Sub-Chronic Administration of Vincristine Sulfate Induces Renal Damage and Apoptosis in Rats via Induction of Oxidative Stress and Activation of Raf1-MEK1/2-Erk1/2 Signal Transduction

SUMMARY: In spite of being one of the most powerful anti-cancer drug, the nephrotoxicity of Vincristine (VCR) is not well established in either animals or humans. Hence, this study evaluates the nephrotoxic effect of VCR in rats after sub-chronic long-term administration. Rats were divided into 2 gr...

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Autor principal:	Shati,Ali A
Lenguaje:	English
Publicado:	Sociedad Chilena de Anatomía 2019
Materias:	Vincristine Nephrotoxicity Oxidative stress Apoptosis Rats
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022019000100273
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spelling	oai:scielo:S0717-950220190001002732019-09-11Sub-Chronic Administration of Vincristine Sulfate Induces Renal Damage and Apoptosis in Rats via Induction of Oxidative Stress and Activation of Raf1-MEK1/2-Erk1/2 Signal TransductionShati,Ali A Vincristine Nephrotoxicity Oxidative stress Apoptosis Rats SUMMARY: In spite of being one of the most powerful anti-cancer drug, the nephrotoxicity of Vincristine (VCR) is not well established in either animals or humans. Hence, this study evaluates the nephrotoxic effect of VCR in rats after sub-chronic long-term administration. Rats were divided into 2 groups (n=10/group) of either control and VCR treated rats (50 mg/kg). Treatments were carried out for 30 consecutive days, after which a series of biochemical and molecular experiments related to kidney function were evaluated. VCR administration significantly decreased the survival rate (69.8 %) and impaired renal function as evidenced by lowered creatinine (Cr) clearance (Ccr), high serum levels of urea and Cr, increased urinary protein levels and resulted in sever cortex pathological alterations, including glomerulus congestion and damage as well as vascular degenerations up to necrosis of both proximal and distal convoluted tubules. Mechanistically, VCR lowered renal antioxidant potential and ATP levels, enhanced lipid peroxidation and induced inflammation. In addition, VCR induced activation of Raf-1-MEK1/2-ERK1/2 signaling pathway leading to downregulation of Bcl2 and upregulation of P53, Bax, and cleaved caspase-3. In conclusion, these findings show a nephrotoxic effect of VCR sulfate in rats after sub-chronic administration and such effect was mediated by activation of ERK1/2 induced apoptosis.info:eu-repo/semantics/openAccessSociedad Chilena de AnatomíaInternational Journal of Morphology v.37 n.1 20192019-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022019000100273en10.4067/S0717-95022019000100273
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Vincristine Nephrotoxicity Oxidative stress Apoptosis Rats
spellingShingle	Vincristine Nephrotoxicity Oxidative stress Apoptosis Rats Shati,Ali A Sub-Chronic Administration of Vincristine Sulfate Induces Renal Damage and Apoptosis in Rats via Induction of Oxidative Stress and Activation of Raf1-MEK1/2-Erk1/2 Signal Transduction
description	SUMMARY: In spite of being one of the most powerful anti-cancer drug, the nephrotoxicity of Vincristine (VCR) is not well established in either animals or humans. Hence, this study evaluates the nephrotoxic effect of VCR in rats after sub-chronic long-term administration. Rats were divided into 2 groups (n=10/group) of either control and VCR treated rats (50 mg/kg). Treatments were carried out for 30 consecutive days, after which a series of biochemical and molecular experiments related to kidney function were evaluated. VCR administration significantly decreased the survival rate (69.8 %) and impaired renal function as evidenced by lowered creatinine (Cr) clearance (Ccr), high serum levels of urea and Cr, increased urinary protein levels and resulted in sever cortex pathological alterations, including glomerulus congestion and damage as well as vascular degenerations up to necrosis of both proximal and distal convoluted tubules. Mechanistically, VCR lowered renal antioxidant potential and ATP levels, enhanced lipid peroxidation and induced inflammation. In addition, VCR induced activation of Raf-1-MEK1/2-ERK1/2 signaling pathway leading to downregulation of Bcl2 and upregulation of P53, Bax, and cleaved caspase-3. In conclusion, these findings show a nephrotoxic effect of VCR sulfate in rats after sub-chronic administration and such effect was mediated by activation of ERK1/2 induced apoptosis.
author	Shati,Ali A
author_facet	Shati,Ali A
author_sort	Shati,Ali A
title	Sub-Chronic Administration of Vincristine Sulfate Induces Renal Damage and Apoptosis in Rats via Induction of Oxidative Stress and Activation of Raf1-MEK1/2-Erk1/2 Signal Transduction
title_short	Sub-Chronic Administration of Vincristine Sulfate Induces Renal Damage and Apoptosis in Rats via Induction of Oxidative Stress and Activation of Raf1-MEK1/2-Erk1/2 Signal Transduction
title_full	Sub-Chronic Administration of Vincristine Sulfate Induces Renal Damage and Apoptosis in Rats via Induction of Oxidative Stress and Activation of Raf1-MEK1/2-Erk1/2 Signal Transduction
title_fullStr	Sub-Chronic Administration of Vincristine Sulfate Induces Renal Damage and Apoptosis in Rats via Induction of Oxidative Stress and Activation of Raf1-MEK1/2-Erk1/2 Signal Transduction
title_full_unstemmed	Sub-Chronic Administration of Vincristine Sulfate Induces Renal Damage and Apoptosis in Rats via Induction of Oxidative Stress and Activation of Raf1-MEK1/2-Erk1/2 Signal Transduction
title_sort	sub-chronic administration of vincristine sulfate induces renal damage and apoptosis in rats via induction of oxidative stress and activation of raf1-mek1/2-erk1/2 signal transduction
publisher	Sociedad Chilena de Anatomía
publishDate	2019
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022019000100273
work_keys_str_mv	AT shatialia subchronicadministrationofvincristinesulfateinducesrenaldamageandapoptosisinratsviainductionofoxidativestressandactivationofraf1mek12erk12signaltransduction
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Sub-Chronic Administration of Vincristine Sulfate Induces Renal Damage and Apoptosis in Rats via Induction of Oxidative Stress and Activation of Raf1-MEK1/2-Erk1/2 Signal Transduction

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