Melatonin neuroprotection of the hippocampus exposed to diclofenac sodium during pre- and postnatal life

Abstract

Diclofenac sodium (DS), a phenyl acetic acid derivative, is a potent inhibitor of cyclooxygenase that has been extensively used worldwide for many years in the treatment of inflammation and pain. However, despite these benefits, it also exhibits numerous adverse effects on the central nervous system, especially when used prenatally. Melatonin (MLT) is a neuroendocrine substance largely produced in the brain. It has been shown to exhibit several properties, including antioxidant, anti-inflammatory, and antiapoptotic effects, and acts as a neuroprotective agent. MLT exhibits pleiotropic neurobiological effects via cell membrane receptors. Pyramidal and granular neurons in the hippocampus contain MLT membrane receptors (MT1 and MT2). In this chapter, we discuss the cellular and molecular mechanisms of DS-induced reactive oxygen species generation in the hippocampus, the molecular targets, and responses, how oxidative stress affects hippocampus functions, and the MLT mechanism of action in terms of potential protection against DS-induced toxicity.