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

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...

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Published in:Journal of inflammation research Vol. 11; pp. 421 - 429
Main Authors: Rizk, Fatma H., El Saadany, Amira A., Dawood, Lamees, Elkaliny, Heba H., Sarhan, Naglaa I., Badawi, Rehab, Abd-Elsalam, Sherief
Format: Journal Article
Language:English
Published: New Zealand Dove Medical Press Limited 01.01.2018
Taylor & Francis Ltd
Dove Medical Press
Subjects:
Antidiabetics
Antineoplastic agents
Antioxidants
Antioxidants (Nutrients)
Apoptosis
Arthritis
ATPases
B cells
Biochemistry
Cancer therapies
Cancer treatment
Chemotherapy
Complications and side effects
COX-2 inhibitors
Cytotoxicity
Drug dosages
EDTA
Enzymes
Experiments
Hepatorenal toxicity
Immunomodulators
Kidneys
Kinases
Laboratory animals
Liver
Medical research
Medicine
Messenger RNA
Metformin
Methotrexate
Mitochondria
Original Research
Oxidative stress
Proteins
RNA
Toxicity
Type 2 diabetes
United States > US
Egypt
hepatorenal toxicity
metformin
methotrexate
ISSN:1178-7031, 1178-7031
Online Access:Get full text
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Summary: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.
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ISSN:1178-7031
1178-7031
DOI:10.2147/JIR.S178767