Quercetin or Rosmary extract mitigates Manganese chloride-induced Neurotoxicity through Regulation of DNA Methylation and Histone Acetylation and alleviation of apoptosis in rats

Abstract

Manganese (Mn) is a necessary trace mineral, but imbalanced levels in the body can lead to neurotoxicity. The neurotoxicity of manganese chloride (MnCl2) is associated with dopaminergic neurodegeneration, oxidative damage and neuro-inflammation. This study was conducted to assess the neuroprotective effects of quercetin or rosemary extract on neurotoxicity induced by MnCl2 in rats. Twenty-eight male albino rats were separated into four identical groups.  G1(normal control): Rats were provided with purified water. G2 (MnCl₂): Rats were orally administered MnCl2 at a dose of 1/25 LD50 (59.36 mg/kg b.wt) five times a week for six consecutive weeks. G3 (MnCl₂+ Quercetin): Rats were given MnCl2 (59.36 mg/kg b.wt) along with Quercetin (50 mg/kg b.wt/day).   G4 (MnCl₂+ Rosemary extract): Rats were given MnCl2 (59.36 mg/kg b.wt) along with Rosemary extract (200 mg/kg b.wt/day). Results indicated that a significant upregulation of HAT1, HDAC1, and Phosphatidylinositol 3 kinase (PI3K) gene expression with Global DNA hyper-methylation were observed in brain of MnCl₂ exposed rats. Meanwhile, Quercetin or Rosmary extract co-treatment with MnCl₂ induce significant downregulation of HAT1,HDAC1 and PI3K  expression with major Global DNA hypo-methylation in the brain of rats. Additionally, treating manganese-exposed rats with quercetin or Rosemary extract also resulted in the preservation of the brain's histological structure. This results suggest that quercetin and rosemary can modulate alterations in histone acetylation in rats brain cells when exposed to manganese through their antioxidant, anti-inflammatory, and anti-apoptotic properties.