Tags

Type your tag names separated by a space and hit enter

Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments.
Biomed Pharmacother. 2019 Aug; 116:108961.BP

Abstract

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.

Authors+Show Affiliations

Faculty 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. Electronic address: mabozou@gmail.com.Faculty of Sciences, University of Lomé, Togo.Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India. Electronic address: veeresh36@gmail.com.University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, Romania.University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, Romania.Department of Biotechnology, Siddaganga Institute of Technology, Tumkur, 572103, Karnataka, India.Anthem Biosciences Pvt. Ltd., Industrial Area Phase I, Bommasandra, Hosur Road, Bangalore, 560099, India.Anthem Biosciences Pvt. Ltd., Industrial Area Phase I, Bommasandra, Hosur Road, Bangalore, 560099, India.Anthem Biosciences Pvt. Ltd., Industrial Area Phase I, Bommasandra, Hosur Road, Bangalore, 560099, India.Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India.Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India.Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India.Faculty of Sciences, University of Lomé, Togo.Faculty of Sciences, University of Lomé, Togo.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31146106

Citation

Kpemissi, Mabozou, et al. "Nephroprotective Activity of Combretum Micranthum G. Don in Cisplatin Induced Nephrotoxicity in Rats: In-vitro, In-vivo and In-silico Experiments." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 116, 2019, p. 108961.
Kpemissi M, Eklu-Gadegbeku K, Veerapur VP, et al. Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments. Biomed Pharmacother. 2019;116:108961.
Kpemissi, M., Eklu-Gadegbeku, K., Veerapur, V. P., Negru, M., Taulescu, M., Chandramohan, V., Hiriyan, J., Banakar, S. M., Nv, T., Suhas, D. S., Puneeth, T. A., Vijayakumar, S., Metowogo, K., & Aklikokou, K. (2019). Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 116, 108961. https://doi.org/10.1016/j.biopha.2019.108961
Kpemissi M, et al. Nephroprotective Activity of Combretum Micranthum G. Don in Cisplatin Induced Nephrotoxicity in Rats: In-vitro, In-vivo and In-silico Experiments. Biomed Pharmacother. 2019;116:108961. PubMed PMID: 31146106.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments. AU - Kpemissi,Mabozou, AU - Eklu-Gadegbeku,Kwashie, AU - Veerapur,Veeresh P, AU - Negru,Mihai, AU - Taulescu,Marian, AU - Chandramohan,Vivek, AU - Hiriyan,Jagadheshan, AU - Banakar,Siddalingesh M, AU - Nv,Thimmaiah, AU - Suhas,Doddamavattur Shivalingaiah, AU - Puneeth,Tumbadi Adinarayanashetty, AU - Vijayakumar,Sachidananda, AU - Metowogo,Kossi, AU - Aklikokou,Kodjo, Y1 - 2019/05/28/ PY - 2019/04/04/received PY - 2019/05/02/revised PY - 2019/05/08/accepted PY - 2019/5/31/pubmed PY - 2020/1/7/medline PY - 2019/5/31/entrez KW - HEK-293 KW - Kidney KW - Molecular docking KW - Molecular dynamic studies KW - Nephrotoxicity KW - Oxidative stress SP - 108961 EP - 108961 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 116 N2 - 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. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/31146106/Nephroprotective_activity_of_Combretum_micranthum_G__Don_in_cisplatin_induced_nephrotoxicity_in_rats:_In_vitro_in_vivo_and_in_silico_experiments_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(19)31512-4 DB - PRIME DP - Unbound Medicine ER -