Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul;394(7):1537-1551.
doi: 10.1007/s00210-021-02081-7. Epub 2021 Mar 23.

Role of inflammatory, oxidative, and ER stress signaling in the neuroprotective effect of atorvastatin against doxorubicin-induced cognitive impairment in rats

Noha M Mounier  1 , Sara A Wahdan  2 , Amany M Gad  1   3 , Samar S Azab  4
Affiliations

Role of inflammatory, oxidative, and ER stress signaling in the neuroprotective effect of atorvastatin against doxorubicin-induced cognitive impairment in rats

Noha M Mounier et al. Naunyn Schmiedebergs Arch Pharmacol. 2021 Jul.

Retraction in

Abstract

Doxorubicin (DOX) is a potent chemotherapeutic agent widely used for the treatment of several malignancies. Despite its effectiveness, DOX has been implicated in induced neurotoxicity manifested as cognitive dysfunction with varying degrees, commonly referred to as chemobrain. DOX-induced chemobrain is presumed to be due to cytokine-induced inflammatory, oxidative, and apoptotic responses damaging the brain. Atorvastatin (ATV), 3-hydroxy 3-methylglutaryl co-enzyme A (HMG Co-A) reductase inhibitor, is a cholesterol-lowering statin possessing beneficial pleiotropic effects, including anti-inflammatory, antioxidant, and anti-apoptotic properties. Therefore, this study aims to investigate the potential neuroprotective effects of ATV against DOX-induced cognitive impairment studying the possible involvement of heme oxygenase-1 (HO-1) and endoplasmic reticulum (ER) stress biomarkers. Rats were treated with DOX (2 mg/kg/week), i.p. for 4 weeks. Oral treatment with ATV (10 mg/kg) ameliorated DOX-induced behavioral alterations, protected brain histological features, and attenuated DOX-induced inflammatory, oxidative, and apoptotic biomarkers. In addition, ATV upregulated the protective HO-1 expression levels and downregulated the DOX-induced apoptotic ER stress biomarkers. In conclusion, ATV (10 mg/kg) exhibited neuroprotective properties against DOX-induced cognitive impairment which could possibly be attributed to their anti-inflammatory, antioxidant, and anti-apoptotic effects in the brain.

Keywords: Atorvastatin; Cognitive impairment; Doxorubicin; ER stress; Heme oxygenase-1; Inflammation; Oxidative stress.

PubMed Disclaimer

References

    1. Acar Z, Kale A, Turgut M, Demircan S, Durna K, Demir S, Meriç M, Ağaç MT (2011) Efficiency of atorvastatin in the protection of anthracycline-induced cardiomyopathy. J Am Coll Cardiol 58:988–989 - PubMed
    1. Ali AE, Mahdy HM, Elsherbiny DM, Azab SS (2018) Rifampicin ameliorates lithium-pilocarpine-induced seizures, consequent hippocampal damage and memory deficit in rats: impact on oxidative, inflammatory and apoptotic machineries. Biochem Pharmacol 156:431–443 - PubMed
    1. Aluise CD, Sultana R, Tangpong J, Vore M, Clair DS, Moscow JA, Butterfield DA (2010) Chemo brain (chemo fog) as a potential side effect of doxorubicin administration: role of cytokine-induced, oxidative/nitrosative stress in cognitive dysfunction. Chemo Fog. Springer, pp. 147-156
    1. Banchrof J, Steven A, Turner D (1996) Theory and practice of histopathological techniques. Churchil Livingstone, New York, London, San Francisco, Tokyo
    1. Barone E, Di Domenico F, Butterfield DA (2014a) Statins more than cholesterol lowering agents in Alzheimer disease: their pleiotropic functions as potential therapeutic targets. Biochem Pharmacol 88:605–616 - PubMed

Publication types

MeSH terms

LinkOut - more resources