Metformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone

Fatma H Rizk,1 Amira A El Saadany,2 Lamees Dawood,3 Heba H Elkaliny,4 Naglaa I Sarhan,4 Rehab Badawi,5 Sherief Abd-Elsalam5 1Department of Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt; 2Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt; 3Department of...

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Autores principales:	Rizk FH, El Saadany AA, Dawood L, Elkaliny HH, Sarhan NI, Badawi R, Abd-Elsalam S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Hepatorenal toxicity Metformin Methotrexate Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/8aad0c6654cf44f8ace7ae9454e1fdcc
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spelling	oai:doaj.org-article:8aad0c6654cf44f8ace7ae9454e1fdcc2021-12-02T02:59:20ZMetformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone1178-7031https://doaj.org/article/8aad0c6654cf44f8ace7ae9454e1fdcc2018-11-01T00:00:00Zhttps://www.dovepress.com/metformin-ameliorated-methotrexate-induced-hepatorenal-toxicity-in-rat-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Fatma H Rizk,1 Amira A El Saadany,2 Lamees Dawood,3 Heba H Elkaliny,4 Naglaa I Sarhan,4 Rehab Badawi,5 Sherief Abd-Elsalam5 1Department of Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt; 2Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt; 3Department of Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt; 4Department of Histology, Faculty of Medicine, Tanta University, Tanta, Egypt; 5Department of Tropical, Faculty of Medicine, Tanta University, Tanta, Egypt Abstract: Methotrexate (MTX) is a drug used in treatment of various malignancies. Unfortunately, it leads to life-threatening complications including hepatorenal toxicity. Previous studies revealed the protective effects of metformin (MET) on hepatorenal toxicity in other models in addition to its anticancer effects. The current study investigates the effect of MET on MTX-induced hepatorenal toxicity and the possible mechanisms involved in this toxicity which can be overwhelmed by MET. Thirty male rats were divided into 3 groups: normal control, MTX treated and MET/MTX treated. After 7 days, MTX induced hepatorenal toxicity as proved by histological examinations and biochemical analysis of liver and kidney functions. Also, it led to significant increase in hepatic and renal malondialdehyde levels, significant decrease in hepatic and renal total antioxidant capacity levels and Na+/K+-ATPase activities and significant up regulation of mRNA expressions of nuclear factor kappa-light-chain-enhancer of activated B cells, cyclooxygenase-2 and caspase 3 compared with the control group. While, MET could significantly reduce hepatorenal toxicity and counteract the effects of MTX on all measured parameters. In conclusion, MET can be an effective adjuvant to MTX chemotherapy that could ameliorate its hepatorenal toxicity through antioxidant, anti-inflammatory and anti-apoptotic mechanisms. Keywords: hepatorenal toxicity, metformin, methotrexateRizk FHEl Saadany AADawood LElkaliny HHSarhan NIBadawi RAbd-Elsalam SDove Medical PressarticleHepatorenal toxicityMetforminMethotrexatePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 11, Pp 421-429 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hepatorenal toxicity Metformin Methotrexate Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	Hepatorenal toxicity Metformin Methotrexate Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Rizk FH El Saadany AA Dawood L Elkaliny HH Sarhan NI Badawi R Abd-Elsalam S Metformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone
description	Fatma H Rizk,1 Amira A El Saadany,2 Lamees Dawood,3 Heba H Elkaliny,4 Naglaa I Sarhan,4 Rehab Badawi,5 Sherief Abd-Elsalam5 1Department of Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt; 2Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt; 3Department of Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt; 4Department of Histology, Faculty of Medicine, Tanta University, Tanta, Egypt; 5Department of Tropical, Faculty of Medicine, Tanta University, Tanta, Egypt Abstract: Methotrexate (MTX) is a drug used in treatment of various malignancies. Unfortunately, it leads to life-threatening complications including hepatorenal toxicity. Previous studies revealed the protective effects of metformin (MET) on hepatorenal toxicity in other models in addition to its anticancer effects. The current study investigates the effect of MET on MTX-induced hepatorenal toxicity and the possible mechanisms involved in this toxicity which can be overwhelmed by MET. Thirty male rats were divided into 3 groups: normal control, MTX treated and MET/MTX treated. After 7 days, MTX induced hepatorenal toxicity as proved by histological examinations and biochemical analysis of liver and kidney functions. Also, it led to significant increase in hepatic and renal malondialdehyde levels, significant decrease in hepatic and renal total antioxidant capacity levels and Na+/K+-ATPase activities and significant up regulation of mRNA expressions of nuclear factor kappa-light-chain-enhancer of activated B cells, cyclooxygenase-2 and caspase 3 compared with the control group. While, MET could significantly reduce hepatorenal toxicity and counteract the effects of MTX on all measured parameters. In conclusion, MET can be an effective adjuvant to MTX chemotherapy that could ameliorate its hepatorenal toxicity through antioxidant, anti-inflammatory and anti-apoptotic mechanisms. Keywords: hepatorenal toxicity, metformin, methotrexate
format	article
author	Rizk FH El Saadany AA Dawood L Elkaliny HH Sarhan NI Badawi R Abd-Elsalam S
author_facet	Rizk FH El Saadany AA Dawood L Elkaliny HH Sarhan NI Badawi R Abd-Elsalam S
author_sort	Rizk FH
title	Metformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone
title_short	Metformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone
title_full	Metformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone
title_fullStr	Metformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone
title_full_unstemmed	Metformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone
title_sort	metformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/8aad0c6654cf44f8ace7ae9454e1fdcc
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Metformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone

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