Hepatoprotective, anti-apoptotic and anti-inflammatory efficacy of Quercetin or Rosemary extract against metalaxyl toxicity -induced liver damage in rats: A role of Nrf2/HO-1 signaling pathways

Abstract

Metalaxyl, a benzenoid fungicide, has hazardous effects on mammalian animals. Exposure to metalaxyl causes oxidative stress as well as clear toxicity. The possible protective impact of quercetin or rosemary extract against liver damage caused by the fungicide metalaxyl in rats were evaluated. Twenty-eight male albino rats split into four equal groups. G1 (control group); Rats were received distilled water. G2 (metalaxyl): Rats were administered oral dosages of metalaxyl (130 mg/kg b.wt) 1/10 LD₅₀ three times a week for six weeks. G3 (metalaxyl + quercetin): Rats were given 50 mg/kg b.wt/day of quercetin in addition to (130 mg/kg b.wt) of metalaxyl. G4 (metalaxyl + Rosemary extract): Rats were given (200 mg/kg b.wt/day) of Rosemary extract in addition to 130 mg/kg b.wt of metalaxyl. The findings showed that rats exposed to metalaxyl had markedly elevated levels of liver marker enzymes and clearly up-regulation of Caspase-3 gene expression. However, rats exposed to metalaxyl showed a considerable downregulation of the expression of the liver HO-1, Nrf2, and Bcl-2 genes. Conversely, Quercetin or Rosmary extract co-treatment with metalaxyl induce significant decreases in serum liver enzymes along with downregulation in caspase 3, while up-regulation of HO-1, Nrf2 and Bcl-2 gene expression in hepatocytes of treated rats. These results suggest that quercetin and rosemary extract may have a potential protective role as strong hepatoprotective, anti-inflammatory and anti-apoptotic properties, mitigate oxidative stress caused by metalaxyl toxicity induced -liver damage by inhibiting caspase 3 mediated initiation of HO-1, Nrf2 and Bcl-2 genes.