A neuroprotective role of kaempferol against chlorpyrifos-induced oxidative stress and memory deficits in rats via GSK3β-Nrf2 signaling pathway.

ملخص البحث

Pestic Biochem Physiol. 2018 Nov;152:29-37. doi: 10.1016/j.pestbp.2018.08.008. Epub 2018 Aug 13. A neuroprotective role of kaempferol against chlorpyrifos-induced oxidative stress and memory deficits in rats via GSK3β-Nrf2 signaling pathway. Hussein RM1, Mohamed WR2, Omar HA3. Author information Abstract Chlorpyrifos (CPF) is an agricultural pesticide and a potential food contaminant, which causes neurotoxicity. Here, we aimed at exploring the link between the repeated exposure to CPF and memory dysfunction in rats and the possible protective effect of kaempferol, a flavonoid with appreciable antioxidant and anti-inflammatory activities. Rats were divided into: Control group (received drug vehicles for 14 days); CPF-treated group (received subcutaneous 18 mg/kg BW of CPF daily for 14 days and CPF + Kaempferol treated group (received the same CPF dose +21 mg/kg BW of Kaempferol intraperitoneally for 14 days. On the 14th day, Y-maze and novel target recognition behavioral tests were employed to evaluate memory deficits. 24 h after the last dose of CPF, animals were sacrificed, and brain tissues were used for the determination of oxidative stress biomarkers and gene expression levels of GSK3β and Nrf2. The results revealed that CPF-treated rats suffered from severe deterioration of spatial and non-spatial memory functions with low activities of antioxidant enzymes and acetylcholinesterase (AChE). The administration of kaempferol significantly protected against CPF-induced neuronal damage, increased the activities of antioxidant enzymes and AChE and induced a better performance in the behavioral tests. The protective effect of kaempferol was mediated through the inhibition of GSK3β gene expression and the induction of Nrf2 expression in the brain tissues. In conclusion, the repeated exposure to CPF is associated with oxidative stress and memory deficits in rats. However, kaempferol administration effectively alleviated CPF- induced brain toxicity, possibly through the modulation of GSK3β-Nrf2 signaling pathway.

الكلمات المفتاحيه

Chlorpyrifos; GSK3β; Kaempferol; Neurotoxicity; Nrf2; Oxidative stress