estimated glomerular filtration rate (eGFR) r = 0.66 p < 0.001 percentage sclerosed glomeruli r = − 0.42 p < 0.001 ) specimens. During follow-up, positively eGFR slope r = 0.48 p < 0.001 GPX4-low showed higher probability developing end-stage (ESKD) compared GPX4-high p < 0.01 ). Moreover, after adjusting for other potential predictors, still independent predictor ESKD (HR 2.15, 95% CI 1.08 4.28, p < 0.05 Conclusions. Kidney tubulointerstitial associated progression DKD.

Language: Английский

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Biomarkers of Oxidative Stress in Diabetes Mellitus with Diabetic Nephropathy Complications

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13541 - 13541

Published: Aug. 31, 2023

The present study aimed to investigate and compare biomarkers of oxidative stress the activity antioxidant enzymes in plasma patients with different stages diabetic nephropathy. For this purpose, we studied (1) levels reactive oxygen species nitrogen as parameters, (2) lipid protein oxidation, (3) enzymes, (4) cytokine production. Patients type 2 diabetes mellitus were divided into three groups according loss renal function: compensated normal function DMT2N0 measured an estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2, a group decompensated complication nephropathy mild-to-moderate DMT2N1 (eGFR < 60 m2: 59-45 m2), moderate-to-severe DMT2N2 > 30 30-44 m2). All results compared healthy volunteers. showed that had significantly higher ROS, production, end products oxidation Furthermore, depleted nitric oxide (NO), impaired NO synthase (NOS) system, reduced enzyme (p 0.05). These findings suggest are unable compensate for stress. decreased radicals advanced complications may be attributed damage availability plasma. highlights compromised status contributing factor mellitus. have implications understanding pathogenesis role chronic inflammation its development. assessment inflammatory aid early detection prediction complications.

Language: Английский

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Catalpol Attenuates Oxidative Stress and Inflammation via Mechanisms Involving Sirtuin-1 Activation and NF-κB Inhibition in Experimentally-Induced Chronic Kidney Disease

Nutrients, Journal Year: 2023, Volume and Issue: 15(1), P. 237 - 237

Published: Jan. 3, 2023

Chronic kidney disease (CKD) is a stealthy disease, and its development linked to mechanisms including inflammation oxidative stress. Catalpol (CAT), an iridoid glucoside from the root of Rehmannia glutinosa, reported manifest anti-inflammatory, antioxidant, antiapoptotic antifibrotic properties. Hence, we studied possible nephroprotective effects CAT in adenine-induced (0.2% w/w feed for 4 weeks) murine model CKD by administering 5 mg/kg BALB/c mice duration weeks except during weekends. Upon sacrifice, kidney, plasma urine were collected various physiological, biochemical histological endpoints assessed. significantly ameliorated altered body weight, water intake, volume, concentrations urea creatinine plasma, as well clearance albumin ratio. Moreover, effect injury reducing molecule-1, neutrophil gelatinase-associated lipocalin, cystatin C adiponectin. Similarly, augmented markers stress adenine-treated group markedly reduced with pretreatment. Furthermore, prevented deoxyribonucleic acid damage apoptotic activity kidneys. Histologically, formation tubular necrosis dilation, interstitial fibrosis kidney. In addition that, decreased increase phosphorylated NF-κB reversed expression sirtuin-1 conclusion, exhibits salutary against mitigating inflammation, via involving activation inhibition. Confirmatory studies are warranted order consider potent agent CKD.

Language: Английский

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Protective effect of quercetin on cadmium-induced renal apoptosis through cyt-c/caspase-9/caspase-3 signaling pathway

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 16, 2022

Cadmium (Cd), a heavy metal, has harmful effects on animal and human health, it can also obviously induce cell apoptosis. Quercetin (Que) is flavonoid compound with antioxidant other biological activities. To investigate the protective effect of Que Cd-induced renal apoptosis in rats. 24 male SD rats were randomly divided into four groups. They treated as follows: control group was administered orally normal saline (10 ml/kg); Cd injected 2 mg/kg CdCl2 intraperitoneally; + intragastric administration (100 mg/kg); mg/kg). The experimental results showed that body weight Cd-exposed significantly decreased kidney coefficient increased. In addition, increased contents Blood Urea Nitrogen, Creatinine Uric acid. glutathione malondialdehyde tissues. pathological section cause damages such narrow lumen interstitial congestion. kidney, which could activate mRNA protein expression levels Cyt-c, Caspase-9 Caspase-3 Conversely, reduces damage caused by Cd. Kidney alleviated Que. inhibited proteins levels. sum up, injury cells, while reduce reducing oxidative stress inhibiting These provide theoretical basis for clinical application prevention treatment cadmium poisoning.

Language: Английский

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Renoprotective effect of a novel combination of 6-gingerol and metformin in high-fat diet/streptozotocin-induced diabetic nephropathy in rats via targeting miRNA-146a, miRNA-223, TLR4/TRAF6/NLRP3 inflammasome pathway and HIF-1α

Biological Research, Journal Year: 2024, Volume and Issue: 57(1)

Published: July 20, 2024

MiRNA-146a and miRNA-223 are key epigenetic regulators of toll-like receptor 4 (TLR4)/tumor necrosis factor-receptor-associated factor 6 (TRAF6)/NOD-like family pyrin domain-containing 3 (NLRP3) inflammasome pathway, which is involved in diabetic nephropathy (DN) pathogenesis. The currently available oral anti-diabetic treatments have been insufficient to halt DN development progression. Therefore, this work aimed assess the renoprotective effect natural compound 6-gingerol (GR) either alone or combination with metformin (MET) high-fat diet/streptozotocin-induced rats. proposed molecular mechanisms were also investigated.

Language: Английский

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Increased Expression of Circulating Stress Markers, Inflammatory Cytokines and Decreased Antioxidant Level in Diabetic Nephropathy

Medicina, Journal Year: 2022, Volume and Issue: 58(11), P. 1604 - 1604

Published: Nov. 7, 2022

Background and Objectives: The main objective of the present study was to determine role oxidative markers (glutathione (GSH), advanced oxidation protein products (AOPP), glycation end (AGEs), malondialdehyde (MDA)) inflammatory biomarkers (interleukin-6 IL-6, tumor necrosis factor α (TNF-α), myeloperoxide (MPO)) in development diabetic nephropathy along with routinely used biochemical parameters. Materials Method: This a case control study. All selected patients were screened enrolled by convenient non-probability sampling technique at Jinnah hospital Lahore. Informed consent obtained before enrollment subjects. A total 450 study, they divided into three groups, 150 subjects type 2 diabetes diagnosed (DN) vs. healthy individuals as group. Five mL venous blood sample taken from antecubital vein each participant. Statistical analysis performed SPSS. results all variables evaluated using one way ANOVA. Results: mean value parameters (WBCs, platelets, prothrombin time, HbA1c, glucose, urinary albumin-to creatinine ratio (UACR), triglycerides, LDL, HDL, serum creatinine, albumin (creatinine)) increased Hb (g/dL), red cells (RBCs), hematocrit (Hct), free insulin levels, estimated glomerular filtration rate (eGFR) decreased group compared groups. values MDA, AGE, AOPPs significantly GSH level diabetics DN In addition, TNFα, MPO levels also controls. Conclusions: ROS mediated injuries can be prevented restoration an antioxidant defense system, through administration agents. Moreover, mediators are responsible for enhancing inflammation nephropathy.

Language: Английский

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