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Fenofibrate AND nephropathy

Laura Castiglioni, Alice Pignieri, Melania Fiaschè, Marco Giudici, Maurizio Crestani, Nico Mitro, Mauro Abbate, Carlamaria Zoja, Daniela Rottoli, Claudia Foray, Fabio Fiordaliso, Uliano Guerrini, Elena Tremoli, Luigi Sironi, Paolo Gelosa
OBJECTIVES: The simultaneous presence of cardiac and renal diseases is a pathological condition that leads to increased morbidity and mortality. Several lines of evidence have suggested that lipid dysmetabolism and mitochondrial dysfunction are pathways involved in the pathological processes affecting the heart and kidney. In the salt-loaded spontaneously hypertensive stroke-prone rat (SHRSP), a model of cardiac hypertrophy and nephropathy that shows mitochondrial alterations in the myocardium, we evaluated the cardiorenal effects of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist that acts by modulating mitochondrial and peroxisomal fatty acid oxidation...
May 2018: Journal of Hypertension
Lili Cheng, Mengmeng Ge, Zhou Lan, Zhilong Ma, Wenna Chi, Wenhua Kuang, Kun Sun, Xinbin Zhao, Ye Liu, Yaqian Feng, Yuedong Huang, Maoguo Luo, Liping Li, Bin Zhang, Xiaoyu Hu, Lina Xu, Xiaohui Liu, Yi Huo, Haiteng Deng, Jinliang Yang, Qiaoran Xi, Yonghui Zhang, Julie A Siegenthaler, Ligong Chen
Zoledronate is a bisphosphonate that is widely used in the treatment of metabolic bone diseases. However, zoledronate induces significant nephrotoxicity associated with acute tubular necrosis and renal fibrosis when administered intravenously. There is speculation that zoledronate-induced nephrotoxicity may result from its pharmacological activity as an inhibitor of the mevalonate pathway but the molecular mechanisms are not fully understood. In this report, human proximal tubular HK-2 cells and mouse models were combined to dissect the molecular pathways underlying nephropathy caused by zoledronate treatments...
January 2018: Archives of Toxicology
Wen-Wen Li, Di Huang, Pei-Cheng Shen, Qing Wu, Chuan Sun, Xian-Xian Wang, Li-Qun He
OBJECTIVES: To determine the underlying mechanism of Gubentongluo Formula in the treatment of IgA nephropathy (IgAN). METHODS: C57BL/6 mice were randomly divided into four groups: normal group (n =10), IgAN group (n =10), control group (n =10) and treatment group (n =10). Mice in the normal and IgAN groups were intragastricly administered with normal saline for 12 weeks; while those in the control and treatment groups were given fenofibrate [30 mg/(kg!$d) and Gubentongluo Formula [1...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
Dongqing Zha, Xiaoyan Wu, Ping Gao
Diabetic kidney disease (DKD) is a major complication for diabetic patients. Adiponectin is an insulin sensitizer and anti-inflammatory adipokine and is mainly secreted by adipocytes. Two types of adiponectin receptors, AdipoR1 and AdipoR2, have been identified. In both type 1 and type 2 diabetes (T2D) patients with DKD, elevated adiponectin serum levels have been observed, and adiponectin serum level is a prognostic factor of end-stage renal disease. Renal insufficiency and tubular injury possibly play a contributory role in increases in serum and urinary adiponectin levels in diabetic nephropathy by either increasing biodegradation or elimination of adiponectin in the kidneys, or enhancing production of adiponectin in adipose tissue...
July 1, 2017: Endocrinology
Niloy Bhattacharjee, Sujata Barma, Nandita Konwar, Saikat Dewanjee, Prasenjit Manna
Diabetic nephropathy (DN), a chronic complication of diabetes, is charecterized by glomerular hypertrophy, proteinuria, decreased glomerular filtration, and renal fibrosis resulting in the loss of renal function. Although the exact cause of DN remains unclear, several mechanisms have been postulated, such as hyperglycemia-induced renal hyper filtration and renal injury, AGEs-induced increased oxidative stress, activated PKC-induced increased production of cytokines, chemokines, and different inflammatory and apoptotic signals...
November 15, 2016: European Journal of Pharmacology
Rui Cheng, Lexi Ding, Xuemin He, Yusuke Takahashi, Jian-Xing Ma
Peroxisome proliferator-activated receptor-α (PPARα) displays renoprotective effects with an unclear mechanism. Aberrant activation of the canonical Wnt pathway plays a key role in renal fibrosis. Renal levels of PPARα were downregulated in both type 1 and type 2 diabetes models. The PPARα agonist fenofibrate and overexpression of PPARα both attenuated the expression of fibrotic factors, and suppressed high glucose-induced or Wnt3a-induced Wnt signaling in renal cells. Fenofibrate inhibited Wnt signaling in the kidney of diabetic rats...
December 2016: Diabetes
Nouf Mohamed Al-Rasheed, Nawal Mohamed Al-Rasheed, Maha Abdelrahman Al-Amin, Iman Huesein Hasan, Hanaa Najeeb Al-Ajmi, Raeesa Ahmed Mohammad, Hala Aboulfotooh Attia
CONTEXT: Fibrates, the ligands of peroxisome profileferator-activated receptor-α have been shown to have a renal protective action in diabetic nephropathy (DN). OBJECTIVE: This study aimed to elucidate the effect of fenofibrate on renal transforming growth factor-β1 (TGF-β1) and Smad3 in Streptozotocin (STZ)-induced DN. METHODS: Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (55 mg/kg). Diabetic rats were given fenofibrate (100 mg/kg, p...
October 2016: Archives of Physiology and Biochemistry
Yanli Cheng, Jingjing Zhang, Weiying Guo, Fengsheng Li, Weixia Sun, Jing Chen, Chi Zhang, Xuemian Lu, Yi Tan, Wenke Feng, Yaowen Fu, Gilbert C Liu, Zhonggao Xu, Lu Cai
The lipid lowering medication, fenofibrate (FF), is a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, possessing beneficial effects for type 2 diabetic nephropathy (DN). We investigated whether FF can prevent the development of type 1 DN, and the underlying mechanisms. Diabetes was induced by a single intraperitoneal injection of streptozotocin in C57BL/6J mice. Mice were treated with oral gavage of FF at 100mg/kg every other day for 3 and 6 months. Diabetes-induced renal oxidative stress, inflammation, apoptosis, lipid and collagen accumulation, and renal dysfunction were accompanied by significant decrease in PI3K, Akt, and GSK-3β phosphorylation as well as an increase in the nuclear accumulation of Fyn [a negative regulator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]...
April 2016: Free Radical Biology & Medicine
Nikolaos Papanas, Dan Ziegler
Distal symmetric sensorimotor polyneuropathy (DSPN) is the most common neurological manifestation in diabetes. Major risk factors of DSPN include diabetes duration, hyperglycemia, and age, followed by prediabetes, hypertension, dyslipidemia, and obesity. Height, smoking, insulin resistance, hypoinsulinemia, and others represent an additional risk. Importantly, hyperglycemia, hypertension, dyslipidemia, obesity, and smoking are modifiable. Stringent glycemic control has been shown to be effective in type 1, but not to the same extent in type 2 diabetes...
April 2015: Review of Diabetic Studies: RDS
Theodosios D Filippatos, Moses S Elisaf
INTRODUCTION: Fenofibrate/simvastatin combination is useful for patients with mixed dyslipidemia. Aim of this review is to critically present the safety aspects of the fenofibrate/simvastatin combination. AREAS COVERED: Current evidence regarding the adverse effects of fenofibrate/simvastatin combination is critically presented based on the results of large randomized controlled trials and other relevant studies. Additionally, clinical pharmacology, drug interactions and the effects of fenofibrate and simvastatin on metabolic variables and cardiovascular risk are briefly described...
2015: Expert Opinion on Drug Safety
Kwok-Leung Ong, Andrzej S Januszewski, Rachel O'Connell, Luke Buizen, Alicia J Jenkins, Aimin Xu, David R Sullivan, Philip J Barter, Russell S Scott, Marja-Riitta Taskinen, Kerry-Anne Rye, Anthony C Keech
AIMS/HYPOTHESIS: Baseline circulating fibroblast growth factor 21 (FGF21) levels can predict total cardiovascular disease events in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. This paper describes the relationship of baseline FGF21 levels and new on-study microvascular disease in patients with type 2 diabetes from the FIELD study. METHODS: Baseline FGF21 levels were measured in plasma by enzyme-linked immunosorbent assay in 9697 study participants...
September 2015: Diabetologia
Nawal M Al-Rasheed, Nouf M Al-Rasheed, Hala A Attia, Maha A Al-Amin, Hanaa N Al-Ajmi, Iman H Hasan, Raeesa A Mohamad, Nasr A Sinjilawi
This study was conducted to investigate whether the renoprotective effects of fenofibrate are mediated via attenuation of endothelial dysfunction and modulating the mRNA expression of adenosine monophosphate-activated protein kinase (AMPK) and its downstream kinase liver kinase B1 (LKB1) in rats with diabetic nephropathy (DN). Diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg kg(-1)). Fenofibrate (100 mg kg(-1), p.o.) was given to diabetic rats daily for 12 weeks. Treatment with fenofibrate significantly improved the renal function as revealed by the significant reductions in urinary albumin excretion and serum levels of creatinine and urea, in addition to the significant increase in creatinine clearance compared with the diabetic control group...
2015: Pharmacology
Krisztian Stadler, Ira J Goldberg, Katalin Susztak
Although diabetes is mainly diagnosed based on elevated glucose levels, dyslipidemia is also observed in these patients. Chronic kidney disease (CKD), a frequent occurrence in patients with diabetes, is associated with major abnormalities in circulating lipoproteins and renal lipid metabolism. At baseline, most renal epithelial cells rely on fatty acids as their energy source. CKD, including that which occurs in diabetes, is characterized by tubule epithelial lipid accumulation. Whether this is due to increased uptake or greater local fatty acid synthesis is unknown...
July 2015: Current Diabetes Reports
Markus Herrmann, David R Sullivan, Anne-Sophie Veillard, Thomas McCorquodale, Isabella R Straub, Russell Scott, Markku Laakso, Duncan Topliss, Alicia J Jenkins, Stefan Blankenberg, Anthony Burton, Anthony C Keech
OBJECTIVE: People with diabetes frequently develop vascular disease. We investigated the relationship between blood 25-hydroxyvitamin D (25OH-D) concentration and vascular disease risk in type 2 diabetes. RESEARCH DESIGN AND METHODS: The relationships between blood 25OH-D concentration at baseline and the incidence of macrovascular (including myocardial infarction and stroke) and microvascular (retinopathy, nephropathy, neuropathy, and amputation) disease were analyzed with Cox proportional hazards models and logistic regression in an observational study of patients in the 5-year Fenofibrate Intervention and Event Lowering in Diabetes trial...
March 2015: Diabetes Care
Pitchai Balakumar, Rajavel Varatharajan, Ying Hui Nyo, Raja Renushia, Devarajan Raaginey, Ann Nah Oh, Shaikh Sohrab Akhtar, Mani Rupeshkumar, Karupiah Sundram, Sokkalingam A Dhanaraj
Low-doses of fenofibrate and dipyridamole have pleiotropic renoprotective actions in diabetic rats. This study investigated their combined effect relative to their individual treatments and lisinopril in rats with diabetic nephropathy. Streptozotocin (55mg/kg, i.p., once)-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Diabetic rats after 10 weeks developed nephropathy with discernible renal structural and functional changes as assessed in terms of increase in kidney weight to body weight ratio (KW/BW), and elevations of serum creatinine, urea and uric acid, which accompanied with elevated serum triglycerides and decreased high-density lipoproteins...
December 2014: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
G Salgueiro, L M Beltrán, R J Torres, J G Puig
BACKGROUND: Kidney function progressively deteriorates in patients with familial juvenile hyperuricemiac nephropathy (FJHN, OMIN 162000) and chronic renal disease is commonly associated to dyslipidemia. We report for the first time abrupt renal insufficiency in a patient with FJHN and hypertrygliceridemia following fenofibrate administration. CASE REPORT: A 53-year-old man was diagnosed clinically with FJHN at age 24 years which was subsequently confirmed by genotypic analysis of the UMOD gene at age 40 years...
2014: Nucleosides, Nucleotides & Nucleic Acids
Igbe Ighodaro, Omogbai Kelly Eric, Oyekan Adebayo
Diminished insulin sensitivity is a characteristic feature of various pathological conditions such as hypertension and activation of peroxisome proliferator activated receptor α (PPARα) has been shown to enhance insulin resistance and reduce capacity for glucose uptake in muscles. The present study was designed to evaluate the interactions of PPARα and GLUT4 in a model of hypertensive renal injury by studying deoxycorticosterone acetate (DOCA)-salt induced hypertension in wild-type (WT) and PPARα knockout (KO) mice...
2013: Nigerian Journal of Physiological Sciences: Official Publication of the Physiological Society of Nigeria
Yu Ah Hong, Ji Hee Lim, Min Young Kim, Tae Woo Kim, Yaeni Kim, Keun Suk Yang, Hoon Suk Park, Sun Ryoung Choi, Sungjin Chung, Hyung Wook Kim, Hye Won Kim, Bum Soon Choi, Yoon Sik Chang, Cheol Whee Park
Peroxisome proliferator-activated receptor (PPAR)-α, a lipid-sensing transcriptional factor, serves an important role in lipotoxicity. We evaluated whether fenofibrate has a renoprotective effect by ameliorating lipotoxicity in the kidney. Eight-week-old male C57BLKS/J db/m control and db/db mice, divided into four groups, received fenofibrate for 12 weeks. In db/db mice, fenofibrate ameliorated albuminuria, mesangial area expansion and inflammatory cell infiltration. Fenofibrate inhibited accumulation of intra-renal free fatty acids and triglycerides related to increases in PPARα expression, phosphorylation of AMP-activated protein kinase (AMPK), and activation of Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α)-estrogen-related receptor (ERR)-1α-phosphorylated acetyl-CoA carboxylase (pACC), and suppression of sterol regulatory element-binding protein (SREBP)-1 and carbohydrate regulatory element-binding protein (ChREBP)-1, key downstream effectors of lipid metabolism...
2014: PloS One
Xueying Zhao, Yuanyuan Zhang, Michelle Leander, Lingyun Li, Guoshen Wang, Nerimiah Emmett
Alpha(1D)-adrenergic receptor (α(1D)-AR) plays important roles in regulating physiological and pathological responses mediated by catecholamines, particularly in the cardiovascular and urinary systems. The present study was designed to investigate the expression profile of α(1D)-AR in the diabetic kidneys and its modulation by activation of peroxisome proliferator-activated receptors (PPARs). 12-week-old Zucker lean (ZL) and Zucker diabetic fatty (ZD) rats were treated with fenofibrate or rosiglitazone for 8-10 weeks...
2014: Journal of Diabetes Research
Jacob Koshy, Jency M Koshy, Satish Thomas, Gurvinder Kaur, Thomas Mathew
There remains a need for strategies that are effective in preventing diabetic retinopathy (DR) or slowing down its progression, which is safe, well-tolerated, and more effective, have a lower risk profile, easy to perform, have more predictable results with less morbidity than the current regimens. Physicians caring for diabetic patients not only need to maximize glycemic control, but also closely monitor and treat other systemic conditions. The consistency of clinical data from the fenofibrate studies showed consistent beneficial effects with fenofibrate in slowing the progression of DR...
October 2013: Middle East African Journal of Ophthalmology
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