The effect of Crocin on TFAM and PGC-1α expression and Catalase and Superoxide dismutase activities following cholestasis-induced neuroinflammation in the striatum of male Wistar rats

Metab Brain Dis. 2021 Oct;36(7):1791-1801. doi: 10.1007/s11011-021-00748-x. Epub 2021 May 21.

Abstract

Bile secretion is a physiological function that is disrupted following Bile Duct Ligation (BDL) and induces cholestasis. Cholestasis is a bile flow reduction that induces apoptosis, oxidative stress, and inflammation, and alters the expression of genes. Evidence shows the relationship between cholestasis and neuroinflammation. Cholestasis via attenuating mitochondrial biogenesis and anti-oxidant activity can induce neuroinflammation and apoptosis. Mitochondrial transcriptional factor A (TFAM) and Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) are involved in mitochondrial biogenesis, and TFAM, PGC-1α, Catalase (CAT), and Superoxide dismutase (SOD) have a role in upregulating antioxidant pathways. On the other hand, many studies have shown the neuroprotective effects of Crocin, the water-soluble carotenoid of Saffron (Crocus sativus L.). In this study, we aimed to investigate the effect of Crocin on the level of TFAM, PGC-1α, CAT, and SOD following cholestasis-induced neuroinflammation in the rat's striatum. Cholestasis was induced by BDL surgery and administration of Crocin was intraperitoneal, at the dose of 30 mg/kg every day, 24 h after BDL surgery up to thirty days. The results showed that TFAM, PGC-1α, and SOD were decreased following cholestasis; while, CAT was increased. In addition, Crocin restored the effects of cholestasis on the level of TFAM, PGC-1α, and SOD. In conclusion, Crocin may have improvement effects on cholestasis-induced neuroinflammation in the rat's striatum.

Keywords: Catalase (CAT); Crocin; Mitochondrial transcriptional factor A (TFAM); Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α); Striatum; Superoxide dismutase (SOD).

MeSH terms

  • Animals
  • Carotenoids / pharmacology
  • Carotenoids / therapeutic use
  • Catalase / metabolism
  • Cholestasis* / complications
  • Cholestasis* / drug therapy
  • Cholestasis* / metabolism
  • Male
  • Neuroinflammatory Diseases*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Transcription Factors
  • Vitamin B 12 / analogs & derivatives

Substances

  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Tfam protein, rat
  • Transcription Factors
  • factor A
  • Carotenoids
  • crocin
  • Catalase
  • Superoxide Dismutase
  • Vitamin B 12