PMID- 31146106 OWN - NLM STAT- MEDLINE DCOM- 20200106 LR - 20200106 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 116 DP - 2019 Aug TI - Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments. PG - 108961 LID - S0753-3322(19)31512-4 [pii] LID - 10.1016/j.biopha.2019.108961 [doi] AB - 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-kappaB) 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 EC(50) 8.136 mug/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-kappaB. 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-in fl ammatory activity by inhibiting NF-kappaB and sEH upregulation. CI - Copyright (c) 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Kpemissi, Mabozou AU - Kpemissi M AD - Faculty of Sciences, University of Lome, 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. Electronic address: mabozou@gmail.com. FAU - Eklu-Gadegbeku, Kwashie AU - Eklu-Gadegbeku K AD - Faculty of Sciences, University of Lome, Togo. FAU - Veerapur, Veeresh P AU - Veerapur VP AD - Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India. Electronic address: veeresh36@gmail.com. FAU - Negru, Mihai AU - Negru M AD - University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, Romania. FAU - Taulescu, Marian AU - Taulescu M AD - University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, Romania. FAU - Chandramohan, Vivek AU - Chandramohan V AD - Department of Biotechnology, Siddaganga Institute of Technology, Tumkur, 572103, Karnataka, India. FAU - Hiriyan, Jagadheshan AU - Hiriyan J AD - Anthem Biosciences Pvt. Ltd., Industrial Area Phase I, Bommasandra, Hosur Road, Bangalore, 560099, India. FAU - Banakar, Siddalingesh M AU - Banakar SM AD - Anthem Biosciences Pvt. Ltd., Industrial Area Phase I, Bommasandra, Hosur Road, Bangalore, 560099, India. FAU - Nv, Thimmaiah AU - Nv T AD - Anthem Biosciences Pvt. Ltd., Industrial Area Phase I, Bommasandra, Hosur Road, Bangalore, 560099, India. FAU - Suhas, Doddamavattur Shivalingaiah AU - Suhas DS AD - Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India. FAU - Puneeth, Tumbadi Adinarayanashetty AU - Puneeth TA AD - Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India. FAU - Vijayakumar, Sachidananda AU - Vijayakumar S AD - Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India. FAU - Metowogo, Kossi AU - Metowogo K AD - Faculty of Sciences, University of Lome, Togo. FAU - Aklikokou, Kodjo AU - Aklikokou K AD - Faculty of Sciences, University of Lome, Togo. LA - eng PT - Journal Article DEP - 20190528 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Biomarkers) RN - 0 (Plant Extracts) RN - 0 (Protective Agents) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Animals MH - Biomarkers/blood/urine MH - Body Weight/drug effects MH - Cisplatin/*adverse effects MH - Combretum/*chemistry MH - *Computer Simulation MH - HEK293 Cells MH - Humans MH - Kidney/drug effects/*pathology MH - Male MH - Molecular Docking Simulation MH - Molecular Dynamics Simulation MH - Oxidative Stress/drug effects MH - Plant Extracts/pharmacology MH - Protective Agents/*pharmacology MH - Rats, Wistar OTO - NOTNLM OT - HEK-293 OT - Kidney OT - Molecular docking OT - Molecular dynamic studies OT - Nephrotoxicity OT - Oxidative stress EDAT- 2019/05/31 06:00 MHDA- 2020/01/07 06:00 CRDT- 2019/05/31 06:00 PHST- 2019/04/04 00:00 [received] PHST- 2019/05/02 00:00 [revised] PHST- 2019/05/08 00:00 [accepted] PHST- 2019/05/31 06:00 [pubmed] PHST- 2020/01/07 06:00 [medline] PHST- 2019/05/31 06:00 [entrez] AID - S0753-3322(19)31512-4 [pii] AID - 10.1016/j.biopha.2019.108961 [doi] PST - ppublish SO - Biomed Pharmacother. 2019 Aug;116:108961. doi: 10.1016/j.biopha.2019.108961. Epub 2019 May 28.