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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2019-08-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332219315124
id doaj-6d6c317a080b4fa8a0d0235e5383c97a
record_format Article
collection DOAJ
language English
format Article
sources 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 AT mabozoukpemissi nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT kwashieeklugadegbeku nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT veereshpveerapur nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT mihainegru nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT mariantaulescu nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT vivekchandramohan nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT jagadheshanhiriyan nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT siddalingeshmbanakar nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT thimmaiahnv nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT doddamavatturshivalingaiahsuhas nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT tumbadiadinarayanashettypuneeth nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT sachidanandavijayakumar nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT kossimetowogo nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
AT kodjoaklikokou nephroprotectiveactivityofcombretummicranthumgdonincisplatininducednephrotoxicityinratsinvitroinvivoandinsilicoexperiments
_version_ 1721435333915049984
spelling 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