Palliative potential of genistein to counteract endosulfan instigated colon toxicity via regulating TLR4/MyD88, JAK1/STAT3 and NF-κB pathway: A biochemical and histological approach

Abstract

Endosulfan (ESN) is an organophosphate insecticidal agent that is documented to induce various organ toxicities. Genistein (GEN) is a plant derived polyphenolic compound with excellent biological as well as pharmacological properties. This research was planned to assess the palliative potential of GEN to avert ENS prompted colonic toxicity. Albino rats (n = 36) were involved in this experiment that were divided into the control, ESN (5 mg/kg), ESN (5 mg/kg) + GEN (10 mg/kg), and GEN (10 mg/kg) alone treated group. We found that ENS intoxication upregulated the gene expression of STAT3, JAK1, TRAF6, MyD88, NF-κB, IL- IL-1β, TLR4, TNF-α, and IL-6 while reducing the gene expression of IκB. Moreover, ENS intoxication elevated the levelss of malondialdehyde (MDA) & reactive oxygen species (ROS) while decreasing the activties of glutathione reductase (GSR), catalase (CAT), heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), and glutathione S-transferase (GST). Furthermore, ESN administration notably escalated the concentrations of fecal calprotectin whereas reduced the concentrations of fecal elastase, lactase and sucrase. Besides, ESN intake upregulated the levels of Caspase-9, Bax and Caspase-3 while diminishing the levels of Bcl-2. Colonic histology was distorted after ESN provision. Nonetheless, GEN treatment remarkably protected the colonic tissues via regulating abovementioned irregularities owing to its marvelous anti-inflammatory, anti-apoptotic as well as antioxidant potential.