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Open AccessArticle

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

1
Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India
2
Department of Chemical Technology, University of Calcutta, Kolkata 700009, India
3
Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy
*
Authors to whom correspondence should be addressed.
Present address: Department of Pharmaceutical Technology, University of North Bengal, Darjeeling 734013, India.
Int. J. Mol. Sci. 2019, 20(8), 2027; https://doi.org/10.3390/ijms20082027
Received: 26 March 2019 / Revised: 20 April 2019 / Accepted: 23 April 2019 / Published: 24 April 2019
(This article belongs to the Section Bioactives and Nutraceuticals)
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. View Full-Text
Keywords: antioxidant; apoptosis; cadmium; oxidative stress; rosmarinic acid antioxidant; apoptosis; cadmium; oxidative stress; rosmarinic acid
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MDPI and ACS Style

Joardar, S.; Dewanjee, S.; Bhowmick, S.; Dua, T.K.; Das, S.; Saha, A.; De Feo, V. Rosmarinic Acid Attenuates Cadmium-Induced Nephrotoxicity via Inhibition of Oxidative Stress, Apoptosis, Inflammation and Fibrosis. Int. J. Mol. Sci. 2019, 20, 2027.

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