2. Academic Validation
  3. ALDH2 attenuates early-stage STZ-induced aged diabetic rats retinas damage via Sirt1/Nrf2 pathway

ALDH2 attenuates early-stage STZ-induced aged diabetic rats retinas damage via Sirt1/Nrf2 pathway

  • Life Sci. 2018 Dec 15;215:227-235. doi: 10.1016/j.lfs.2018.10.019.
Mengshan He 1,  Pan Long 2,  Weiming Yan 2,  Tao Chen 2,  Lunfeng Guo 3,  Zouming Zhang 4,  Siwang Wang 5
Affiliations

Affiliations

  • 1 Department of Chinese Material Medical and Natural Medicines, Air Force Medical University, Xi'an, Shaanxi, China.
  • 2 Center of Clinical Aerospace Medicine, Air Force Medical University, Xi'an, Shaanxi, China.
  • 3 Department of Pharmacy, Central Hospital of Ankang City, Ankang, Shaanxi, China.
  • 4 Center of Clinical Aerospace Medicine, Air Force Medical University, Xi'an, Shaanxi, China. Electronic address: zhangzm@fmmu.edu.cn.
  • 5 Department of Chinese Material Medical and Natural Medicines, Air Force Medical University, Xi'an, Shaanxi, China. Electronic address: wangsiw@fmmu.edu.cn.
PMID: 30315856 DOI: 10.1016/j.lfs.2018.10.019
Abstract

Aims: Acetaldehyde dehydrogenase 2 (ALDH2) was reported for its protective properties on myocardial damage, stroke and neurodegeneration disease, but the effects and mechanisms of ALDH2 in the modulation of diabetic retinopathy remain unclear. The present study evaluated the protection effects of ALDH2 on streptozocin (STZ)-induced aged diabetic rats retinas damage.

Main methods: 24 aged male diabetic Sprague-Dawley (SD) rats induced by a single intraperitoneal injection of STZ were randomly divided into Alda1-treated group and dimethylsulfoxide (DMSO) group. Rats were intraperitoneally injected with 10 mg/kg ALDH2 activator Alda1 (or DMSO) 3 days before STZ injection and 30 days afterwards. A series of detections on retinal structural, functional and molecular levels were applied at 1 d, 7 d and 30 d after aged diabetic rats model established.

Key findings: Optical coherence tomography (OCT) revealed that the thickness of outer nuclear layer (ONL) and whole retinas in Alda1-treated group were thicker than DMSO group. Full field electroretinograms (ffERG) showed a higher amplitude wave (dark-adaptation 3.0 and OPs) in Alda1-treated group. In addition, the levels of retinal tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) from Alda1-treated group were lower whereas superoxide dismutase (SOD) activity was notably higher. Moreover, the expressions of ALDH2, silence information regulation factor 2 related Enzyme I (SIRT1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in Alda1-treated group retinas were significantly increased, while the expression of vascular endothelial growth factor (VEGF-α) was dramatically decreased.

Significance: ALDH2 could ameliorate early-stage STZ-induced aged diabetic rats retinas damage possibly via increasing SIRT1 and Nrf2 expression.

Keywords

ALDH2; Aged rats; Nrf2; STZ-induced diabetes; Sirt1; VEGF-α.

Figures
Products