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https://www.readbyqxmd.com/read/28805491/intermedin-inhibits-unilateral-ureteral-obstruction-induced-oxidative-stress-via-nadph-oxidase-nox4-and-camp-dependent-mechanisms
#1
Xi Qiao, Lihua Wang, Yanhong Wang, Xiaole Su, Yue Qi, Yun Fan, Zhiqiang Peng
NADPH oxidase Nox4-derived reactive oxygen species (ROS) play important roles in renal fibrosis. Our previous study demonstrated that intermedin (IMD) alleviated unilateral ureteral obstruction (UUO)-induced renal fibrosis by inhibition of ROS. However, the precise mechanisms remain unclear. Herein, we investigated the effect of IMD on Nox4 expression and NADPH oxidase activity in rat UUO model, and explored if these effect were achieved through cAMP-PKA pathway, the important post-receptor signal transduction pathway of IMD, in TGF-β1-stimulated rat proximal tubular cell (NRK-52E)...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28774949/renoprotective-effect-of-topiroxostat-via-antioxidant-activity-in-puromycin-aminonucleoside-nephrosis-rats
#2
Yosuke Kawamorita, Takeshi Shiraishi, Yoshifuru Tamura, Takanori Kumagai, Shigeru Shibata, Yoshihide Fujigaki, Makoto Hosoyamada, Takahiko Nakagawa, Shunya Uchida
Topiroxostat is a novel inhibitor of xanthine oxidase, and is postulated to exert a renoprotective effect. Puromycin aminonucleoside nephrosis (PAN) is a rat model of minimal change nephrotic syndrome. In this study, we examined whether topiroxostat ameliorates the kidney injury in PAN rats that was induced by a single intraperitoneal injection of PA (100 mg/kg body weight). Rats were divided into four groups: control rats, PAN rats, control rats treated with topiroxostat (1.0 mg/kg/day), and PAN rats treated with topiroxostat...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28771600/eicosapentaenoic-acid-prevents-arterial-calcification-in-klotho-mutant-mice
#3
Kazufumi Nakamura, Daiji Miura, Yukihiro Saito, Kei Yunoki, Yasushi Koyama, Minoru Satoh, Megumi Kondo, Kazuhiro Osawa, Omer F Hatipoglu, Toru Miyoshi, Masashi Yoshida, Hiroshi Morita, Hiroshi Ito
BACKGROUND: The klotho gene was identified as an "aging-suppressor" gene that accelerates arterial calcification when disrupted. Serum and vascular klotho levels are reduced in patients with chronic kidney disease, and the reduced levels are associated with arterial calcification. Intake of eicosapentaenoic acid (EPA), an n-3 fatty acid, reduces the risk of fatal coronary artery disease. However, the effects of EPA on arterial calcification have not been fully elucidated. The aim of this study was to determine the effect of EPA on arterial calcification in klotho mutant mice...
2017: PloS One
https://www.readbyqxmd.com/read/28753620/treatment-combining-aliskiren-with-paricalcitol-is-effective-against-progressive-renal-tubulointerstitial-fibrosis-via-dual-blockade-of-intrarenal-renin
#4
Sungjin Chung, Soojeong Kim, Minyoung Kim, Eun Sil Koh, Seok Joon Shin, Cheol Whee Park, Yoon Sik Chang, Ho-Shik Kim
The aim of this study was to assess any potential additive effects of a treatment combining aliskiren with paricalcitol on reducing renal fibrosis. C57BL/6J mice were treated individually with aliskiren and/or paricalcitol until 7 days after initiation of unilateral ureteral obstruction (UUO).In obstructed kidneys of UUO mice, monotherapy with aliskiren or paricalcitol significantly attenuated interstitial fibrosis, collagen IV accumulation, and α-smooth muscle actin- and terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling-positive cells...
2017: PloS One
https://www.readbyqxmd.com/read/28739802/tgf-%C3%AE-1-regulates-the-expression-and-transcriptional-activity-of-taz-via-a-smad3-independent-myocardin-related-transcription-factor-mediated-mechanism
#5
Maria Zena Miranda, Janne Folke Bialik, Pam Speight, Qinghong Dan, Tony Yeung, Katalin Szászi, Stine F Pedersen, András Kapus
Hippo pathway transcriptional coactivators TAZ and YAP and the TGF-β1 (TGFβ) effector Smad3 regulate a common set of genes, can physically interact and exhibit multilevel crosstalk regulating cell fate-determining and fibrogenic pathways. However, a key aspect of this crosstalk, TGFβ-mediated regulation of TAZ or YAP expression remains uncharacterized. Here, we show that TGFβ induces robust TAZ but not YAP protein expression in both mesenchymal and epithelial cells. TAZ levels, and to a lesser extent YAP levels, also increased during experimental kidney fibrosis...
July 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28703736/nephroprotective-effects-of-saponins-from-leaves-of-panax-quinquefolius-against-cisplatin-induced-acute-kidney-injury
#6
Zhi-Na Ma, Yan-Zi Li, Wei Li, Xiao-Tong Yan, Ge Yang, Jing Zhang, Li-Chun Zhao, Li-Min Yang
Although cisplatin is an anticancer drug that has activity against malignant tumor, it often causes nephrotoxicity. Previous reports have confirmed that the saponins from the leaves of P. quinquefolium (PQS) exerted many pharmacological activities. However, the renoprotective effects of PQS were still unknown. The purpose of the present research was to discuss renoprotective effect of PQS in a mouse model of cisplatin-induced acute kidney injury (AKI). The levels of blood urea nitrogen (BUN) and serum creatinine (CRE) were evidently increased in cisplatin-intoxicated mice, which were reversed by PQS...
July 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28686724/dipeptidyl-peptidase-4-inhibitor-gemigliptin-protects-against-vascular-calcification-in-an-experimental-chronic-kidney-disease-and-vascular-smooth-muscle-cells
#7
Soon-Youn Choi, Hye-Myung Ryu, Eun-Joo Oh, Ji-Young Choi, Jang-Hee Cho, Chan-Duck Kim, Yong-Lim Kim, Sun-Hee Park
Although dipeptidyl peptidase-4 inhibitors, a class of antidiabetic drugs, have various pleiotropic effects, it remains undetermined whether gemigliptin has a beneficial effect on vascular calcification. Therefore, this study was performed to evaluate the effect of gemigliptin on vascular calcification in a rat model of adenine-induced chronic kidney disease and in cultured vascular smooth muscle cells. Gemigliptin attenuated calcification of abdominal aorta and expression of RUNX2 in adenine-induced chronic kidney disease rats...
2017: PloS One
https://www.readbyqxmd.com/read/28473473/the-emerging-role-of-nadph-oxidase-nox5%C3%A2-in-vascular-disease
#8
REVIEW
Jay C Jha, Anna M D Watson, Geetha Mathew, Lisanne C de Vos, Karin Jandeleit-Dahm
Oxidative stress is a consequence of up-regulation of pro-oxidant enzyme-induced reactive oxygen species (ROS) production and concomitant depletion of antioxidants. Elevated levels of ROS act as an intermediate and are the common denominator for various diseases including diabetes-associated macro-/micro-vascular complications and hypertension. A range of enzymes are capable of generating ROS, but the pro-oxidant enzyme family, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs), are the only enzymes known to be solely dedicated to ROS generation in the vascular tissues, kidney, aortas and eyes...
May 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28438648/the-superoxide-dismutase-mimetic-tempol-blunts-diabetes-induced-upregulation-of-nadph-oxidase-and-endoplasmic-reticulum-stress-in-a-rat-model-of-diabetic-nephropathy
#9
Miles J De Blasio, Anand Ramalingam, Anh H Cao, Darnel Prakoso, Ji-Ming Ye, Raelene Pickering, Anna M D Watson, Judy B de Haan, David M Kaye, Rebecca H Ritchie
Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Male Sprague-Dawley rats were injected intravenously with a single bolus of streptozotocin (55mg/kg) to induce type 1 diabetes...
July 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28396118/superoxide-and-hydrogen-peroxide-counterregulate-myogenic-contractions-in-renal-afferent-arterioles-from-a-mouse-model-of-chronic-kidney-disease
#10
Lingli Li, En Yin Lai, Zaiming Luo, Glenn Solis, Kathy K Griendling, W Robert Taylor, Pedro A Jose, Anton Wellsten, William J Welch, Christopher S Wilcox
Myogenic contractions protect kidneys from barotrauma but are impaired in chronic kidney disease (CKD). Since myogenic contractions are enhanced by superoxide but impaired by hydrogen peroxide, we tested the hypothesis that they are counterregulated by superoxide and H2O2 from NOX2/p47phox and/or NOX4/POLDIP2 in CKD. Myogenic contraction in isolated perfused afferent arterioles from mice with surgical 5/6 nephrectomy or sham operations fed a 6% sodium chloride diet was measured directly while superoxide and H2O2 were measured by fluorescence microscopy...
April 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28395989/naringin-ameliorates-diabetic-nephropathy-by-inhibiting-nadph-oxidase-4
#11
Junwei Zhang, Suxia Yang, Huicong Li, Fang Chen, Jun Shi
Naringin, a naturally flavanone glycoside, has been previously demonstrated to alleviate diabetic kidney disease by inhibiting oxidative stress and inflammatory reaction. However, the underlying mechanism of naringin in diabetic nephropathy (DN) has not been fully elucidated. Here, the beneficial effect of naringin on DN in streptozotocin (STZ)-induced DN rats and high glucose (HG)-induced podocytes and its underlying mechanism were elaborated. The result revealed that naringin alleviated STZ-induced renal dysfunction and injury in DN rats, relieved STZ-induced oxidative stress in vivo and inhibited HG-induced apoptosis and reactive oxygen species level i20n vitro...
June 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28323024/ppar%C3%AE-activation-by-mhy908-attenuates-age-related-renal-inflammation-through-modulation-of-the-ros-akt-foxo1-pathway
#12
Ye Ra Kim, Eun Kyeong Lee, Dae Hyun Kim, Kyung Mok Kim, Bonggi Lee, Hye Jin An, June Whoun Park, Kyoung Mi Moon, Min Hi Park, Ki Wung Chung, Ji Young Park, Seong Jin Kim, Hwi Young Yun, Sujin Son, Pusoon Chun, Hyung Ryong Moon, Hae Young Chung
2-[4-(5-Chlorobenzothiazothiazol-2-yl)phenoxy]-2-methyl-propionic acid (MHY908) has been shown to prevent insulin resistance-induced hyperinsulinemia in aged rats. However, the mechanism underlying MHY908-mediated amelioration of renal inflammation with insulin resistance during aging remains unknown. This study investigated the effects of MHY908 on age-related changes in the IRS/Akt/forkhead box (FoxO) 1 signaling pathway in the kidneys of aged rats and HEK293T cells. Experiments were performed in young, old, and MHY908-fed old rats (1mg or 3mg/kg/day MHY908 for 4 weeks)...
June 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28249219/psoriasis-like-inflammation-leads-to-renal-dysfunction-via-upregulation-of-nadph-oxidases-and-inducible-nitric-oxide-synthase
#13
Naif O Al-Harbi, Ahmed Nadeem, Mushtaq A Ansari, Mohammed M Al-Harbi, Moureq R Alotaibi, Abdulaziz M S AlSaad, Sheikh F Ahmad
Psoriatic patients have systemic inflammation as well as oxidative stress, which are associated with cardiovascular disorders such as atherosclerosis, hypertension myocardial infarction, and stroke. Psoriasis has also been shown to be associated with kidney disease in several studies. Both disorders also have strong component of oxidative stress which usually emanates from NADPH oxidases (NOXs) and inducible nitric oxide synthase (iNOS). However, whether psoriatic inflammation leads to renal oxidative stress and dysfunction remains unexplored...
May 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28211114/magnesium-lithospermate-b-from-salvia-miltiorrhiza-bunge-ameliorates-aging-induced-renal-inflammation-and-senescence-via-nadph-oxidase-mediated-reactive-oxygen-generation
#14
Chan Hum Park, Sung Ho Shin, Eun Kyeong Lee, Dae Hyun Kim, Min-Jo Kim, Seong-Soo Roh, Takako Yokozawa, Hae Young Chung
The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age-related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2- or 8-mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species...
February 16, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28188286/hydrogen-sulfide-inhibits-high-glucose-induced-nadph-oxidase-4-expression-and-matrix-increase-by-recruiting-inducible-nitric-oxide-synthase-in-kidney-proximal-tubular-epithelial-cells
#15
Hak Joo Lee, Doug Yoon Lee, Meenalakshmi M Mariappan, Denis Feliers, Goutam Ghosh-Choudhury, Hanna E Abboud, Yves Gorin, Balakuntalam S Kasinath
High-glucose increases NADPH oxidase 4 (NOX4) expression, reactive oxygen species generation, and matrix protein synthesis by inhibiting AMP-activated protein kinase (AMPK) in renal cells. Because hydrogen sulfide (H2S) inhibits high glucose-induced matrix protein increase by activating AMPK in renal cells, we examined whether H2S inhibits high glucose-induced expression of NOX4 and matrix protein and whether H2S and NO pathways are integrated. High glucose increased NOX4 expression and activity at 24 h in renal proximal tubular epithelial cells, which was inhibited by sodium hydrosulfide (NaHS), a source of H2S...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28165467/apx-115-a-first-in-class-pan-nadph-oxidase-nox-inhibitor-protects-db-db-mice-from-renal-injury
#16
Jin Joo Cha, Hye Sook Min, Ki Tae Kim, Jung Eun Kim, Jung Yeon Ghee, Hyun Wook Kim, Ji Eun Lee, Jee Young Han, Gayoung Lee, Hun Joo Ha, Yun Soo Bae, Sae Rom Lee, Sung Hwan Moon, Sung Chan Lee, Ganghyun Kim, Young Sun Kang, Dae Ryong Cha
Recent studies have suggested that renal Nox is important in the progression of diabetic nephropathy. Therefore, we investigated the effect of a novel pan-NOX-inhibitor, APX-115, on diabetic nephropathy in type 2 diabetic mice. Eight- week-old db/m and db/db mice were treated with APX-115 for 12 weeks. APX-115 was administered by oral gavage at a dose of 60 mg/kg per day. To compare the effects of APX-115 with a dual Nox1/Nox4 inhibitor, db/db mice were treated with GKT137831 according to the same protocol...
April 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28138709/trpm8-downregulation-by-angiotensin-ii-in-vascular-smooth-muscle-cells-is-involved-in-hypertension
#17
Fang Huang, Min Ni, Jing-Ming Zhang, Dong-Jie Li, Fu-Ming Shen
Angiotensin II (Ang II)-induced injury of vascular smooth muscle cells (VSMCs) serves an important role in hypertension and other cardiovascular disorders. Transient receptor potential melastatin 8 (TRPM8) is a thermally‑regulated Ca2+‑permeable channel that is activated by reduced body temperature. Although several recent studies have revealed the regulatory effect of TRPM8 in vascular tone and hypertension, the precise role of TRPM8 in dysfunction of vascular smooth muscle cells (VSMCs) induced by Ang II remains elusive...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28132913/nebivolol-prevents-ethanol-induced-reactive-oxygen-species-generation-and-lipoperoxidation-in-the-rat-kidney-by-regulating-nadph-oxidase-activation-and-expression
#18
Gabriel T do Vale, Natália A Gonzaga, Janaina A Simplicio, Carlos R Tirapelli
We studied whether the β1-adrenergic antagonist nebivolol would prevent ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat renal cortex. Male Wistar rats were treated with ethanol (20% v/v) for 2 weeks. Nebivolol (10mg/kg/day; p.o. gavage) prevented both the increase in superoxide anion (O2(-)) generation and thiobarbituric acid reactive substances (TBARS) concentration induced by ethanol in the renal cortex. Ethanol decreased nitrate/nitrite (NOx) concentration in the renal cortex, and nebivolol prevented this response...
March 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28116040/mitotempo-prevents-oxalate-induced-injury-in-nrk-52e-cells-via-inhibiting-mitochondrial-dysfunction-and-modulating-oxidative-stress
#19
Jiaqiao Zhang, Qing Wang, Chuou Xu, Yuchao Lu, Henglong Hu, Baolong Qin, Yufeng Wang, Deng He, Cong Li, Xiao Yu, Shaogang Wang, Jihong Liu
As one of the major risks for urolithiasis, hyperoxaluria can be caused by genetic defect or dietary intake. And high oxalate induced renal epithelial cells injury is related to oxidative stress and mitochondrial dysfunction. Here, we investigated whether MitoTEMPO, a mitochondria-targeted antioxidant, could protect against oxalate mediated injury in NRK-52E cells via inhibiting mitochondrial dysfunction and modulating oxidative stress. MitoSOX Red was used to determine mitochondrial ROS (mtROS) production...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28063381/brd4-inhibition-attenuates-unilateral-ureteral-obstruction-induced-fibrosis-by-blocking-tgf-%C3%AE-mediated-nox4-expression
#20
Baoshang Zhou, Jiao Mu, Yi Gong, Caibao Lu, Youguang Zhao, Ting He, Zhexue Qin
Uncovering new therapeutic targets for renal fibrosis holds promise for the treatment of chronic kidney diseases. Bromodomain and extra-terminal (BET) protein inhibitors have been shown to effectively ameliorate pathological fibrotic responses. However, the pharmacological effects and underlying mechanisms of these inhibitors in renal fibrosis remain elusive. In this study, we determined that the inhibition of Brd4, a BET family member, with a selective potent chemical inhibitor, JQ1, could prevent the development of renal fibrosis and block the progression of fibrosis in rats that have undergone unilateral ureteral obstruction (UUO)...
April 2017: Redox Biology
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