Luteolin protects microglia against rotenone-induced toxicity in a hormetic manner through targeting oxidative stress response, genes associated with Parkinson's disease and inflammatory pathways


Elmazoglu Z., YAR SAĞLAM A. S. , Sonmez C., KARASU Ç.

DRUG AND CHEMICAL TOXICOLOGY, cilt.43, sa.1, ss.96-103, 2020 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 43 Konu: 1
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1080/01480545.2018.1504961
  • Dergi Adı: DRUG AND CHEMICAL TOXICOLOGY
  • Sayfa Sayıları: ss.96-103

Özet

Rotenone, an environmental toxin, triggers Parkinson's disease (PD)-like pathology through microglia-mediated neuronal death. The effects and molecular mechanisms of flavonoid luteolin against rotenone-induced toxicity was assessed in microglial BV2 cells. Cells were pretreated with luteolin (1-50 mu M) for 12 h and then was co-treated with 20 mu M of rotenone for an additional 12 h in the presence of luteolin. The viability (MTT), IL-1 beta and TNF-alpha levels and lactate dehydrogenase (LDH) release (ELISA), and Park2, Lrrk2, Pink1, Nrf2 and Trx1 mRNA levels (qRT-PCR) were measured. In rotenone exposed microglia, luteolin increased viability significantly at lower concentrations (1-5 mu M) compared to higher concentrations (25-50 mu M). Rotenone increased LDH release and IL-1 beta levels in a dose-dependent manner (1-20 mu M). Luteolin inhibited rotenone-induced LDH release, however the activity decreased in concentration-dependent manner Neither rotenone nor luteolin altered TNF-alpha levels, but luteolin reduced IL-1 beta levels in a concentration dependent manner in rotenone exposed cells. The mRNA levels of Nrf2 and Trx1, which are the master regulators of redox state, were increased by rotenone, as well as by luteolin, which exhibited an inverse relationship between its concentration and effect (1-20 mu M). Park2 mRNA levels increased by luteolin, but decreased by rotenone. Pink1 mRNA levels was not altered by rotenone or luteolin. Lrrk2 mRNA levels reduced by luteolin, while it was increased by rotenone. Results suggest that luteolin have favorable effects on regulation of oxidative stress response, genes associated with PD and inflammatory pathways, hence protects microglia against rotenone toxicity in a hormetic manner.