Prevention of fenitrothion induced hepatic toxicity by saponarin via modulating TLR4/MYD88, JAK1/STAT3 and NF-κB signaling pathways.

Abstract

Fenitrothion (FEN) is an organophosphate insecticidal agent that is considered as major source of organs toxicity. Saponarin (SAP) is a naturally occurring novel flavone that exhibits immense medicinal properties. The current trial was executed to evaluate the treatment potential of SAP against FEN instigated liver toxicity. Thirty-two male albino rats (Rattus norvegicus) were apportioned into four groups including control, FEN (10mg/kg), FEN (10mg/kg) + SAP (80mg/kg), and SAP (80mg/kg) alone treated group. It was revealed that FEN administration upregulated the gene expression of TNF-α, TLR4, IL-1β, MYD88, IL-6, TRAF6, COX-2, NF-κB, JAK1 and STAT3 while suppressing the gene expression of IκB. Moreover, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were promoted while the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (HO-1) and glutathione reductase (GSR) were suppressed after FEN provision. Furthermore, FEN administration notably escalated the concentrations of hepatic enzymes including alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) whereas reduced the concentrations of total proteins and albumin. Besides, FEN intake upregulated the levels of Caspase-9, Bax and Caspase-3 while diminishing the levels of Bcl-2. Hepatic histology was distorted after FEN provision. Nonetheless, SAP treatment remarkably protected the normal state of liver via regulating abovementioned irregularities. Our in-silico calculations confirm that SAP hold that potential to interact with binding pocket of these proteins, highlighting its ability as a therapeutic compound to alleviate FEN-induced liver damage.