Neuroprotective effect of melatonin against kainic acid-induced oxidative injury in hippocampal slice culture of rats.

Hyung Kim,Bae Lee,Kyung Lee

doi:10.3390/ijms15045940

Abstract

Endogenous melatonin is a known free radical scavenger that removes reactive oxygen species (ROS), thus, alleviating oxidative stress. The purpose of this study was to demonstrate its effect against kainic acid (KA)-induced oxidative stress in organotypic hippocampal slice cultures (OHSCs). To observe neuroprotective effects of melatonin, different concentrations (0.01, 0.1 and 1 mM) of melatonin were administrated after KA treatment for 18 h in OHSCs of rat pups. Dose-response studies showed that neuronal cell death was significantly reduced after 0.1 and 1 mM melatonin treatments based on propidium iodide (PI) uptake and cresyl violet staining. The dichlorofluorescein (DCF) fluorescence which indicates ROS formation decreased more in the melatonin-treated group than in the KA group. The expression of 5-lipoxigenase (5-LO) and caspase-3 were reduced in the melatonin-treated groups compared to the KA group. These results suggest that melatonin may be an effective agent against KA-induced oxidative stress in the OHSC model.

Highlights

It is well known that the excessive production of oxygen free radicals may generate neuronal disorders
propidium iodide (PI) uptake was used to investigate the effects of melatonin on kainic acid (KA)-induced neuronal injury
KA-induced injury is related to generation of reactive oxygen species (ROS), which has a neurotoxic effect in the hippocampus

Summary

Introduction

It is well known that the excessive production of oxygen free radicals may generate neuronal disorders. The brain is one of the most oxygen consuming organs [1]; reactive oxygen species (ROS) production in the brain is higher than in the rest of the body. An antioxidant maintains and regulates the equilibrium between ROS formation and extinction. If the equilibrium is disrupted, ROS act as a stressor and damage intracellular elements such as proteins, lipids, and DNA. Because neuronal cells are especially sensitive and vulnerable to ROS, apoptosis or necrosis can occur [2]. Oxidative stress produces neurotoxicity in the brain. Mitochondrial oxidative stress has frequently been associated with various neuronal disorders [3]

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