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
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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.
AbstractList	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. 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 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.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. 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
Audience	Academic
Author	Abd-Elsalam, Sherief Sarhan, Naglaa I. Elkaliny, Heba H. Rizk, Fatma H. Badawi, Rehab El Saadany, Amira A. Dawood, Lamees
AuthorAffiliation	2 Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt 3 Department of Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt 1 Department of Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt 4 Department of histology, Faculty of Medicine, Tanta University, Tanta, Egypt 5 Department of Tropical, Faculty of Medicine, Tanta University, Tanta, Egypt, sherif_tropical@yahoo.com
AuthorAffiliation_xml	– name: 1 Department of Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt – name: 4 Department of histology, Faculty of Medicine, Tanta University, Tanta, Egypt – name: 5 Department of Tropical, Faculty of Medicine, Tanta University, Tanta, Egypt, sherif_tropical@yahoo.com – name: 3 Department of Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt – name: 2 Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt
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Snippet	Methotrexate (MTX) is a drug used in treatment of various malignancies. Unfortunately, it leads to life-threatening complications including hepatorenal... 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...
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SubjectTerms	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
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Title	Metformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone
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Volume	11
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