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Potential protective effect of etanercept and aminoguanidine in methotrexate-induced hepatotoxicity and nephrotoxicity in rats.
Eur J Pharmacol. 2015 Dec 05; 768:1-12.EJ

Abstract

Methotrexate (MTX), a chemotherapeutic and immunosuppressant drug, is generally well-tolerated by most patients. However, its cytotoxic nature contributes to life-threatening side effects including hepatotoxicity and nephrotoxicity. The present study investigated the possible role of tumor necrosis factor-alpha (TNF-α) inhibitor, etanercept and inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine, on MTX-induced hepatotoxicity and nephrotoxicity in rats. Rats were divided into 7 groups: control group, etanercept group, aminoguanidine group, MTX group, MTX+etanercept group, MTX+aminoguanidine group, and MTX+etanercept+aminoguanidine group. MTX caused hepatotoxicity and nephrotoxicity as evidenced biochemically by significant increase in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and creatinine, respectively as well as by histopathological changes. Such effects were associated with significant changes in oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase, and glutathione (GSH)) as well as by upregulation of TNF-α, iNOS and caspase-3 expressions in hepatic and renal tissues. Etanercept and aminoguanidine significantly attenuated MTX-hepatotoxicity and nephrotoxicity. The protective effect of either agent was associated with significant improvement in oxidative stress parameters as well as by downregulation of TNF-α, iNOS and caspase-3 expressions in hepatic and renal tissues. The study suggested that inhibitors of either TNF-α and/or iNOS have protective effect in MTX-induced hepatotoxicity and nephrotoxicity. The protective effect of either agent relies, at least partially, on their antioxidant effects and decreased TNF-α, iNOS, and caspase-3 expressions.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.Department of Pharmacology, Faculty of Medicine, Minia University, Egypt. Electronic address: maim69@yahoo.com.Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.Department of Pathology, Faculty of Medicine, Minia University, Egypt.Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26332135

Citation

Hafez, Heba M., et al. "Potential Protective Effect of Etanercept and Aminoguanidine in Methotrexate-induced Hepatotoxicity and Nephrotoxicity in Rats." European Journal of Pharmacology, vol. 768, 2015, pp. 1-12.
Hafez HM, Ibrahim MA, Ibrahim SA, et al. Potential protective effect of etanercept and aminoguanidine in methotrexate-induced hepatotoxicity and nephrotoxicity in rats. Eur J Pharmacol. 2015;768:1-12.
Hafez, H. M., Ibrahim, M. A., Ibrahim, S. A., Amin, E. F., Goma, W., & Abdelrahman, A. M. (2015). Potential protective effect of etanercept and aminoguanidine in methotrexate-induced hepatotoxicity and nephrotoxicity in rats. European Journal of Pharmacology, 768, 1-12. https://doi.org/10.1016/j.ejphar.2015.08.047
Hafez HM, et al. Potential Protective Effect of Etanercept and Aminoguanidine in Methotrexate-induced Hepatotoxicity and Nephrotoxicity in Rats. Eur J Pharmacol. 2015 Dec 5;768:1-12. PubMed PMID: 26332135.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential protective effect of etanercept and aminoguanidine in methotrexate-induced hepatotoxicity and nephrotoxicity in rats. AU - Hafez,Heba M, AU - Ibrahim,Mohamed A, AU - Ibrahim,Salwa A, AU - Amin,Entesar F, AU - Goma,Wafaey, AU - Abdelrahman,Aly M, Y1 - 2015/08/30/ PY - 2015/06/28/received PY - 2015/08/24/revised PY - 2015/08/26/accepted PY - 2015/9/3/entrez PY - 2015/9/4/pubmed PY - 2016/9/14/medline KW - Aminoguanidine KW - Etanercept KW - Hepatotoxicity KW - Methotrexate KW - Nephrotoxicity SP - 1 EP - 12 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 768 N2 - Methotrexate (MTX), a chemotherapeutic and immunosuppressant drug, is generally well-tolerated by most patients. However, its cytotoxic nature contributes to life-threatening side effects including hepatotoxicity and nephrotoxicity. The present study investigated the possible role of tumor necrosis factor-alpha (TNF-α) inhibitor, etanercept and inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine, on MTX-induced hepatotoxicity and nephrotoxicity in rats. Rats were divided into 7 groups: control group, etanercept group, aminoguanidine group, MTX group, MTX+etanercept group, MTX+aminoguanidine group, and MTX+etanercept+aminoguanidine group. MTX caused hepatotoxicity and nephrotoxicity as evidenced biochemically by significant increase in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and creatinine, respectively as well as by histopathological changes. Such effects were associated with significant changes in oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase, and glutathione (GSH)) as well as by upregulation of TNF-α, iNOS and caspase-3 expressions in hepatic and renal tissues. Etanercept and aminoguanidine significantly attenuated MTX-hepatotoxicity and nephrotoxicity. The protective effect of either agent was associated with significant improvement in oxidative stress parameters as well as by downregulation of TNF-α, iNOS and caspase-3 expressions in hepatic and renal tissues. The study suggested that inhibitors of either TNF-α and/or iNOS have protective effect in MTX-induced hepatotoxicity and nephrotoxicity. The protective effect of either agent relies, at least partially, on their antioxidant effects and decreased TNF-α, iNOS, and caspase-3 expressions. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/26332135/Potential_protective_effect_of_etanercept_and_aminoguanidine_in_methotrexate_induced_hepatotoxicity_and_nephrotoxicity_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(15)30222-3 DB - PRIME DP - Unbound Medicine ER -