Small-Dose Sunitinib Modulates p53, Bcl-2, STAT3, and ERK1/2 Pathways and Protects against Adenine-Induced Nephrotoxicity

Pharmaceuticals
Mohamed A SalehNashwa M Abu-Elsaad

Abstract

The therapeutic use of numerous pharmacological agents may be limited due to their nephrotoxicity and associated kidney injury. The aim of our study is to test the hypothesis that the blockade of tyrosine kinase-linked receptors signaling protects against chemically induced nephrotoxicity. To test our hypothesis, we investigated sunitinib as an inhibitor for tyrosine kinase signaling for both vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptors (PDGFR) against adenine-induced nephrotoxicity. Four groups of adult male Swiss albino mice were investigated: normal group, adenine group, sunitinib group, and the adenine+sunitinib group that received concurrent administration for both adenine and sunitinib. Kidney function and oxidative stress biomarkers were analyzed. Tubular injury and histopathological changes were examined. Renal expression of B-cell lymphoma-2 (Bcl-2), the tumor suppressor p53, transforming growth factor beta-1 (TGF-β1), phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2), and phospho-signal transducer and activator of transcription (phospho-STAT3) were measured. The results obtained showed significant improvement (p < 0.05) in kidney function and antioxidant b...Continue Reading

References

Jun 1, 1979·Analytical Biochemistry·H OhkawaK Yagi
Jun 13, 2000·Oncogene·T BowmanR Jove
Mar 23, 2001·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·A S Woolf, H T Yuan
Apr 23, 2003·Journal of the American Society of Nephrology : JASN·Frank EitnerUNKNOWN ERCB-Consortium
Jan 20, 2007·Science·Michelangelo CordenonsiStefano Piccolo
Jun 8, 2007·Journal of the American Society of Nephrology : JASN·Enqi LiuJianglin Fan
Jun 10, 2008·International Journal of Clinical Pharmacology and Therapeutics·T HawthorneY-D Halvorsen
Jul 26, 2008·Reviews in Endocrine & Metabolic Disorders·B S KasinathD Feliers
Nov 8, 2008·Current Diabetes Reports·Sheldon Chen, Fuad N Ziyadeh
Oct 31, 2009·Journal of the American Society of Nephrology : JASN·Wilfred Lieberthal, Jerrold S Levine
Nov 7, 2009·Journal of the American Society of Nephrology : JASN·Li ZhouHui Y Lan
Jul 16, 2010·Experimental & Molecular Medicine·Eun-Hee NamPyeung-Hyeun Kim
Mar 2, 2011·International Journal of Experimental Pathology·Soma Meran, Robert Steadman
Oct 20, 2011·Nature Reviews. Nephrology·Youhua Liu
Jun 26, 2012·Biochimica Et Biophysica Acta·Christian Beyer, Jörg H W Distler
Jan 18, 2013·Kidney International·Jinhua TangShougang Zhuang
Mar 6, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chao LiJohn F Kuemmerle
May 11, 2016·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Abderrahim NemmarBadreldin H Ali
Feb 28, 2017·Scientific Reports·Ruhao YangDongshan Zhang
Nov 18, 2017·Cell Death and Differentiation·Brandon J AubreyAndreas Strasser
Aug 6, 2019·FEBS Letters·Fang-Fang HeYu-Mei Wang
Nov 19, 2019·American Journal of Physiology. Renal Physiology·Emilia BigaevaMiriam Boersema
Jan 1, 2018·Cell Death and Differentiation·Brandon J AubreyAndreas Strasser

❮ Previous
Next ❯

Citations

Apr 23, 2021·Human & Experimental Toxicology·A M Kabel, S A Salama

❮ Previous
Next ❯

Methods Mentioned

BETA
MDA

Software Mentioned

GraphPad
GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.