Back to Journals » Journal of Inflammation Research » Volume 11

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

Authors Rizk FH, El Saadany AA, Dawood L, Elkaliny HH, Sarhan NI, Badawi R, Abd-Elsalam S

Received 30 June 2018

Accepted for publication 17 September 2018

Published 8 November 2018 Volume 2018:11 Pages 421—429

DOI https://doi.org/10.2147/JIR.S178767

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 4

Editor who approved publication: Dr Ning Quan


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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]