Pharmacotherapeutic potential of pratensein to avert metribuzin instigated hepatotoxicity via regulating TGF-β1, PI3K/Akt, Nrf-2/Keap-1 and NF-κB pathway

Metribuzin (MBN) is a selective herbicide that adversely damages the vital organs of the body including the liver. Pratensein (PTN) is a novel flavonoid that exhibits marvelous medicinal properties. This experimental trial commenced to elucidate the pharmacotherapeutic strength of PTN to counteract MBN provoked liver toxicity in rats. Thirty-six male albino rats (Rattus norvegicus) were categorized into four groups i.e., the control, MBN (133.33 mg/kg), MBN (133.33 mg/kg) + PTN (20 mg/kg) and PTN (20 mg/kg) alone treated group. Our findings revealed that MBN exposure promoted the expressions of Keap-1 as well as concentrations of ROS and MDA while reducing the gene expressions of Nrf-2 as well as activities of catalase (CAT), glutathione Peroxidase (GPx), glutathione reductase (GSR), heme oxygenase-1 (HO-1), superoxide dismutase (SOD) and glutathione (GSH) contents. The levels of albumin and total proteins were reduced whereas the levels of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were enhanced following the MBN administration. Moreover, the gene expression of transforming growth Factor–β1 (TGF-β1), matrix metallopeptidase-2 (MMP-2), matrix metallopeptidase-9 (MMP-9), collagen, type I, alpha 1 and type-3 alpha were escalated in response to MBN intoxication. Furthermore, MBN administration cause a sudden upregulation in the levels of NF-κB, IL-1β, TNF-α, IL-6 & COX-2. Besides, MBN exposure enhanced the gene expression of Bax and Caspase-3 while reducing the gene expression of PI3K, Akt and Bcl-2. Additionally, MBN exposure dysregulated the normal histology of liver. However, PTN treatment notably protected the hepatic tissues via regulating abovementioned dysregulations due to its marvelous ROS scavenging potential.