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Xin-Long Wang, Feng-Jiao Zhou, Man Dou, Yong-Ming Yan, Shu-Mei Wang, Lei Di, Yong-Xian Cheng
Ganoderma mushrooms are of great nutritious and medicinal values. This study was designed to characterize compounds from the fruiting bodies of Ganoderma cochlear and investigate their protective effects against kidney disorders. Six novel meroterpenoids cochlearoids F-K (1-6) were isolated by utilizing phytochemical approaches. Their structures were identified on the basis of extensive spectroscopic data and calculation methods. Biological evaluation shows that compounds 1-4 and 6 exhibit potent inhibitory activity on fibronectin overproduction in TGF-β1-induced HKC-8 cells...
October 7, 2016: Bioorganic & Medicinal Chemistry Letters
Futoshi Matsui, Stephen Babitz, Audrey Rhee, Karen L Hile, Hongji Zhang, Kirstan Kathleen Meldrum
STAT3 is a transcription factor implicated in renal fibrotic injury, but the role of STAT3 in mesenchymal stem cell (MSC)-induced renoprotection during renal fibrosis remains unknown. We hypothesized that MSCs protect against obstruction-induced renal fibrosis by downregulating STAT3 activation and STAT3-induced matrix metalloproteinase 9 (MMP-9) expression. Male Sprague-Dawley rats underwent renal arterial injection of vehicle or MSCs (1 x 106 per rat) immediately prior to sham operation or induction of unilateral ureteral obstruction (UUO)...
October 19, 2016: American Journal of Physiology. Renal Physiology
P Fabbrini, K Finkel, M Gallieni, G Capasso, M Cavo, A Santoro, S Pasquali
Acute kidney injury (AKI) is a frequent complication of multiple myeloma and is associated with increased short-term mortality. Additionally, even a single episode of AKI can eventually lead to end-stage renal disease (ESRD), significantly reducing quality of life and long-term survival. In the setting of multiple myeloma, severe AKI (requiring dialysis) is typically secondary to cast nephropathy (CN). Renal injury in CN is due to intratubular obstruction from precipitation of monoclonal serum free light chains (sFLC) as well as direct tubular toxicity of sFLC via stimulation of nuclear factor (NF)κB inflammatory pathways...
October 18, 2016: Journal of Nephrology
Shokei Kim-Mitsuyama
There is accumulating evidence that RAS inhibitors not only reduce blood pressure, but also exert pleiotropic effects, including a renoprotective effect, amelioration of insulin resistance, reduction in onset of diabetes, and suppression of cardiovascular remodelling,. However, the definite benefit of RAS inhibition in treatment of hypertension with CKD or DM is not conclusive. We previously performed the OlmeSartan and Calcium Antagonists Randomized (OSCAR) study comparing the preventive effect of high-dose ARB therapy versus ARB plus CCB combination therapy on cardiovascular morbidity and mortality in 1164 Japanese elderly hypertensive patients with baseline type 2 diabetes and/or CVD (Am J Med (2012))...
September 2016: Journal of Hypertension
Peter Mertens
Remarkable progress has been achieved in the field of diabetes with the development of incretin analogues, dipeptidyl peptidase IV inhibitors and novel insulin analogues; nevertheless, there is an unmet need for additional therapeutic options. The new generation of drugs, denoted gliflozines, that specifically interfere with sodium-glucose cotransporters (SGLT)-2 and exhibit a favourable impact on glucose metabolism in patients with type 2 diabetes are emerging as hopeful avenues. The resultant negative energy balance caused by glucosuria results in long-term weight losses, significantly reduced HbA1c levels approximating 0...
September 2016: Journal of Hypertension
Bernt Johan von Scholten, Frederik Persson, Signe Rosenlund, Peter Hovind, Jens Faber, Tine Willum Hansen, Peter Rossing
AIMS: Patients with type 2 diabetes and albuminuria have high cardiorenal morbidity and mortality despite multifactorial treatment. Short-term reduction in albuminuria is considered suggestive of long-term renoprotective effects. We evaluated the renal effects of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on top of multifactorial care, including renin-angiotensin-system (RAS)-inhibition. MATERIALS AND METHODS: Randomised, double-blind, placebo-controlled, cross-over trial including patients with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio > 30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1...
October 17, 2016: Diabetes, Obesity & Metabolism
Vasilios Tsimihodimos, Theodosios D Filippatos, Sebastian Fillippas-Ntekouan, Moses S Elisaf
Sodium-glucose co-transporter 2 inhibitors (SGLT-2) inhibitors) represent a new class of antidiabetic drugs that act through the inhibition of glucose and sodium reabsorption at proximal tubules. It has been shown that tThese substances may exhibit renonephroprotective properties, since they expressed clinically as a prevention of the deterioration of the glomerular filtration rate and a reductionreduce in the degree of albuminuria in patients with established diabetes-associated kidney disease. In this review we present in detail the pathophysiologic mechanisms that have been recently implicated in the rennephroprotective properties of SGLT-2 inhibitors...
October 7, 2016: Current Vascular Pharmacology
Chengyuan Tang, Juan Cai, Zheng Dong
Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, but the underlying mechanism is poorly understood. Szeto et al. now unravel a central role of mitochondrial dysfunction in a high fat diet-induced glomerulopathy and proximal tubular injury. Moreover, they demonstrate the renoprotective effect of SS31, a mitochondria-targeted antioxidant, in related models. Targeting mitochondria may offer a novel strategy for the therapy of obesity-related kidney disease...
November 2016: Kidney International
Masatoshi Kubota, Reiko Watanabe, Miki Yamaguchi, Michihiro Hosojima, Akihiko Saito, Mikio Fujii, Shinobu Fujimura, Motoni Kadowaki
We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period...
October 2016: British Journal of Nutrition
Jianxiao Shen, Ling Wang, Na Jiang, Shan Mou, Minfang Zhang, Leyi Gu, Xinghua Shao, Qin Wang, Chaojun Qi, Shu Li, Wanpeng Wang, Xiajing Che, Zhaohui Ni
Iodinated contrast media serves as a direct causative factor of acute kidney injury (AKI) and is involved in the progression of cellular dysfunction and apoptosis. Emerging evidence indicates that NLRP3 inflammasome triggers inflammation, apoptosis and tissue injury during AKI. Nevertheless, the underlying renoprotection mechanism of NLRP3 inflammasome against contrast-induced AKI (CI-AKI) was still uncertain. This study investigated the role of NLRP3 inflammasome in CI-AKI both in vitro and in vivo. In HK-2 cells and unilateral nephrectomy model, NLRP3 and NLRP3 inflammasome member ASC were significantly augmented with the treatment of contrast media...
October 10, 2016: Scientific Reports
Xiu Hong Yang, Yu Pan, Xiao Li Zhan, Bao Long Zhang, Li Li Guo, Hui Min Jin
Epigallocatechin-3-gallate (EGCG), extracted from green tea, has been shown to have antioxidative activity. In the present study, we evaluated the effect of EGCG on the kidney function in db/db mice and also tried to investigate the underlying mechanism of the renoprotective effects of EGCG in both animals and cells. EGCG treatment could decrease the level of urinary protein, 8-iso-PGF2a, and Ang II. Moreover, EGCG could also change the level of several parameters associated with oxidative stress. In addition, the protein expression levels of AT-1R, p22-phox, p47-phox, p-ERK1/2, p-p38 MAPK, TGF-β1, and α-SMA in diabetic db/db mice were upregulated, and all of these symptoms were downregulated with the treatment of EGCG at 50 and 100 mg/kg/d...
2016: Oxidative Medicine and Cellular Longevity
J Tamargo, Luis Miguel Ruilope
Voltage-gated Ca(2+) channels are the primary route of Ca(2+) entry in vascular smooth muscle cells, playing a key role in the regulation of arterial tone and blood pressure. Since the 60´s, L-type Ca(2+) channel blockers (CCBs) have been widely used for the treatment of hypertension. Areas covered. T-type Ca(2+) channels regulate vascular tone in small-resistance vessels and aldosterone secretion, and N-type channels expressed in sympathetic nerve terminals regulate the release of neurotransmitters. We performed a literature search in MEDLINE, PubMed and ClinicalTrials...
October 4, 2016: Expert Opinion on Investigational Drugs
Steven T Haller, Sivarajan Kumarasamy, David A Folt, Leah M Wuescher, Stanislaw Stepkowski, Manish Karamchandani, Harshal Waghulde, Blair Mell, Muhammad Chaudhry, Kyle Maxwell, Siddhi Upadhyaya, Christopher A Drummond, Jiang Tian, Wanda E Filipiak, Thomas L Saunders, Joseph I Shapiro, Bina Joe, Christopher J Cooper
High blood pressure is a common cause of chronic kidney disease. Because CD40, a member of the tumor necrosis factor receptor family, has been linked to the progression of kidney disease in ischemic nephropathy, we studied the role of Cd40 in the development of hypertensive renal disease. The Cd40 gene was mutated in the Dahl S genetically hypertensive rat with renal disease by targeted-gene disruption using zinc-finger nuclease technology. These rats were then given low (0.3%) and high (2%) salt diets and compared...
September 28, 2016: Kidney International
Qin Zhang, Lin Liu, Wenjun Lin, Shasha Yin, Aiping Duan, Zhihong Liu, Wangsen Cao
Rhein is an anthraquinone compound isolated from the medicinal plant rhubarb and mainly used in the clinical treatment of diabetic nephropathy. Rhein exhibits various renoprotective functions, but the underlying mechanisms are not fully determined. However, its renoprotective properties recapitulate the role of Klotho, a renal-specific antiaging protein critical for maintaining kidney homeostasis. Here we explored the connections between rhein renoprotection and Klotho in a mouse model of adenine-induced chronic kidney disease...
September 27, 2016: Kidney International
Juan Zhan, Kun Wang, Conghui Zhang, Chunxiu Zhang, Yueqiang Li, Ying Zhang, Xiaoyan Chang, Qiaodan Zhou, Ying Yao, Yanyan Liu, Gang Xu
Grape seed proanthocyanindin extract (GSPE) is a polyphenolic bioflavonoid derived from grape seeds and has been widely studied for its potent antioxidant, anti-inflammatory and antitumor activities. HMGB1 is a newly discovered danger-associated molecular pattern (DAMP) that has potent proinflammatory effects once released by necrotic cells. However, the effect of GSPE on the HMGB1, and the relationship of those two with acute kidney injury and chronic kidney fibrosis are unknown. This study aimed to investigate the impact of GSPE on acute kidney injury and chronic fibrosis...
2016: International Journal of Molecular Sciences
Elham Peysepar, Nepton Soltani, Mehdi Nematbakhsh, Fatemeh Eshraghi-Jazi, Ardeshir Talebi
INTRODUCTION: Cisplatin (CP) is a major antineoplastic drug for treatment of solid tumors. CP-induced nephrotoxicity may be gender-related. This is while gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the central nervous system that has renoprotective impacts on acute renal injury. OBJECTIVES: This study was designed to investigate the protective role of GABA against CP-induced nephrotoxicity in male and female rats. MATERIALS AND METHODS: Sixty Wistar male and female rats were used in eight experimental groups...
2016: Journal of Renal Injury Prevention
Valeria Cernaro, Alessandra Sfacteria, Claudia Rifici, Francesco Macrì, Giulia Maricchiolo, Antonio Lacquaniti, Carlo Alberto Ricciardi, Antoine Buemi, Giuseppe Costantino, Domenico Santoro, Michele Buemi
BACKGROUND: Gentamicin is an aminoglycoside antibiotic widely used in the treatment of infections caused by Gram-negative bacteria. The main limitation to its therapeutic effectiveness is the potential nephrotoxicity. Erythropoietin has a tissue protective effect widely demonstrated in the kidney. The aim of the present study was to evaluate the renoprotective effects of erythropoietin in a model of zebrafish (Danio rerio) after administration of gentamicin. METHODS: Sixty adult zebrafish were subdivided into three groups: group A was treated with gentamicin; group B received gentamicin and, 24 h later, epoetin alpha; group C received drug diluent only...
September 27, 2016: Journal of Nephrology
Mushtaq Ahmad Ansari, Mohammad Raish, Ajaz Ahmad, Sheikh Fayaz Ahmad, Shahid Mudassar, Kazi Mohsin, Faiyaz Shakeel, Hesham M Korashy, Saleh A Bakheet
AIMS: In this study, the renoprotective functions of sinapic acid (SA), a polyphenol, on gentamicin-induced nephrotoxicity and the pathway that mediates this function were examined. MAIN METHODS: Kidney function markers (serum urea, uric acid, creatinine, LDH, and γ-GGT) and histopathological examinations of the kidney were used to evaluate gentamicin-induced nephrotoxicity. Oxidative stress markers (lipid peroxidation and total protein), renal nitrosative stress (nitric oxide), antioxidant enzymes (catalase and NP-SH), inflammation markers (NF-κB [p65], TNF-α, IL-6, and myeloperoxidase [MPO]), and apoptotic markers (caspase 3, Bax, and Bcl-2) were also assessed...
September 21, 2016: Life Sciences
Shao-Yu Yang, Shuei-Liong Lin, Yung-Ming Chen, Vin-Cent Wu, Wei-Shiung Yang, Kwan-Dun Wu
Activation of sirtuin 1 (Sirt1) attenuates unilateral ureteral obstruction (UUO)-induced inflammation and fibrosis, suggesting that Sirt1 may prevent tubulointerstitial fibrosis. In this study, we explored changes in the expression of Sirt1 in the kidneys of UUO-treated rats and evaluated the effects of Sirt1 activation or inhibition on renal pathology and mediators of UUO pathogenesis, especially angiotensin II and nuclear factor (NF)-κB, in rats and rat renal fibroblasts. Sirt1 expression increased in the obstructed kidney but not in the contralateral kidney and was mainly detected in tubulointerstitial cells...
2016: Scientific Reports
Thiago Bruder-Nascimento, Glaucia Callera, Augusto Cesar Montezano, Tayze T Antunes, Ying He, Aurelie Nguyen Dinh Cat, Nathanne S Ferreira, Pedro A Barreto, Vânia C Olivon, Rita C Tostes, Rhian M Touyz
Potential benefits of statins in the treatment of chronic kidney disease beyond lipid-lowering effects have been described. However, molecular mechanisms involved in renoprotective actions of statins have not been fully elucidated. We questioned whether statins influence development of diabetic nephropathy through reactive oxygen species, RhoA and Akt/GSK3 pathway, known to be important in renal pathology. Diabetic mice (db/db) and their control counterparts (db/+) were treated with atorvastatin (10 mg/Kg/day, p...
2016: PloS One
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