Zinc-induced protective effect for testicular ischemia-reperfusion injury by promoting antioxidation via microRNA-101-3p/Nrf2 pathway

Aging (Albany NY). 2019 Nov 5;11(21):9295-9309. doi: 10.18632/aging.102348. Epub 2019 Nov 5.

Abstract

The present study was performed to determine the protective effect of Zinc on the rat testicular ischemia-reperfusion (I/R) injury and its mechanism. In vivo, the pathological changes and the apoptosis index were significantly relieved in the rats with Low-dose Zinc pretreatment, compared to the I/R group. After Low-dose Zinc treatment, the levels of tissue Malondialdehyde (MDA) were significantly decreased, while tissue antioxidant indices were significantly increased. Meanwhile, the level of NF-κB was significantly lower compared to I/R group, while the levels of Nrf2-dependent antioxidant enzymes were significantly higher in Low-dose Zinc+I/R group. In vitro, Low-dose Zinc markedly increased Leydig cell (TM3) cell viability, and relieved testicular oxidative damage via down-regulating ROS. A total of 22 differently expressed microRNAs were screened out using microRNA microarray in rat testicular tissue caused by I/R injury, especially showing that miR-101-3p was selected as the target miRNA. Furthermore, the levels of Nrf2 and NF-κB were apparently increased/decreased in TM3 cells treated with Hypoxic/Reoxygenation (H/R) after miR-101-3p mimics/inhibitor. In addition, H/R-induced testicular oxidative damage was recovered in TM3 administrated with miR-101-3p inhibitor and si-Nrf2. Therefore, this study provided a novel insight for investigating protective effect of Zinc on testicular I/R injury by promoting antioxidation via miR-101-3p/Nrf2.

Keywords: antioxidation; microRNA-101-3p; testicular ischemia-reperfusion injury; zinc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical
  • Male
  • MicroRNAs / metabolism*
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*
  • Signal Transduction / drug effects
  • Testicular Diseases / prevention & control*
  • Testis / blood supply
  • Testis / drug effects
  • Trace Elements / pharmacology
  • Trace Elements / therapeutic use*
  • Zinc / pharmacology
  • Zinc / therapeutic use*

Substances

  • MIRN101 microRNA, rat
  • MicroRNAs
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, rat
  • Trace Elements
  • Zinc