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https://www.readbyqxmd.com/read/29449563/cinacalcet-mediated-activation-of-the-camkk%C3%AE-lkb1-ampk-pathway-attenuates-diabetic-nephropathy-in-db-db-mice-by-modulation-of-apoptosis-and-autophagy
#1
Ji Hee Lim, Hyung Wook Kim, Min Young Kim, Tae Woo Kim, Eun Nim Kim, Yaeni Kim, Sungjin Chung, Young Soo Kim, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Hye Won Kim, Cheol Whee Park
Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca 2+ concentration and the phosphorylation of Ca 2+ /calmodulin-dependent protein kinase kinaseβ (CaMKKβ)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449307/rage-deletion-confers-renoprotection-by-reducing-responsiveness-to-transforming-growth-factor-%C3%AE-and-increasing-resistance-to-apoptosis
#2
Shinji Hagiwara, Karly Sourris, Mark Ziemann, Wu Tieqiao, Muthukumar Mohan, Aaron D McClelland, Eoin Brennan, Josephine Forbes, Melinda Coughlan, Brooke Harcourt, Sally Penfold, Bo Wang, Gavin Higgins, Raelene Pickering, Assam El-Osta, Merlin C Thomas, Mark E Cooper, Phillip Kantharidis
Signalling via the receptor of advanced glycation end-products (RAGE) although complex and not fully elucidated in the setting of diabetes, is considered a key injurious pathway in the development of diabetic nephropathy (DN). We report here that RAGE deletion resulted in increased expression of fibrotic (collagen I and IV, fibronectin) and the inflammatory marker, MCP-1 in primary mouse mesangial cells (MC) and in kidney cortex. RNA-seq analysis in MCs from RAGE -/- and wild type mice confirmed these observations...
February 15, 2018: Diabetes
https://www.readbyqxmd.com/read/29444469/mangiferin-prevents-diabetic-nephropathy-progression-and-protects-podocyte-function-via-autophagy-in-diabetic-rat-glomeruli
#3
Xiaodan Wang, Lihui Gao, Hua Lin, Jingling Song, Jinwen Wang, Yumin Yin, Jianghu Zhao, Xiangwei Xu, Zhenkun Li, Ling Li
Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes mellitus and is a leading cause of end stage renal disease. Numerous studies suggest that podocyte injury contributes to progressive proteinuria. Podocytes are highly specialized, terminally differentiated cells that are unable to proliferate, autophagy plays a key role in maintaining the structure and function of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte loss, which leads to massive proteinuria in DN...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29442546/vegf-therapy-for-the-kidney-emerging-strategies
#4
Erika Guise, Alejandro R Chade
Renovascular disease (RVD) is prevalent in the elderly, significantly increases cardiovascular risk, and can progressively deteriorate renal function. The loss of renal function in patients with RVD is associated with a progressive dysfunction, damage, and loss of renal microvessels, which pairs with decreased renal bioavailability of vascular endothelial growth factor (VEGF) and a defective vascular repair and proliferation. This association has been the impetus for recent efforts that focused on developing methods to stop the progression of renal injury by protecting the renal microvasculature...
February 14, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29432674/shen-kang-protects-against-tacrolimus-induced-renal-injury
#5
Long Ye Zhang, Jian Jin, Kang Luo, Shang Guo Piao, Hai Lan Zheng, Ji Zhe Jin, Sun Woo Lim, Bum Soon Choi, Chul Woo Yang, Can Li
Background/Aims: Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy. Methods: Rats were treated daily with TAC (1.5mg/kg, subcutaneously) and SK (450 mg/kg, intravenously) for 4 weeks. The effects of SK on TAC-induced renal injury were assessed by measuring renal function, urine albumin excretion, histopathology, inflammatory cell infiltration, expression of profibrotic (transforming growth factor β1 [TGF-β1] and TGF-β inducible gene-h3 [βig-h3]) and proinflammatory cytokines, oxidative stress, and apoptotic cell death...
February 12, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29422999/potassium-bromate-induced-kidney-damage-in-rats-and-the-effect-of-gum-acacia-thereon
#6
Badreldin H Ali, Mohammed Al Za'abi, Turan Karaca, Yousuf Al Suleimani, Khalid A Al Balushi, Priyadarsini Manoj, Mohammed Ashique, Abderrahim Nemmar
Potassium bromate (KBrO3) is used in many countries in cosmetic and food industries. In this work, we investigated in male Sprague-Dawley rats, the effect of four graded oral doses of KBrO3 (5, 15, 45 and 135 mg/kg/day for 28 days) on renal function tests, inflammation, oxidative damage, and apoptosis, as well as on histopathology, using several traditional and novel renal injury biomarkers in plasma, urine and renal tissues. We also tested the possible ameliorative action of the renoprotective prebiotic agent gum acacia (GA) on the actions of KBrO3 when given concomitantly with it in the drinking water at a concentration of 15%w/v...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29421595/improvement-of-cisplatin-induced-renal-dysfunction-by-schisandra-chinensis-stems-via-anti-inflammation-and-anti-apoptosis-effects
#7
Yan-Zi Li, Shen Ren, Xiao-Tong Yan, Yin-Shi Sun, Hui-Ping Li, Wei Li, Ying-Ying Liu, Zi Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill (S. chinensis) is a frequently used traditional Chinese medicine, and modern pharmacological research has proven that S. chinensis has antioxidant, anti-hepatotox, anti-inflammatory, and anti-nephrotoxic effects. Cisplatin is widely used as antineoplastic drug at presenteffects, but the clinical application of cisplatin is limitedowing to nephrotoxicity. AIM OF THE STUDY: To demonstrate the renoprotective activity of the extract of the stems of Schisandra chinensis (SCE) in model mice established by cisplatin triggering acute kidney injury (AKI)...
February 5, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29416624/1-25-dihydroxyvitamin-d3-inhibits-the-proliferation-of-rat-mesangial-cells-induced-by-high-glucose-via-ddit4
#8
Da-Peng Chen, Ye-Ping Ma, Li Zhuo, Zheng Zhang, Gu-Ming Zou, Yue Yang, Hong-Mei Gao, Wen-Ge Li
1,25-Dihydroxyvitamin D3(1,25(OH)2 D3) is a secosteroid with antiproliferative property. It also plays a pivotal renoprotective role in diabetic nephropathy. We investigated whether 1,25(OH)2D3 could inhibit the proliferation of rat mesangial cells exposed to high glucose via the DNA-damage-inducible transcript 4/mammalian target of rapamycin(DDIT4/mTOR) pathway. The cell proliferation rate and cell cycle duration were measured using cell counting kit-8 assay and flow cytometry. Protein expression was assayed by Western blot...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29412120/sodium-glucose-cotransporter-2-inhibitors-and-the-risk-of-diabetic-ketoacidosis-from-pathophysiology-to-clinical-practice
#9
Dimitrios Patoulias, Alexandros Manafis, Christos Mitas, Konstantinos Avranas, Georgios Lales, Ioanna Zografou, Christos Sambanis, Asterios Karagiannis
BACKGROUND: SGLT-2 inhibitors are a novel class of antidiabetic drugs, recently approved for the treatment of patients with T2DM. Their cardioprotective and renoprotective action, along with their beneficial effects on metabolic parameters, make them an attractive therapeutic option. Since 2015, when the US FDA issued warning regarding the increased risk of euDKA in the setting of SGLT-2 inhibitors administration, a vivid discussion upon the direct connection between this novel class and the major metabolic complication of diabetes mellitus is still ongoing...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29399365/urinary-hepcidin-25-is-elevated-in-patients-that-avoid-acute-kidney-injury-following-cardiac-surgery
#10
Nora Choi, Claudio Rigatto, Michael Zappitelli, Ang Gao, Simon Christie, Brett Hiebert, Rakesh C Arora, Julie Ho
Background: Acute kidney injury (AKI) following cardiac surgery leads to increased morbidity and mortality. Characterization and validation of early biomarkers of AKI may ultimately facilitate early therapeutic intervention. We have previously identified that elevated urinary hepcidin-25 is inversely and independently associated with the development of AKI in adult cardiac surgery patients. Hepcidin-25 is an antimicrobial peptide that sequesters iron intracellularly, and its elevation following human ischemia reperfusion injury may represent a renoprotective response to minimize renal injury...
2018: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/29397387/losartan-improves-renal-function-and-pathology-in-obese-zsf-1-rats
#11
Zhi Su, Deborah Widomski, Arthur Nikkel, Laura Leys, Marian Namovic, Diana Donnelly-Roberts, Murali Gopalakrishnan, Steve McGaraughty
BACKGROUND: Losartan, a blocker of the angiotensin II type I receptor, is an important part of the standard of care for diabetic nephropathy (DN). The obese ZSF-1 rats display many aspects of the clinical features of human Type II DN. The current study was designed to examine the treatment effects of losartan on obese ZSF-1 rats and to evaluate the impact of the onset of dosing on efficacy. MATERIALS AND METHODS: The rats (7-10 weeks) underwent a right uninephrectomy (Unx) or sham surgery...
February 5, 2018: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29393366/d%C3%A2-pinitol-alleviates-cyclosporine-a%C3%A2-induced-renal-tubulointerstitial-fibrosis-via-activating-sirt1-and-nrf2-antioxidant-pathways
#12
Eun Sil Koh, Soojeong Kim, Minyoung Kim, Yu Ah Hong, Seok Joon Shin, Cheol Whee Park, Yoon Sik Chang, Sungjin Chung, Ho-Shik Kim
Although the mechanism of cyclosporine A (CsA)‑induced renal injury remains to be fully elucidated, accumulating evidence suggests that oxidative stress is critical in producing CsA‑induced structural and functional renal impairment. The present study investigated the effect of D‑pinitol, a cyclitol present in soybean, on chronic CsA nephropathy. Male ICR mice were treated with vehicle, CsA (30 mg/kg/day), D‑pinitol (50 mg/kg/day) or a combination of CsA and D‑pinitol for 28 days. To assess which pathway responding to oxidative stress is augmented by D‑pinitol, the expression levels of several antioxidant enzymes and their possible regulators were measured...
January 19, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29393124/treatment-of-hyperuricemia-in-chronic-kidney-disease
#13
Juan C Ramirez-Sandoval, Magdalena Madero
Hyperuricemia may be a major contributor to the development or progression of chronic kidney disease (CKD). Although there is no clear cutoff uric acid (UA) value associated to the risk for kidney damage, it appears to be an increased risk as UA rises. Lifestyle interventions such as exercise, weight reduction, low consumption of purine-rich meat, or avoiding high fructose intake are recommended for all hyperuricemic patients. Lowering urate drugs such as allopurinol or febuxostat may be an option as a renoprotective agent; yet, randomized clinical trials evaluating the safety and efficacy of these drugs are limited to a small number of single-center studies...
2018: Contributions to Nephrology
https://www.readbyqxmd.com/read/29391516/the-characterization-renoprotection-and-antioxidation-of-enzymatic-and-acidic-exopolysaccharides-from-hypsizigus-marmoreus
#14
Min Liu, Yufei Lan, Chengye Tian, Yongfa Zhu, Hui Liu, Wenshuai Wang, Weiru Liu, Jianjun Zhang, Le Jia
The present work was designed to investigate the characterization, as well as the antioxidation and renoprotection in streptozocin (STZ)-induced diabetic mice, of exopolysaccharides (EPS) and the enzymatic-EPS (EEPS) and acidic-EPS (AEPS) hydrolysates, which were separated from the fermentation liquor of Hypsizigus marmoreus. Animal results demonstrated that EPS, EEPS and AEPS had potential antioxidant and renoprotective effects, especially EEPS. Additionally, they were the most effective, reflecting increases in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC), and albumin (ALB) of 168...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29383015/protective-effects-of-hydrogen-sulfide-on-chronic-kidney-disease-by-reducing-oxidative-stress-inflammation-and-apoptosis
#15
Hassan Askari, Behjat Seifi, Mehri Kadkhodaee, Nima Sanadgol, Mohammed Elshiekh, Mina Ranjbaran, Parisa Ahghari
The current study aimed to examine the renoprotective effects of long-term treatment with sodium hydrosulfide (NaHS), a prominent hydrogen sulfide donor, in 5/6 nephrectomy animal model. Twenty-four rats were randomly divided into 3 groups including sham-operated group (Sham), 5/6-nephrectomized group (5/6 Nx), and NaHS-treated group (5/6Nx+NaHS). NaHS (30 micromol/l) was added twice daily into the drinking water and renal failure was induced by 5/6 nephrectomy. Twelve weeks after surgical procedure, blood pressure, creatinine clearance (CCr), urine concentration of neutrophil gelatinase associated lipocalin (NGAL) and tissue concentration of malondialdehyde (MDA), superoxide dismutase (SOD), as well as renal morphological changes, apoptosis (cleaved caspase-3) and inflammation (p-NF-κB) were measured...
2018: EXCLI Journal
https://www.readbyqxmd.com/read/29381664/hormone-therapy-and-urine-protein-excretion-a-multiracial-cohort-study-systematic-review-and-meta-analysis
#16
Andrea G Kattah, Maria L G Suarez, Natasa Milic, Kejal Kantarci, Burcu Zeydan, Thomas Mosley, Stephen T Turner, Erin B Ware, Sharon L R Kardia, Vesna D Garovic
OBJECTIVE: Experimental models suggest estrogen has a renoprotective effect, but human studies show variable results. Our objective was to study the association of hormone therapy (HT) and albuminuria in postmenopausal women and to synthesize the results with outcomes from prior studies. METHODS: We analyzed data from postmenopausal women who participated in the second study visit (2000-2004) of the Genetic Epidemiology Network of Arteriopathy (GENOA) study. The exposure was self-reported HT use and the outcome was albuminuria (urine albumin-to-creatinine ratio >25 mg/g creatinine)...
January 29, 2018: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/29373922/development-and-biological-evaluation-of-vesicles-containing-bile-salt-of-telmisartan-for-the-treatment-of-diabetic-nephropathy
#17
Abdul Ahad, Mohammad Raish, Ajaz Ahmad, Fahad I Al-Jenoobi, Abdullah M Al-Mohizea
The aim of present study was to develop and evaluate vesicles containing bile salt formulation of telmisartan for the treatment of diabetic nephropathy. Different vesicles containing bile salt formulations were developed by varying ratios of soybean phosphatidylcholine and sodium deoxycholate. Prepared formulations were characterized for their size, polydispersity index, zeta potential, morphology and entrapment efficiency. Further, the renoprotective outcome of optimized formulation was studied in streptozotocin-induced diabetic nephropathy rat model...
January 26, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29372470/uric-acid-lowering-and-renoprotective-effects-of-topiroxostat-a-selective-xanthine-oxidoreductase-inhibitor-in-patients-with-diabetic-nephropathy-and-hyperuricemia-a-randomized-double-blind-placebo-controlled-parallel-group-study-upward-study
#18
Takashi Wada, Tatsuo Hosoya, Daisuke Honda, Ryusuke Sakamoto, Kazutaka Narita, Tomomitsu Sasaki, Daisuke Okui, Kenjiro Kimura
BACKGROUND: Hyperuricemia is supposed to be an independent risk factor for kidney dysfunction in diabetic patients. We attempted to examine the uric acid-lowering effect and the renoprotective effect of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia in this pilot study. METHODS: The study design was randomized, double-blind, placebo-controlled, parallel-group study. A total of 65 patients with hyperuricemia and diabetic nephropathy with microalbuminuria were enrolled and assigned to either the topiroxostat group or the placebo group...
January 25, 2018: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29367586/neutrophil-gelatinase-associated-lipocalin-attenuates-ischemia-reperfusion-injury-in-an-in-vitro-model-via-autophagy-activation
#19
Cai Yan, Tang Yuanjie, Xu Zhengqun, Chen Jiayan, Li Kongdan
BACKGROUND The aim of this study was to investigate the protective effects of neutrophil gelatinase-associated lipocalin (NGAL) on hypoxia/reoxygenation (H/R) induced acute kidney injury (AKI) in vitro. MATERIAL AND METHODS We used NRK-52E cells and H/R treatments to mimic ischemia/reperfusion injury (IRI) in vitro. Experimental groups were: the control group, the H/R group, the 3-methyladenine (3-MA)+H/R group, the NGAL (0.25, 0.5, and 1 ug/mL)+H/R group, and the NGAL (0.25, 0.5, 1 ug/mL)+3-MA+H/R group. After 24 hours of culture, cell proliferation was analyzed by CCK-8 assay...
January 25, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29364584/a-review-of-dipeptidyl-peptidase-4-inhibitors-hot-topics-from-randomized-controlled-trials
#20
REVIEW
Carolyn F Deacon
The first clinical study to investigate effects of dipeptidyl peptidase-4 (DPP-4) inhibition was published in 2002, and since then, numerous randomized controlled trials (RCTs) have shown that DPP-4 inhibitors are efficacious, safe and well-tolerated. This review will focus upon RCTs which have investigated DPP-4 inhibitors in patient groups which are often under-represented or excluded from typical phase 3 clinical trials. Large cardiovascular (CV) safety outcome trials in patients with established CV disease have confirmed that DPP-4 inhibitors are not associated with any additional CV risk in these already-at-high-risk individuals, while raising awareness of any uncommon adverse events, such as heart failure hospitalization seen in one of the trials...
February 2018: Diabetes, Obesity & Metabolism
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