Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments
Nephrotoxicity is known to be a major complication during cisplatin chemotherapy in cancer patients. In the present study, the protective effect of a hydroalcoholic extract of Combretum micranthum (CM) against cisplatin (CP)-induced renal damage was evaluated using in-vitro human embryonic kidney (H...
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Elsevier
2019-08-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332219315124 |
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English |
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Article |
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DOAJ |
author |
Mabozou Kpemissi Kwashie Eklu-Gadegbeku Veeresh P. Veerapur Mihai Negru Marian Taulescu Vivek Chandramohan Jagadheshan Hiriyan Siddalingesh M. Banakar Thimmaiah NV Doddamavattur Shivalingaiah Suhas Tumbadi Adinarayanashetty Puneeth Sachidananda Vijayakumar Kossi Metowogo Kodjo Aklikokou |
spellingShingle |
Mabozou Kpemissi Kwashie Eklu-Gadegbeku Veeresh P. Veerapur Mihai Negru Marian Taulescu Vivek Chandramohan Jagadheshan Hiriyan Siddalingesh M. Banakar Thimmaiah NV Doddamavattur Shivalingaiah Suhas Tumbadi Adinarayanashetty Puneeth Sachidananda Vijayakumar Kossi Metowogo Kodjo Aklikokou Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments Biomedicine & Pharmacotherapy Kidney Nephrotoxicity HEK-293 Oxidative stress Molecular docking Molecular dynamic studies |
author_facet |
Mabozou Kpemissi Kwashie Eklu-Gadegbeku Veeresh P. Veerapur Mihai Negru Marian Taulescu Vivek Chandramohan Jagadheshan Hiriyan Siddalingesh M. Banakar Thimmaiah NV Doddamavattur Shivalingaiah Suhas Tumbadi Adinarayanashetty Puneeth Sachidananda Vijayakumar Kossi Metowogo Kodjo Aklikokou |
author_sort |
Mabozou Kpemissi |
title |
Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments |
title_short |
Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments |
title_full |
Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments |
title_fullStr |
Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments |
title_full_unstemmed |
Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments |
title_sort |
nephroprotective activity of combretum micranthum g. don in cisplatin induced nephrotoxicity in rats: in-vitro, in-vivo and in-silico experiments |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2019-08-01 |
description |
Nephrotoxicity is known to be a major complication during cisplatin chemotherapy in cancer patients. In the present study, the protective effect of a hydroalcoholic extract of Combretum micranthum (CM) against cisplatin (CP)-induced renal damage was evaluated using in-vitro human embryonic kidney (HEK)-293 cells and in-vivo experiments. Further, in-silico molecular docking and dynamic experiments were carried out with bioactive compounds of the title plant against nuclear factor kappa B (NF-κB) and soluble epoxide hydrolase (sEH). Incubation of HEK-293 cells with cisplatin resulted in a significant increase in cell death with changes in normal cellular morphology. Co-treatment of HEK-293 cells with CP and CM extract at varying concentrations resulted in significant enhancement of cell growth compared to CP treatment indicating the cytoprotective activity of CM with an EC50 8.136 μg/mL. In vivo nephroprotective activity was evaluated by administering CM (200 and 400 mg/kg, p.o) to rats for 10 days followed by single intraperitonial injection of CP (7.5 mg/kg) on the 5th day of the experiment. Nephrotoxicity induced by CP was apparent by elevated levels of serum and urine kidney function markers, transaminases, oxidative stress markers and histopathological alterations in kidney. Pre-treatment with CM normalized the renal function at both the doses by ameliorating the CP-induced renal damage markers, oxidative stress and histopathological variations. In-silico studies showed that, out of the thirty bioactive compounds, isovitexin and gallic acid exhibited a higher docking score of −22.467, −21.167 kcal/mol against NF-κB. Cianidanol and epicatechin exhibited a higher docking score of −14.234, −14.209 kcal/mol against sEH. The protective effect of CM extract in CP-induced nephrotoxicity might be attributed to its antioxidant, anti-inflammatory activity by inhibiting NF-κB and sEH upregulation. |
topic |
Kidney Nephrotoxicity HEK-293 Oxidative stress Molecular docking Molecular dynamic studies |
url |
http://www.sciencedirect.com/science/article/pii/S0753332219315124 |
work_keys_str_mv |
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doaj-6d6c317a080b4fa8a0d0235e5383c97a2021-05-20T07:38:16ZengElsevierBiomedicine & Pharmacotherapy0753-33222019-08-01116108961Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experimentsMabozou Kpemissi0Kwashie Eklu-Gadegbeku1Veeresh P. Veerapur2Mihai Negru3Marian Taulescu4Vivek Chandramohan5Jagadheshan Hiriyan6Siddalingesh M. Banakar7Thimmaiah NV8Doddamavattur Shivalingaiah Suhas9Tumbadi Adinarayanashetty Puneeth10Sachidananda Vijayakumar11Kossi Metowogo12Kodjo Aklikokou13Faculty of Sciences, University of Lomé, Togo; University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, Romania; Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India; Corresponding authors at: Laboratory of Physiology/Pharmacology, Department of Animal Physiology, Faculty of Sciences, University of Lomé, Togo.Faculty of Sciences, University of Lomé, TogoSree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India; Corresponding author.University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, RomaniaUniversity of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, RomaniaDepartment of Biotechnology, Siddaganga Institute of Technology, Tumkur, 572103, Karnataka, IndiaAnthem Biosciences Pvt. Ltd., Industrial Area Phase I, Bommasandra, Hosur Road, Bangalore, 560099, IndiaAnthem Biosciences Pvt. Ltd., Industrial Area Phase I, Bommasandra, Hosur Road, Bangalore, 560099, IndiaAnthem Biosciences Pvt. Ltd., Industrial Area Phase I, Bommasandra, Hosur Road, Bangalore, 560099, IndiaSree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, IndiaSree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, IndiaSree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, IndiaFaculty of Sciences, University of Lomé, TogoFaculty of Sciences, University of Lomé, TogoNephrotoxicity is known to be a major complication during cisplatin chemotherapy in cancer patients. In the present study, the protective effect of a hydroalcoholic extract of Combretum micranthum (CM) against cisplatin (CP)-induced renal damage was evaluated using in-vitro human embryonic kidney (HEK)-293 cells and in-vivo experiments. Further, in-silico molecular docking and dynamic experiments were carried out with bioactive compounds of the title plant against nuclear factor kappa B (NF-κB) and soluble epoxide hydrolase (sEH). Incubation of HEK-293 cells with cisplatin resulted in a significant increase in cell death with changes in normal cellular morphology. Co-treatment of HEK-293 cells with CP and CM extract at varying concentrations resulted in significant enhancement of cell growth compared to CP treatment indicating the cytoprotective activity of CM with an EC50 8.136 μg/mL. In vivo nephroprotective activity was evaluated by administering CM (200 and 400 mg/kg, p.o) to rats for 10 days followed by single intraperitonial injection of CP (7.5 mg/kg) on the 5th day of the experiment. Nephrotoxicity induced by CP was apparent by elevated levels of serum and urine kidney function markers, transaminases, oxidative stress markers and histopathological alterations in kidney. Pre-treatment with CM normalized the renal function at both the doses by ameliorating the CP-induced renal damage markers, oxidative stress and histopathological variations. In-silico studies showed that, out of the thirty bioactive compounds, isovitexin and gallic acid exhibited a higher docking score of −22.467, −21.167 kcal/mol against NF-κB. Cianidanol and epicatechin exhibited a higher docking score of −14.234, −14.209 kcal/mol against sEH. The protective effect of CM extract in CP-induced nephrotoxicity might be attributed to its antioxidant, anti-inflammatory activity by inhibiting NF-κB and sEH upregulation.http://www.sciencedirect.com/science/article/pii/S0753332219315124KidneyNephrotoxicityHEK-293Oxidative stressMolecular dockingMolecular dynamic studies |