Protective role of isobenzofuran-1(3H)-one derivative against neuronal injury and enzyme activity dysregulation induced by bipyridyl herbicide in adult male rats

Abstract

Diquat (DQT) is a bipyridyl herbicide widely used in agriculture. The exposure to DQT may overwhelm the antioxidant system, leading to oxidative damage in organs such as the brain, liver, and kidneys. The brain is particularly susceptible to oxidative damage because of its high oxygen consumption, relatively low antioxidant levels, and limited regenerative capacity. Faced with stressful agents, using compounds capable of repairing and replacing oxidized biomolecules is a promising option to maintain redox homeostasis. Isobenzofuran-1 (3H)-one derivative (named compound 1) emerges as a potential candidate to control the redox imbalance induced by DQT in the brain. The present study aimed to explore the neurotoxicity mechanisms of DQT and the antioxidant potential of compound 1 within the hippocampus and cortex, brain regions impacted by AD, using in vitro and in vivo models. Treatment with compound 1 reduced intracellular levels of ROS and lipid peroxidation in primary cultures of hippocampal neurons caused by DQT. Moreover, compound 1 significantly elevated GSH levels in the brains of rats subjected to DQT treatment. Treatment with compound 1 also decreased lipid peroxidation and carbonylated protein levels in the brain induced by DQT. The exposure to DQT resulted in neuronal injury in the hippocampus. Compound 1, protected against neuronal damage in CA1 and dentate gyrus hippocampal regions. The findings of our study suggest that DQT leads to oxidative damage and neuronal death in both the hippocampus and the cortex. Furthermore, compound 1 exhibits neuroprotective qualities by reducing oxidative damage caused by exposure to DQT.