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Effect of atorvastatin on AGEs-induced injury of cerebral cortex via inhibiting NADPH oxidase -NF-κB pathway in ApoE−/− mice

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Abstract

Advanced glycation end products (AGEs) are a group of modified proteins and/or lipids with damaging potential. AGEs-RAGE pathway plays a critical role to induce neurodegenerative encephalopathy. Statins can reduce the expression of AGEs-induced AGEs receptor (RAGE) in the aorta. It is not clear whether statins have potential benefits on AGEs-induced cognitive impairment. In this study, the effects of atorvastatin (ATV) on inflammation and oxidation stress in the cerebral cortex were investigated, and the underlying mechanisms were explored. Apolipoprotein E (ApoE)−/− male mice were divided into four groups: control, AGEs, AGEs + ALT711 (Alagebrium chloride) and AGEs + ATV. β-amyloid (Aβ) formation in the cerebral cortex was assessed through Congo red staining and the functional state of neurons was evaluated by Nissl’s staining. Immunostaining was performed to assess the accumulation of AGEs in the cerebral cortex. The expressions of mRNA and protein of RAGE, Nuclear factor kappa B (NF-κB) p65 and Nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) p47phox were detected by real-time polymerase chain reaction (PCR) and western blot. There were significant increases in AGEs deposit, Aβ formation, and the expressions of RAGE, NF-κB p65, and NADPH oxidase p47phox, and a decrease Nissl body in AGEs group compared with control group. ALT711 group recovered above change compared with AGEs group. Atorvastatin reduced Aβ formation and suppressed AGEs-induced expressions of NF-κB p65 and NADPH oxidase p47phox. Atorvastatin has little effects on AGEs deposit and RAGE expressions. Atorvastatin alleviates AGEs-induced neuronal impairment by alleviating inflammation and oxidative stress via inhibiting NADPH oxidase-NF-κB pathway.

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Data availability

The datasets used and analyzed during the current study are included in this published article.

Abbreviations

AGEs:

Advanced glycation end products

RAGE:

Receptor for AGEs

NF-κB:

Nuclear factor kappa B

ROS:

Reactive oxygen species

NADPH oxidase:

Nicotinamide adenine dinucleotide phosphate-oxidase

IL-1:

Interleukin-1

IL-6:

Interleukin-6

TNF-α:

Tumor necrosis factor-α

Aβ:

β-Amyloid

ApoE:

Apolipoprotein E

ATV:

Atorvastatin

BSA:

Bovine serum albumin

SEM:

Standard error

AD:

Alzheimer’s disease

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Acknowledgements

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Funding

This work was supported by grants from the Key Specialty Construction Project of Pudong Health and Family Planning Commission of Shanghai (PWZzk2017-12).

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Author notes

  1. Zhenhan Li and Peiye Yang have contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

    Zhenhan Li, Peiye Yang & Bo Feng

  2. Department of Pediatric Endocrinology, The Affiliated Wuxi Childern’s Hospital of Nanjing Medical University, Wuxi, China

    Peiye Yang

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  1. Zhenhan Li
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Contributions

ZL participated in the design of the study, carried out the immunohistochemistry, performed the statistical analysis and drafted the manuscript. PY carried out the animal experiment, RT-PCR and Western blot. BF conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Bo Feng.

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The authors declare that they have no competing interests.

Ethical approval and consent to participate

This study was conducted in accordance with the “Guide for the Care and Use of Laboratory Animals” prepared by the National Academy of Sciences and published by the National Institutes of Health and with the approval by the Ethical Committee on Animal Research at Shanghai East Hospital of Tongji University (Shanghai, China).

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Li, Z., Yang, P. & Feng, B. Effect of atorvastatin on AGEs-induced injury of cerebral cortex via inhibiting NADPH oxidase -NF-κB pathway in ApoE−/− mice. Mol Biol Rep 47, 9479–9488 (2020). https://doi.org/10.1007/s11033-020-05998-z

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