Cilostazol Ameliorates Nephropathy in Type 1 Diabetic Rats Involving Improvement in Oxidative Stress and Regulation of TGF-β and NF-κB

Lee, Wen Chin; Chen, Hong Chen; Wang, Chih Ying; Lin, Pei; Ou, Tin Tsz; Chen, Chen Chang; Wen, Mei‐Chin; Wang, John; Lee, Huei Jane

doi:10.1271/bbb.90938

Cited by 41 publications

(44 citation statements)

References 30 publications

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“…Our present study established that mangiferin could provide protection against diabetic nephropathy (STZ; 65 mg/kg b.w. single dose) [54] via the reversal of the activation of PKCs, MAPKs, NF-κB as well as TGF-β1 and inhibiting both the extrinsic (mitochondrial independent) and intrinsic (mitochondrial dependent) apoptotic cell death involved in this pathophysiology. A number of recent studies showed that mangiferin could protect various organs including the kidney, probably because of its strong anti hyperglycemic effect and free radical (ROS) scavenging activity [55]–[57] in STZ-induce diabetic condition.…”

Section: Discussionmentioning

confidence: 99%

Mangiferin Attenuates Diabetic Nephropathy by Inhibiting Oxidative Stress Mediated Signaling Cascade, TNFα Related and Mitochondrial Dependent Apoptotic Pathways in Streptozotocin-Induced Diabetic Rats

2014

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Oxidative stress plays a crucial role in the progression of diabetic nephropathy in hyperglycemic conditions. It has already been reported that mangiferin, a natural C-glucosyl xanthone and polyhydroxy polyphenol compound protects kidneys from diabetic nephropathy. However, little is known about the mechanism of its beneficial action in this pathophysiology. The present study, therefore, examines the detailed mechanism of the beneficial action of mangiferin on STZ-induced diabetic nephropathy in Wister rats as the working model. A significant increase in plasma glucose level, kidney to body weight ratio, glomerular hypertrophy and hydropic changes as well as enhanced nephrotoxicity related markers (BUN, plasma creatinine, uric acid and urinary albumin) were observed in the experimental animals. Furthermore, increased oxidative stress related parameters, increased ROS production and decreased the intracellular antioxidant defenses were detected in the kidney. Studies on the oxidative stress mediated signaling cascades in diabetic nephropathy demonstrated that PKC isoforms (PKCα, PKCβ and PKCε), MAPKs (p38, JNK and ERK1/2), transcription factor (NF-κB) and TGF-β1 pathways were involved in this pathophysiology. Besides, TNFα was released in this hyperglycemic condition, which in turn activated caspase 8, cleaved Bid to tBid and finally the mitochorndia-dependent apoptotic pathway. In addition, oxidative stress also disturbed the proapoptotic-antiapoptotic (Bax and Bcl-2) balance and activated mitochorndia-dependent apoptosis via caspase 9, caspase 3 and PARP cleavage. Mangiferin treatment, post to hyperglycemia, successfully inhibited all of these changes and protected the cells from apoptotic death.

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Section: Discussionmentioning

confidence: 99%

Mangiferin Attenuates Diabetic Nephropathy by Inhibiting Oxidative Stress Mediated Signaling Cascade, TNFα Related and Mitochondrial Dependent Apoptotic Pathways in Streptozotocin-Induced Diabetic Rats

2014

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“…The protective effect of cilostazol could be attributed to the inhibitory effect on reactive oxygen species and superoxide generation as well as its positive effect on hydroxyl radical scavenging [Lee et al, 2010]. Further histopathological and ultrastructure studies are needed to evaluate the effect of cilostazol during the administration of amikacin and other AGs.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have referred to the inhibitory effect of cilostazol on reactive oxygen species and superoxide generation as well as hydroxyl radical scavenging action [Kim et al, 2002;Lee et al, 2010]. Transient (click) evoked (TEOAEs) and distortion product (DPOAEs) otoacoustic emissions (OAEs) can be registered in most normal human ears.…”

Section: Introductionmentioning

confidence: 99%

Cilostazol Effect on Amikacin-Induced Ototoxicity: An Experimental Study

El‐Anwar

Abdelmonem²,

Nada³

et al. 2016

Audiol Neurotol

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Objectives: To find out the possible protective effect of cilostazol against amikacin-induced ototoxicity. Methods: This study was carried out on 24 adult male rats classified into 4 equal groups of 6 animals each. (1) The control group was administered saline (1 ml/day, p.o.) for 14 days. (2) The amikacin group was administered amikacin (200 mg/kg, i.m.) once daily for 14 days. (3) The cilostazol-amikacin (14 days) group was administered cilostazol (30 mg/kg, p.o.) once daily and amikacin (200 mg/kg, i.m.) once daily for 14 days. (4) The cilostazol (28 days)-amikacin (14 days) group was administered cilostazol (30 mg/kg, p.o.) once daily for 28 days and amikacin (200 mg/kg, i.m.) once daily for 14 days. Changes in the transient evoked otoacoustic emissions (TEOAEs) in the 4 groups were interpreted statistically. Results: No reported significant differences in TEOAE levels were detected between the groups at the start of the study. In all frequency bands, TEOAEs disappeared after amikacin treatment in the amikacin-alone group and remained absent in the amikacin-cilostazol (14 days) group, while TEOAEs reappeared in the amikacin-cilostazol (28 days) group. Conclusion: Cilostazol treatment for 28 days had a protective effect against amikacin-induced ototoxicity in rats.

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“…In the trials reviewed above, cilostazol did not change body mass index, hemoglobin A1c, fasting glucose, and anklebrachial index [8,15,24,26]. Since blood glucose levels were not improved, good glycemic control in patients with diabetes is essential and is likely the rationale for appro-priate glycemic control as an inclusion criterion [15,26].…”

Section: Adverse Reactionsmentioning

confidence: 99%

“…Diabetic nephropathy can cause end-stage renal disease and is characterized by proteinuria with early increases in urinary albumin levels [7,8]. Reactive oxygen species, induced by hyperglycemia, cause both direct and indirect endothelial damage by modifying extracellular matrix pro-teins and by escalating the inflammatory response [9,10].…”

Section: Diabetic Nephropathymentioning

confidence: 99%

Effect of cilostazol in treating diabetes-associated microvascular complications

Asal

Wojciak

2017

Endocrine

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Purpose Cilostazol (Pletal), a phosphodiesterase-3 inhi-bitor, was approved in the United States in 1999 to reduce symptoms of intermittent claudication. Cyclic adenosine monophosphate levels increase from inhibition of phos-phodiesterase resulting in anti-platelet, anti-inflammatory, and vasodilatory effects. Diabetes mellitus is a chronic disease that causes endothelial and platelet dysfunction leading to both microvascular and macrovascular compli-cations. This mini-review highlights the emerging evidence suggesting benefits of using cilostazol in treating micro-vascular complications associated with diabetes mellitus. Methods A review of literature was conducted using PubMed and Embase databases focusing on cilostazol use in diabetes mellitus. Results Cilostazol demonstrated renoprotective effects in patients with diabetic nephropathy by reducing serum soluble adhesion molecule-1 and monocyte chemoattractant protein-1. Cilostazol's anti-inflammatory actions predictably attenuate glomerular damage from increased leukocyte adherence. Additionally, cilostazol delayed renal dysfunc-tion secondary to type 2 diabetes mellitus as albuminuria was reduced most likely resulting from inhibition of nuclear factor kappa-induced inflammatory and endothelial mar-kers. Cilostazol's antiinflammatory actions in addition to its vasodilatory actions relieved retinal hypoxia and decreased excessive production of retinal blood vessels suggesting benefit in diabetic retinopathy. Cilostazol did not improve

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Cilostazol Ameliorates Nephropathy in Type 1 Diabetic Rats Involving Improvement in Oxidative Stress and Regulation of TGF-β and NF-κB

Cited by 41 publications

References 30 publications

Mangiferin Attenuates Diabetic Nephropathy by Inhibiting Oxidative Stress Mediated Signaling Cascade, TNFα Related and Mitochondrial Dependent Apoptotic Pathways in Streptozotocin-Induced Diabetic Rats

Mangiferin Attenuates Diabetic Nephropathy by Inhibiting Oxidative Stress Mediated Signaling Cascade, TNFα Related and Mitochondrial Dependent Apoptotic Pathways in Streptozotocin-Induced Diabetic Rats

Cilostazol Effect on Amikacin-Induced Ototoxicity: An Experimental Study

Effect of cilostazol in treating diabetes-associated microvascular complications

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