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

被引：14

作者：

Mounier, Noha M. ^{[1
]}

Wahdan, Sara A. ^{[2
]}

Gad, Amany M. ^{[1
,3
]}

Azab, Samar S. ^{[2
]}

机构：

[1] Egyptian Drug Author EDA, Cairo, Egypt

[2] Ain Shams Univ, Fac Pharm, Dept Pharmacol & Toxicol, Cairo, Egypt

[3] Sinai Univ, Fac Pharm, Dept Pharmacol & Toxicol, East Kantara Branch, El Ismailia, Egypt

来源：

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY | 2021年 / 394卷 / 07期

关键词：

Doxorubicin; Atorvastatin; Cognitive impairment; ER stress; Inflammation; Oxidative stress; Heme oxygenase-1; COA REDUCTASE INHIBITORS; CENTRAL-NERVOUS-SYSTEM; HIPPOCAMPAL NEUROGENESIS; NEUROLOGICAL DISORDERS; ALZHEIMER-DISEASE; DRUG ADRIAMYCIN; CARBON-MONOXIDE; STATINS; CARDIOTOXICITY; INVOLVEMENT;

D O I：

10.1007/s00210-021-02081-7

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：1537 / 1551

页数：15

共 74 条

[1] Efficiency of Atorvastatin in the Protection of Anthracycline-Induced Cardiomyopathy [J].