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

Pesticidal agents are considered as “Cornerstone” in agriculture sector owing to their marvelous potential to counteract various pest species (Serrão et al., 2022). However, due to their intensive applications, the use of pesticides has become a challenge for aquatic as well as terrestrial ecosystems (Rahman et al., 2020). Fenitrothion (FEN) is an organophosphate insecticidal drug that is employed to retard the growth of agricultural insects in various crops (Wang et al., 2012, Espinoza Navarro et al., 2017). It is estimated that FEN production reached 15,000–20000 tons annually around the globe (WHO, 2018). Numerous investigations have elucidated the residual presences of FEN in foods, embryos of chicken and green beans that ultimately become the part of our food web (Malhat, 2012, WHO, 2019).

Furthermore, FEN administration reduces the activity of cholinesterase in brain, lungs and serum that is directly associated with escalated levels of oxidative stress in aforementioned vital organs (Abdel-Ghany et al., 2016). FEN exposure dysregulates the gene profile of CYP1A1 and CYP1A2 in hepatic tissues of rats (Abd-Elhakim et al., 2021). Ibrahim et al. (2021) elucidated that FEN intoxication escalates the levels of oxidative stress markers in hepatic tissues. Galal et al. (2019) observed an escalation in the levels of inflammatory as well as oxidative biomarkers after FEN administration. FEN intoxication escalates the levels of ROS in hepatic tissues which is considered as the core reason underlying various sorts of hepatic pathologies (Elhalwagy et al., 2008). Moreover, FEN administration damages the DNA of hepatocytes that ultimately leads toward the onset of hepatic impairments (Zeid and Khalil, 2014). These findings suggest the need of a novel therapeutic agent to avert FEN induced hepatotoxicity.

Plant based flavonoids are widely used to alleviate a wide range of hepatic injuries (Sahu et al., 2023). Saponarin (SAP) is a naturally occurring novel flavone that is extracted from Hordeum vulgare L. (Kantharaj et al., 2023). SAP demonstrated extensive pharmacological features including anti-inflammatory (Min et al., 2021), antioxidant (Simeonova et al., 2013), hypolipidemic (Kim et al., 2022) as well as reduce the tendency to sleep disorders (Kim et al., 2022). Numerous investigations have revealed the influence of SAP on different signaling pathways (Seo et al., 2014, Min et al., 2021). Therefore, the current experimental trial was conducted to evaluate the medicinal value of SAP against FEN induced hepatotoxicity in rats via regulating biochemical and histological parameters.

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