Ameliorative effects of omega-3 against profenofos-induced neurotoxicity in rats via PI3K/AKT pathway

Abstract

Profenofos (PFF) is a class of organophosphate insecticides and acaricides. The poison is mainly neurotoxic that causes pest death by affecting acetylcholinesterase activity. The health of the brain is significantly influenced by omega-3 (long chain polyunsaturated fatty acids). It is mostly found in fish rich in fat. Although omega-3 has been shown in numerous studies to have anti-inflammatory and antioxidant properties in the brain, it is unknown how it affects PI3K/AKT-mediated apoptosis in brain toxicity. In Wistar rats subjected to PFF-induced neurotoxicity, the current study sought to evaluate the ameliorative effects of omega-3 on brain function (cerebral cortex), oxidative stress, and PI3K/AKT-mediated apoptosis. Twenty-eight male Wistar rats were divided into four equal groups. The following were the groups of rats: Group 1 (G1) remained a healthy control group. For four weeks, G2 received daily omega-3 at a dose of 100 mg/kg b.wt. G3 received PFF at a dose of 35 mg/kg b.wt. twice a week. G4 received an omega-3 at the same dose and duration one hour prior to the PFF injection. The findings demonstrated that omega-3 reduces the brain dysfunctions brought on by PFF by reestablishing the levels of MDA, GSH, SOD, triglycerides, cholesterol, and cholinesterase activity. Furthermore, the pro-inflammatory NFκB/STAT-3 mRNA gene expression was repressed and the anti-inflammatory PI3K/AKT mRNA gene expression was stimulated. In addition, Caspase-3 (Cas-3) and Tumor necrosis factor-alpha (TNF-α) immunohistochemistry area% were markedly lower with only a limited number of neurons displaying mild to moderate immunostaining, indicating a notable reduction in apoptotic glial cells and inflammation. By lessening the degenerative alterations, omega-3 also lessens the impact of inflammation on the cerebral cortex. In conclusion, omega-3 has the potential to ameliorate PFF sub-acute toxicity induced brain dysfunction by targeting PI3K/AKT pathway.