Carnosic Acid Attenuates Cadmium Induced Nephrotoxicity by Inhibiting Oxidative Stress, Promoting Nrf2/HO-1 Signalling and Impairing TGF-β1/Smad/Collagen IV Signalling
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 (CdCl<sub>2&...
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MDPI AG
2019-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/22/4176 |
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| author | Sonjit Das Saikat Dewanjee Tarun K. Dua Swarnalata Joardar Pratik Chakraborty Shovonlal Bhowmick Achintya Saha Simanta Bhattacharjee Vincenzo De Feo |
| author_facet | Sonjit Das Saikat Dewanjee Tarun K. Dua Swarnalata Joardar Pratik Chakraborty Shovonlal Bhowmick Achintya Saha Simanta Bhattacharjee Vincenzo De Feo |
| author_sort | Sonjit Das |
| collection | DOAJ |
| description | 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 (CdCl<sub>2</sub>)-provoked nephrotoxicity employing suitable in vitro and in vivo assays. CA (5 µM) exhibited an anti-apoptotic effect against CdCl<sub>2</sub> (40 µM) in normal kidney epithelial (NKE) cells evidenced from cell viability, image, and flow cytometry assays. In this study, CdCl<sub>2</sub> 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, CdCl<sub>2</sub> 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 (<i>p</i> < 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. |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-13T04:12:16Z |
| publishDate | 2019-11-01 |
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| spelling | doaj.art-f51853ca458f47f1b3717443cd3707392022-12-21T23:59:59ZengMDPI AGMolecules1420-30492019-11-012422417610.3390/molecules24224176molecules24224176Carnosic Acid Attenuates Cadmium Induced Nephrotoxicity by Inhibiting Oxidative Stress, Promoting Nrf2/HO-1 Signalling and Impairing TGF-β1/Smad/Collagen IV SignallingSonjit Das0Saikat Dewanjee1Tarun K. Dua2Swarnalata Joardar3Pratik Chakraborty4Shovonlal Bhowmick5Achintya Saha6Simanta Bhattacharjee7Vincenzo De Feo8Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, IndiaAdvanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, IndiaAdvanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, IndiaAdvanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, IndiaAdvanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, IndiaDepartment of Chemical Technology, University of Calcutta, Kolkata 700009, IndiaDepartment of Chemical Technology, University of Calcutta, Kolkata 700009, IndiaAdvanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, IndiaDepartment of Pharmacy, University of Salerno, 84084 Fisciano, ItalyCadmium (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 (CdCl<sub>2</sub>)-provoked nephrotoxicity employing suitable in vitro and in vivo assays. CA (5 µM) exhibited an anti-apoptotic effect against CdCl<sub>2</sub> (40 µM) in normal kidney epithelial (NKE) cells evidenced from cell viability, image, and flow cytometry assays. In this study, CdCl<sub>2</sub> 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, CdCl<sub>2</sub> 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 (<i>p</i> < 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.https://www.mdpi.com/1420-3049/24/22/4176antioxidantcadmium chloridecarnosic acidmolecular dockingoxidative stress |
| spellingShingle | Sonjit Das Saikat Dewanjee Tarun K. Dua Swarnalata Joardar Pratik Chakraborty Shovonlal Bhowmick Achintya Saha Simanta Bhattacharjee Vincenzo De Feo Carnosic Acid Attenuates Cadmium Induced Nephrotoxicity by Inhibiting Oxidative Stress, Promoting Nrf2/HO-1 Signalling and Impairing TGF-β1/Smad/Collagen IV Signalling Molecules antioxidant cadmium chloride carnosic acid molecular docking oxidative stress |
| title | Carnosic Acid Attenuates Cadmium Induced Nephrotoxicity by Inhibiting Oxidative Stress, Promoting Nrf2/HO-1 Signalling and Impairing TGF-β1/Smad/Collagen IV Signalling |
| title_full | Carnosic Acid Attenuates Cadmium Induced Nephrotoxicity by Inhibiting Oxidative Stress, Promoting Nrf2/HO-1 Signalling and Impairing TGF-β1/Smad/Collagen IV Signalling |
| title_fullStr | Carnosic Acid Attenuates Cadmium Induced Nephrotoxicity by Inhibiting Oxidative Stress, Promoting Nrf2/HO-1 Signalling and Impairing TGF-β1/Smad/Collagen IV Signalling |
| title_full_unstemmed | Carnosic Acid Attenuates Cadmium Induced Nephrotoxicity by Inhibiting Oxidative Stress, Promoting Nrf2/HO-1 Signalling and Impairing TGF-β1/Smad/Collagen IV Signalling |
| title_short | Carnosic Acid Attenuates Cadmium Induced Nephrotoxicity by Inhibiting Oxidative Stress, Promoting Nrf2/HO-1 Signalling and Impairing TGF-β1/Smad/Collagen IV Signalling |
| title_sort | carnosic acid attenuates cadmium induced nephrotoxicity by inhibiting oxidative stress promoting nrf2 ho 1 signalling and impairing tgf β1 smad collagen iv signalling |
| topic | antioxidant cadmium chloride carnosic acid molecular docking oxidative stress |
| url | https://www.mdpi.com/1420-3049/24/22/4176 |
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