Diabetic fibrosis

Tuleta, Izabela; Frangogiannis, Nikolaos G.

doi:10.1016/j.bbadis.2020.166044

Cited by 124 publications

(75 citation statements)

References 316 publications

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“…We found that PTUPB effectively decreased tubular injury both in the renal cortex and medulla. A common manifestation of various kinds of kidney injury is fibrosis, and VEGF inhibition has been found to exacerbate fibrosis in other organ systems such as the lungs ( Partovian et al, 2000 ; Tuleta and Frangogiannis, 2021 ). We found that PTUPB halted the progression of renal fibrosis caused by sorafenib.…”

Section: Discussionmentioning

confidence: 99%

Dual sEH/COX-2 Inhibition Using PTUPB—A Promising Approach to Antiangiogenesis-Induced Nephrotoxicity

et al. 2021

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Kidney injury from antiangiogenic chemotherapy is a significant clinical challenge, and we currently lack the ability to effectively treat it with pharmacological agents. Thus, we set out to investigate whether simultaneous soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) inhibition using a dual sEH/COX-2 inhibitor PTUPB could be an effective strategy for treating antiangiogenic therapy-induced kidney damage. We used a multikinase inhibitor, sorafenib, which is known to cause serious renal side effects. The drug was administered to male Sprague–Dawley rats that were on a high-salt diet. Sorafenib was administered over the course of 56 days. The study included three experimental groups; 1) control group (naïve rats), 2) sorafenib group [rats treated with sorafenib only (20 mg/kg/day p.o.)], and 3) sorafenib + PTUPB group (rats treated with sorafenib only for the initial 28 days and subsequently coadministered PTUPB (10 mg/kg/day i.p.) from days 28 through 56). Blood pressure was measured every 2 weeks. After 28 days, sorafenib-treated rats developed hypertension (161 ± 4 mmHg). Over the remainder of the study, sorafenib treatment resulted in a further elevation in blood pressure through day 56 (200 ± 7 mmHg). PTUPB treatment attenuated the sorafenib-induced blood pressure elevation and by day 56, blood pressure was 159 ± 4 mmHg. Urine was collected every 2 weeks for biochemical analysis. After 28 days, sorafenib rats developed pronounced proteinuria (9.7 ± 0.2 P/C), which intensified significantly (35.8 ± 3.5 P/C) by the end of day 56 compared with control (2.6 ± 0.4 P/C). PTUPB mitigated sorafenib-induced proteinuria, and by day 56, it reduced proteinuria by 73%. Plasma and kidney tissues were collected on day 56. Kidney histopathology revealed intratubular cast formation, interstitial fibrosis, glomerular injury, and glomerular nephrin loss at day 56 in sorafenib-treated rats. PTUPB treatment reduced histological features by 30%–70% compared with the sorafenib-treated group and restored glomerular nephrin levels. Furthermore, PTUPB also acted on the glomerular permeability barrier by decreasing angiotensin-II-induced glomerular permeability to albumin. Finally, PTUPB improved in vitro the viability of human mesangial cells. Collectively, our data demonstrate the potential of using PTUPB or dual sEH/COX-2 inhibition as a therapeutic strategy against sorafenib-induced glomerular nephrotoxicity.

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Section: Discussionmentioning

confidence: 99%

Dual sEH/COX-2 Inhibition Using PTUPB—A Promising Approach to Antiangiogenesis-Induced Nephrotoxicity

et al. 2021

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“…Эксперты Европейского консенсуса выделяют 4 класса ПКМП в зависимости от гистологических изменений предсердий и этиологического фактора. У больных с изолированной формой фибрилляции предсердий (ФП), сахарным диабетом (СД), генетически обусловленными аномалиями, преимущественно связанными с образованием и выделением предсердных натрийуретических пептидов (НУП), выделяют ПКМП первого класса [5,6]. Согласно Рекомендациям Европейского общества кардиологов (2020), термин "изолированная ФП" не включен в современную классификацию и не рекомендуется использовать в клинической практике [7].…”

Section: Discussionunclassified

Novel diagnostic criteria for atrial cardiomyopathy in patients with type 2 diabetes and atrial fibrillation

2021

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Aim. To determine additional diagnostic criteria for atrial cardiomyopathy in patients with type 2 diabetes (T2D) and paroxysmal/persistent atrial fibrillation (AF).Material and methods. This cross-sectional screening clinical study included 80 patients with AF and T2D, who were divided into 2 groups depending on the left (LAVI) or right atrial volume index (RAVI) according to echocardiography: the first group included 49 patients with increased LAVI, while the second — 31 patients without changes in LAVI and RAVI. Inclusion criteria were presence of paroxysmal or persistent AF, T2D, age up to 65 years. There were following exclusion criteria: current smoking and less than 1 year old, the presence of cardiovascular and pulmonary diseases, heart failure, implanted artificial pacemaker, prior radiofrequency ablation; valvular heart disease and prosthetics; acute myocarditis, infective endocarditis, hypertrophic, dilated, and restrictive cardiomyopathies, storage diseases, severe liver diseases; thyroid disorders; cancer; acute inflammatory and infectious diseases; alcohol abuse, dementia and mental illness.Results. The groups did not differ significantly in terms of sex, age, cardiovascular risk factors, risk of stroke and bleeding when using anticoagulants, clinical and laboratory parameters, and the structure of drug therapy. The following parameters significant differ between the groups: LAVI (according to study design), mid-regional pro-atrial natriuretic peptide (MR-proANP), glomerular filtration rate (GFR) calculated by creatinine, tissue inhibitor of matrix metalloproteinases 1 (TIMP-1). For MR-proANP, GFR, TIMP-1, ROC curves were created in order to determine its clinical significance and operational characteristics of parameters. GFR, as a diagnostic criterion, showed unsatisfactory clinical significance when constructing the ROC curve: AUC (area under the curve) was 0,38. The MR-proANP of 62,3-85 pmol/L and TIMP-1 of 156 ng/ml and higher allows verification of atrial cardiomyopathy in patients with T2D and AF at AUC of 0,83 (95% confidence interval (CI), 0,73; 0,92) and 0,90 (95% CI, 0,83; 0,98), respectively.Conclusion. The blood MR-proANP concentration of 62,3-85 pmol/L is diagnostic for atrial cardiomyopathy in patients with T2D and AF with the sensitivity and specificity of 96,8% and 75,5%, respectively, while TIMP-1 values of 156 ng/ml and above had the sensitivity and specificity of 90,3% and 87,8%, respectively.

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“…TGF-β1 is a major cytokine secreted by mesangial cells that mediates the development of DN [33] . TGF-β1 is a key cytokine mediating collagen deposition in kidney, including promoting the production of ECM, inhibiting the degradation of ECM and participating in renal brosis [34,35] . ECM of DN patients is produced by mesangial cells and mainly consists of bronectin, type IV collagen and a small amount of type I collagen.…”

Section: Discussionmentioning

confidence: 99%

Oridonin Attenuates Diabetes‑Induced Renal Fibrosis via Inhibition of the TXNIP/NLRP3 and NF‑κB Pathway in Rats

Huang

Zhang

et al. 2021

Preprint

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Background: Oxidative stress and its induced inflammation are important pathological processes of diabetic nephropathy (DN). Oridonin, a component isolated from Rabdosia rubescens, possesses remarkable anti-inflammatory, immunoregulatory properties, it is also a newly reported NLRP3 inhibitor. However, the renoprotective effects of Oridonin and the underlying molecular mechanisms have not been explored in DN. We hypothesized that Oridonin could reduce NLRP3 pathway and ameliorate diabetes‑induced renal fibrosis.Methods: We used STZ-induced diabetic rats combined high-fat diet to establish a T2DM animal model, and then treated with Oridonin (10, 20 mg/kg/day) for two weeks. Kidney function and renal fibrosis were assessed. In addition, the expression of inflammatory factors and fibrotic markers were analyzed by western blot.Results: Oridonin treatment preserved kidney function and markedly limited the renal fibrosis size in diabetic rats. The renal fibrotic markers were inhibited in the 10 mg/kg/day group and 20 mg/kg/day group compared to the T2DM group. Moreover, the expression levels of TXNIP/NLRP3 and NF‑κB pathway were decreased in the Oridonin treatment group compared to non-treated group. Conclusions: The NLRP3-inflammasome inhibitor Oridonin reduces renal fibrosis and preserves kidney function in T2DM rat model, which indicates potential therapeutic effect of Oridonin on DN.

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Diabetic fibrosis

Cited by 124 publications

References 316 publications

Dual sEH/COX-2 Inhibition Using PTUPB—A Promising Approach to Antiangiogenesis-Induced Nephrotoxicity

Dual sEH/COX-2 Inhibition Using PTUPB—A Promising Approach to Antiangiogenesis-Induced Nephrotoxicity

Novel diagnostic criteria for atrial cardiomyopathy in patients with type 2 diabetes and atrial fibrillation

Oridonin Attenuates Diabetes‑Induced Renal Fibrosis via Inhibition of the TXNIP/NLRP3 and NF‑κB Pathway in Rats

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