Epigenetic impact and ameliorative potential role of quercetin or rosemary extract on metalaxy or manganese chloride-induced toxicity via mitigation of microRNA, DNA methylation and regulation of MAPK phosphorylation in rats

Abstract

Metalaxyl fungicide, play an important role in hepatotoxicity and liver damage. High levels of Manganese (Mn) exposure may cause irreversible brain disease. The potential protective role and epigenetic mechanism of Quercetin or rosemary extract in metalaxyl or manganese chloride (MnCl₂) toxicity were evaluated. Fifty-sex rats were split into two experiment. Experiment A: Metalaxyl hepetotoxicity 1/10 LD₅₀ (130 mg/kg b.wt) and Experiment B: Manganese chloride neurotoxicity 1/25 LD₅₀ (59.36 mg/kg b.wt). The experiment (A) divided into 4 groups: G1 (control group) given distilled water, G2 (Metalaxyl) received (130 mg/kg b.wt) three times a week for six weeks, G3 (Metalaxyl + Quercetin) given quercetin (50 mg/kg b.wt/day) and metalaxyl.  G4 (Metalaxyl + Rosemary extract) given rosemary extract (200 mg/kg b.wt/day) and Metalaxyl. The experiment (B) split also into four equal groups similar the design in experiment (A) but MnCl₂ (59.36 mg/kg b.wt) was given five times a week for six consecutive weeks. The results of metalaxyl exposed rats displayed up-regulation of liver MAPK1, miRNA-684 and DNA hypermethylation but, down-regulation of miRNA-7, up-regulation of miRNA-153 were detected in brain of MnCl₂ intoxicated rats compared to control. Quercetin or rosmary extract co-treatment with metalaxy significantly down-regulated liver MAPK1 and miRNA-684 with DNA hypomethylation with up-regulation of miRNA-7 and down-regulation of miRNA-153 in brain of MnCl₂ exposed rats. In conclusion, quercetin or rosmary extract displayed hepatoprotective and neuroprotective role against metalaxyl or manganese toxicity via mitigation of epigenetic markers MicroRNA, DNA Methylation and regulation of MAPK phosphorylation in liver and brain of rats.