Troxerutin downregulates C/EBP-β gene expression via modulating the IFNγ-ERK1/2 signaling pathway to ameliorate rotenone-induced retinal neurodegeneration

J Biochem Mol Toxicol. 2020 Jun;34(6):e22482. doi: 10.1002/jbt.22482. Epub 2020 Mar 1.

Abstract

Troxerutin, a natural flavonoid guards against oxidative stress and apoptosis with a high capability of passing through the blood-brain barrier. Our aim was to investigate the role of troxerutin in experimentally induced retinal neurodegeneration by modulating the interferon-gamma (IFNγ)-extracellular signal-regulated kinases 1/2 (ERK1/2)-CCAAT enhancer-binding protein β (C/EBP-β) signaling pathway. Three groups of rats (10 each group) were included. Group I (control group), group II (rotenone treated group): the rats were injected subcutaneously with a single rotenone dosage of 3 mg/kg repeated every 48 hours for 60 days to trigger retinal neurodegeneration. Group III (troxerutin-treated group): rats received troxerutin (150 mg/kg/day) by oral gavage 1 hour before rotenone administration. A real-time polymerase chain reaction technique was applied to measure messenger RNA (mRNA) levels of retinal C/EBP-β. Enzyme-linked immunosorbent assay technique was utilized to assay tumor necrosis factor-α (TNF-α), IFNγ, and ERK1/2 levels. Finally, reactive oxygen species (ROS), as well as carbonylated protein (CP) levels, were assessed spectrophotometrically. Improved retinal neurodegeneration by downregulation of C/EBP-β mRNA gene expression, also caused a significant reduction of TNF-α, IFNγ, ERK1/2 as well as ROS and CP levels compared with the diseased group. These findings could hold promise for the usage of troxerutin as a protective agent against rotenone-induced retinal neurodegeneration.

Keywords: C/EBP-β; ERK1/2; IFNγ; rotenone; troxirutin.

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / genetics*
  • Disease Models, Animal
  • Down-Regulation / drug effects*
  • Gene Expression / drug effects*
  • Hydroxyethylrutoside / administration & dosage
  • Hydroxyethylrutoside / analogs & derivatives*
  • Interferon-gamma / metabolism*
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Neurodegenerative Diseases / chemically induced*
  • Neurodegenerative Diseases / complications
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Protective Agents / administration & dosage*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Retinal Diseases / chemically induced*
  • Retinal Diseases / complications
  • Retinal Diseases / drug therapy*
  • Retinal Diseases / metabolism
  • Rotenone / adverse effects*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Cebpb protein, rat
  • Hydroxyethylrutoside
  • Protective Agents
  • RNA, Messenger
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Rotenone
  • troxerutin
  • Interferon-gamma