scholarly journals Rosmarinic Acid Attenuates Cadmium-Induced Nephrotoxicity via Inhibition of Oxidative Stress, Apoptosis, Inflammation and Fibrosis

2019 ◽  
Vol 20 (8) ◽  
pp. 2027 ◽  
Author(s):  
Swarnalata Joardar ◽  
Saikat Dewanjee ◽  
Shovonlal Bhowmick ◽  
Tarun K. Dua ◽  
Sonjit Das ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rosmarinic Acid ◽  
Protective Mechanism ◽  
Renal Cells ◽  
Apoptotic Effect ◽  
Proximal Tubular Epithelial Cells ◽  
Histological Data ◽  
Proximal Tubular ◽  
Nadph Oxidase Activation ◽  
Tgf Β1

The present investigation was executed to reveal the protective mechanism of rosmarinic acid (RA) against cadmium (Cd)-induced nephrotoxicity. RA exhibited a concentration-dependent anti-apoptotic effect against CdCl2 in isolated mouse proximal tubular epithelial cells. Cd treatment significantly (p < 0.01) imparted oxidative stress to the renal cells via excessive ROS production, triggering NO level, NADPH oxidase activation, and impairment of cellular redox defense system. Cd-mediated oxidative stress significantly (p < 0.01) endorsed apoptosis to the murine kidney cells by triggering NF-κB/PKC-δ/TNFR2 activation. In addition, CdCl2 induced renal fibrosis by triggering TGF-β1/SMAD3/α-SMA/collagen signaling within renal cells. On the other hand, RA significantly (p < 0.05–0.01) attenuated Cd-provoked oxidative stress and associated pathological signal transduction in murine renal cells. RA treatment also could significantly (p < 0.05–0.01) reciprocate Cd-mediated pathological changes in blood and urine parameters in mice. In addition, histological data supported the pharmacological findings. In silico chemometric analyses predicted the possible interactions between RA and different signal proteins and anticipated drug-likeness characteristics of RA. Hence, RA can potentially be applied as a therapeutic agent to treat Cd-mediated nephrotoxicity in future.

scholarly journals Carnosic Acid Attenuates Cadmium Induced Nephrotoxicity by Inhibiting Oxidative Stress, Promoting Nrf2/HO-1 Signalling and Impairing TGF-β1/Smad/Collagen IV Signalling

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4176 ◽  
Author(s):  
Sonjit Das ◽  
Saikat Dewanjee ◽  
Tarun K. Dua ◽  
Swarnalata Joardar ◽  
Pratik Chakraborty ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Collagen Iv ◽  
Carnosic Acid ◽  
Protective Mechanism ◽  
Related Factor ◽  
Renal Cells ◽  
Cdcl2 Treatment ◽  
Tgf Β1

Cadmium (Cd) imparts nephrotoxicity via triggering oxidative stress and pathological signal transductions in renal cells. The present study was performed to explore the protective mechanism of carnosic acid (CA), a naturally occurring antioxidant compound, against cadmium chloride (CdCl2)-provoked nephrotoxicity employing suitable in vitro and in vivo assays. CA (5 µM) exhibited an anti-apoptotic effect against CdCl2 (40 µM) in normal kidney epithelial (NKE) cells evidenced from cell viability, image, and flow cytometry assays. In this study, CdCl2 treatment enhanced oxidative stress by triggering free radical production, suppressing the endogenous redox defence system, and inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) activation in NKE cells and mouse kidneys. Moreover, CdCl2 treatment significantly endorsed apoptosis and fibrosis via activation of apoptotic and transforming growth factor (TGF)-β1/mothers against decapentaplegic homolog (Smad)/collagen IV signalling pathways, respectively. In contrast, CA treatment significantly attenuated Cd-provoked nephrotoxicity via inhibiting free radicals, endorsing redox defence, suppressing apoptosis, and inhibiting fibrosis in renal cells in both in vitro and in vivo systems. In addition, CA treatment significantly (p < 0.05–0.01) restored blood and urine parameters to near-normal levels in mice. Histological findings further confirmed the protective role of CA against Cd-mediated nephrotoxicity. Molecular docking predicted possible interactions between CA and Nrf2/TGF-β1/Smad/collagen IV. Hence, CA was found to be a potential therapeutic agent to treat Cd-mediated nephrotoxicity.

scholarly journals Uptake of Polymyxin B into Renal Cells

2014 ◽  
Vol 58 (7) ◽  
pp. 4200-4202 ◽  
Author(s):  
Kamilia Abdelraouf ◽  
Kai-Tai Chang ◽  
Taijun Yin ◽  
Ming Hu ◽  
Vincent H. Tam
Keyword(s):  
Apical Membrane ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Tubular Epithelial Cells ◽  
Renal Cells ◽  
Kidney Cell Line ◽  
Gram Negative ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
B Uptake

ABSTRACTPolymyxin B is increasingly used as a treatment of last resort against multidrug-resistant Gram-negative infections. Using a mammalian kidney cell line, we demonstrated that polymyxin B uptake into proximal tubular epithelial cells was saturable and occurred primarily through the apical membrane, suggesting the involvement of transporters in the renal uptake of polymyxin B. Megalin might play a role in the uptake and accumulation of polymyxin B into renal cells.

High glucose‐induced oxidative stress causes apoptosis in proximal tubular epithelial cells and is mediated by multiple caspases

2003 ◽  
Vol 17 (8) ◽  
pp. 1-21 ◽  
Author(s):  
David A. Allen ◽  
Steven M. Harwood ◽  
Mira Varagunam ◽  
Martin J. Raftery ◽  
Muhammad M. Yaqoob
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
High Glucose ◽  
Tubular Epithelial Cells ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular

scholarly journals Edaravone-Loaded Mesoscale Nanoparticles Treat Cisplatin-Induced Acute Kidney Injury

2020 ◽  
Author(s):  
Ryan M. Williams ◽  
Janki Shah ◽  
Elizabeth Mercer ◽  
Helen S. Tian ◽  
Justin M. Cheung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Epithelial Cells ◽  
Kidney Injury ◽  
Tubular Epithelial Cells ◽  
Co Morbidity ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Tumor Accumulation ◽  
Renal Proximal Tubular

AbstractCisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. In our prior work, we developed a highly-selective kidney-targeted mesoscale nanoparticle (MNP) that accumulates primarily in the renal proximal tubular epithelial cells while exhibiting no toxicity. Here, we found that MNPs exhibit renal-selective targeting in multiple mouse models of tumor growth with virtually no tumor accumulation. We then evaluated the therapeutic efficacy of MNPs loaded with the reactive oxygen species scavenger edaravone in a mouse model of CI-AKI. We found a marked and significant therapeutic effect with this approach as compared to free drug or empty control MNPs, including improved renal function, histology, and diminution of oxidative stress. These results indicated that renal-selective MNP edaravone delivery holds substantial potential in the treatment of acute kidney injury among patients undergoing cisplatin-based chemotherapy.

Sign in / Sign up

Export Citation Format

Share Document