scholarly journals Nephroprotective Effects of N-Acetylcysteine Amide against Contrast-Induced Nephropathy through Upregulating Thioredoxin-1, Inhibiting ASK1/p38MAPK Pathway, and Suppressing Oxidative Stress and Apoptosis in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Xuezhong Gong ◽  
Yiru Duan ◽  
Junli Zheng ◽  
Yiquan Wang ◽  
Guohua Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Contrast Induced Nephropathy ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
P38 Mapk Pathway ◽  
Thioredoxin 1 ◽  
Renal Tubular

Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury (AKI) due to apoptosis induced in renal tubular cells. Our previous study demonstrated the novel N-acetylcysteine amide (NACA); the amide form of N-acetyl cysteine (NAC) prevented renal tubular cells from contrast-induced apoptosis through inhibiting p38 MAPK pathway in vitro. In the present study, we aimed to compare the efficacies of NACA and NAC in preventing CIN in a well-established rat model and investigate whether thioredoxin-1 (Trx1) and apoptosis signal-regulating kinase 1 (ASK1) act as the potential activator for p38 MAPK. NACA significantly attenuated elevations of serum creatinine, blood urea nitrogen, and biomarkers of AKI. At equimolar concentration, NACA was more effective than NAC in reducing histological changes of renal tubular injuries. NACA attenuated activation of p38 MAPK signal, reduced oxidative stress, and diminished apoptosis. Furthermore, we demonstrated that contrast exposure resulted in Trx1 downregulation and increased ASK1/p38 MAPK phosphorylation, which could be reversed by NACA and NAC. To our knowledge, this is the first report that Trx1 and ASK1 are involved in CIN. Our study highlights a renal protective role of NACA against CIN through modulating Trx1 and ASK1/p38 MAPK pathway to result in the inhibition of apoptosis among renal cells.

scholarly journals The Suppression of Pin1-Alleviated Oxidative Stress through the p38 MAPK Pathway in Ischemia- and Reperfusion-Induced Acute Kidney Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Xiaojie Zhao ◽  
Dan Wang ◽  
Shanshan Wan ◽  
Xiuheng Liu ◽  
Wei Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Kidney Injury ◽  
Ischemia And Reperfusion ◽  
P38 Mapk Pathway

Background. Pin1, as the peptidyl-prolyl isomerase, plays a vital role in cellular processes. However, whether it has a regulatory effect on renal ischemia and reperfusion (I/R) injury still remains unknown. Methods. The hypoxia/reoxygenation (H/R) model in human kidney (HK-2) cells and the I/R model in rats were assessed to investigate the role of Pin1 on I/R-induced acute kidney injury. Male Sprague-Dawley rats were used to establish the I/R model for 15, 30, and 45 min ischemia and then 24 h reperfusion, with or without the Pin1 inhibitor, to demonstrate the role of Pin1 in acute kidney injury. HK-2 cells were cultured and experienced the H/R model to identify the molecular mechanisms involved. Results. In this study, we found that Pin1 and oxidative stress were obviously increased after renal I/R. Inhibition of Pin1 with juglone decreased renal structural and functional injuries, as well as oxidative stress. Besides, Pin1 inhibition with the inhibitor, juglone, or the small interfering RNA showed significant reduction on oxidative stress markers caused by the H/R process in vitro. Furthermore, the results indicated that the expression of p38 MAPK was increased during H/R in vitro and Pin1 inhibition could reduce the increased expression of p38 MAPK. Conclusion. Our results illustrated that Pin1 aggravated renal I/R injury via elevating oxidative stress through activation of the p38 MAPK pathway. These findings indicated that Pin1 might become the potential treatment for renal I/R injury.

Tougu Xiaotong capsules may inhibit p38 MAPK pathway-mediated inflammation: In vivo and in vitro verification

2020 ◽  
Vol 249 ◽  
pp. 112390 ◽  
Author(s):  
Xihai Li ◽  
Zhenli Zhang ◽  
Wenna Liang ◽  
Jianwei Zeng ◽  
Xiang Shao ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Mapk Pathway ◽  
P38 Mapk Pathway

scholarly journals Palmitate aggravates proteinuria-induced cell death and inflammation via CD36-inflammasome axis in the proximal tubular cells of obese mice

2018 ◽  
Vol 315 (6) ◽  
pp. F1720-F1731 ◽  
Author(s):  
Lung-Chih Li ◽  
Jenq-Lin Yang ◽  
Wen-Chin Lee ◽  
Jin-Bor Chen ◽  
Chien-Te Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Tubular Injury ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Caspase 1 ◽  
Proximal Tubular ◽  
Renal Tubular ◽  
Nlrp3 Inflammasomes

High levels of serum free fatty acids (FFAs) and proteinuria have been implicated in the pathogenesis of obesity-related nephropathy. CD36, a class B scavenger receptor, is highly expressed in the renal proximal tubules and mediates FFA uptake. It is not clear whether FFA- and proteinuria-mediated CD36 activation coordinates NLRP3 inflammasomes to induce renal tubular injury and inflammation. In this study, we investigated the roles of CD36 and NLRP3 inflammasomes in FFA-induced renal injury in high-fat diet (HFD)-induced obesity. HFD-fed C57BL/6 mice and palmitate-treated HK2 renal tubular cells were used as in vivo and in vitro models. Immunohistochemical staining showed that CD36, IL-1β, and IL-18 levels increased progressively in the kidneys of HFD-fed mice. Sulfo- N-succinimidyl oleate (SSO), a CD36 inhibitor, attenuated the HFD-induced upregulation of NLRP3, IL-1β, and IL-18 and suppressed the colocalization of NLRP3 and ASC in renal tubular cells. In vitro, SSO abolished the palmitate-induced activation of IL-1β, IL-18, and caspase-1 in HK2 proximal tubular cells. Furthermore, treatment with SSO and the knockdown of caspase-1 expression by siRNA both inhibited palmitate-induced cell death and apoptosis in HK2 cells. Collectively, palmitate causes renal tubular inflammation, cell death, and apoptosis via the CD36/NLRP3/caspase-1 axis, which may explain, at least in part, the mechanism underlying FFA-related renal tubular injury. The blockade of CD36-induced cellular processes is therefore a promising strategy for treating obesity-related nephropathy.

scholarly journals Vitamin C attenuates the toxic effect of aristolochic acid on renal tubular cells via decreasing oxidative stress-mediated cell death pathways

2015 ◽  
Vol 12 (4) ◽  
pp. 6086-6092 ◽  
Author(s):  
TSAI-KUN WU ◽  
CHYOU-WEI WEI ◽  
YING-RU PAN ◽  
SHUR-HUEIH CHERNG ◽  
WEI-JUNG CHANG ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Vitamin C ◽  
Toxic Effect ◽  
Aristolochic Acid ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Cell Death Pathways ◽  
Renal Tubular

scholarly journals Caspofungin is less nephrotoxic than amphotericin B in vitro and predominantly damages distal renal tubular cells

2005 ◽  
Vol 20 (10) ◽  
pp. 2071-2079 ◽  
Author(s):  
Binytha Wegner ◽  
Patrick Baer ◽  
Stefan Gauer ◽  
Gerhard Oremek ◽  
Ingeborg A. Hauser ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular
Sign in / Sign up

Export Citation Format

Share Document