CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues

Frontiers in Pharmacology
Sarah A Abd El-AalHanan S El-Abhar

Abstract

Statins were reported to lower the Coenzyme Q10 (CoQ10) content upon their inhibition of HMG-CoA reductase enzyme and both are known to possess neuroprotective potentials; therefore, the aim is to assess the possible use of CoQ10 as an adds-on therapy to rosuvastatin to improve its effect using global I/R model. Rats were allocated into sham, I/R, rosuvastatin (10 mg/kg), CoQ10 (10 mg/kg) and their combination. Drugs were administered orally for 7 days before I/R. Pretreatment with rosuvastatin and/or CoQ10 inhibited the hippocampal content of malondialdehyde, nitric oxide, and boosted glutathione and superoxide dismutase. They also opposed the upregulation of gp91(phox), and p47(phox) subunits of NADPH oxidase. Meanwhile, both agents reduced content/expression of TNF-α, iNOS, NF-κBp65, ICAM-1, and MPO. Besides, all regimens abated cytochrome c, caspase-3 and Bax, but increased Bcl-2 in favor of cell survival. On the molecular level, they increased p-Akt and its downstream target p-FOXO3A, with the inhibition of the nuclear content of FOXO3A to downregulate the expression of Bim, a pro-apoptotic gene. Additionally, both treatments downregulate the JNK3/c-Jun signaling pathway. The effect of the combination regimen overrides tha...Continue Reading

References

Mar 3, 2004·Archives of Biochemistry and Biophysics·Andrew M JamesMichael P Murphy
Feb 18, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yanqin GaoJun Chen
May 14, 2005·Free Radical Biology & Medicine·Peter J Crack, Juliet M Taylor
Mar 16, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hidenori EndoPak H Chan
Jul 28, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hidenori EndoPak H Chan
Dec 29, 2007·Stroke; a Journal of Cerebral Circulation·Vincent PrinzMatthias Endres
Jul 31, 2008·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Keita MayanagiDavid W Busija
Apr 8, 2009·Nature Neuroscience·Takahiro MiyawakiR Suzanne Zukin
May 19, 2009·International Journal of Pharmaceutics·Prabagar BalakrishnanHan-Gon Choi
Jul 23, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Deyuan LiDezhi Mu
Jan 7, 2010·Journal of Neurochemistry·Chao LiuJianguo Chen
Feb 5, 2010·Journal of Leukocyte Biology·Rong JinGuohong Li
Jan 1, 2009·Advances in Experimental Medicine and Biology·Kohji Fukunaga, Norifumi Shioda
Aug 18, 2010·International Journal of Radiation Biology·Amal A Abd-El-FattahMona A El-Ghazaly
Sep 14, 2010·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Yu-Chang HouYuh-Chiang Shen
Oct 1, 2010·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Midori A YenariRaymond A Swanson
Jan 26, 2011·European Journal of Pharmacology·Amr A FouadMohamed T Yacoubi
Jul 19, 2011·Neuroscience Letters·Sarah B MartinElizabeth Head
Dec 17, 2011·Free Radical Biology & Medicine·Karly C SourrisJosephine M Forbes
Jan 10, 2012·Environmental Toxicology and Pharmacology·Amr A Fouad, Iyad Jresat
Jan 26, 2012·The Journal of Biological Chemistry·Suryakant K Niture, Anil K Jaiswal
Jun 20, 2012·Neurochemistry International·Fabrício SimãoChristianne G Salbego
Jan 10, 2013·Drug and Chemical Toxicology·Sarah A Abd El-AalSanaa A Kenawy

❮ Previous
Next ❯

Citations

Mar 10, 2019·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Davis NgarashiToru Nabika
Jun 26, 2020·European Journal of Clinical Pharmacology·Abolfazl AkbariSadegh Dehghani
Jan 8, 2021·Molecular Neurobiology·G MorrisB K Puri
Dec 18, 2020·Molecular Psychiatry·Xuechao FeiZhiqian Tong

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPase
nuclear translocation
ELISA
protein assay
Polymerase Chain Reaction
MDA

Software Mentioned

Image Lab TM
GraphPad Prism
GraphPad

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here