Role of melatonin on calcium signaling and mitochondrial oxidativestress in epilepsy: focus on TRP channels

Abstract

Calcium ion (Ca 2+ ) accumulation and excessive oxidative stress in the hippocampus and brain cortex have long been known as major contributors to the etiology of epilepsy. I have reviewed the role of Ca 2+ signaling through cation channels and mitochondriamediated oxidative stress on epilepsy in human and animals. A review of the relevant papers and results from recent studies were obtained from PubMed and the Science Citation Index. Current literature findings indicate that melatonin and agomelatine reduce activation of hippocampal transient receptor potential (TRP), glutamate receptors, and voltage-gated calcium channels that are critical for the development of abnormal Ca 2+ homeostasis and oxidative stress and associated mitochondrial dysfunction. In addition, low doses of melatonin induce anticonvulsant action through increase of GABA levels in the hippocampus and brain cortex. The accumulating evidence implicates a modulator role of melatonin on excessive oxidative stress products, plus mitochondrial and Ca 2+ dysregulations in epilepsy. The evidence indicates that modulation of oxidative stress and neuronal Ca 2+ handling occurs through effects on TRP channels, suggesting an increasingly viable approach for therapeutic interventions against epilepsy.

Melatonin increased vitamin C and antioxidant enzyme values in the plasma,heart, liver, and kidney of Adriamycin-treated rats

“…These findings are partially consistent with the results concerning decreases in CAT, SOD, and GSH-Px with melatonin (Özdoğan et al, 2011;Lee et al, 2013). The accumulating evidence implicates a modulatory role of melatonin on excessive oxidative stress induced in Adriamycin toxicity (Othman et al, 2008;Lee et al, 2013;Escribano et al, 2014) and some stimulative agents (Nazıroğlu et al, 2012;Şenol et al, 2014;Nazıroğlu, 2015).…”

“…Oxidative stress is characterized as an imbalance between antioxidant defense systems and reactive oxygen species and nitrogen reactive substances (Nazıroğlu, 2007(Nazıroğlu, , 2015. One practice used for minimizing the oxidative stress induced by Adriamycin is the administration of some antioxidants to experimental animals.…”

The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels

“…Accumulating evidences indicated that activations of TRPM2 and TRPV1 channels are increased in brain injury-induced mitochondrial activation and excessive Free oxygen radical production by the excessive mitochondrial Ca 2+ uptake6929. Furthermore, DEX induces antioxidant effects in the spinal cord (DRG) injuries and cerebral ischemia (hippocampus) of rats11819.…”

Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats

“…The activation of PARP has been shown to lead to DNA injury, and PARP activity in the brain is markedly increased after OVX induction (Siegel and McCullough 2013). Indeed, previous studies have shown that there is a strong relationship between oxidative stress and PARP activation in the brain after OVX induction (Zhang et al 2007;Ying and Xiong 2010) and that oxidative stress in neurons can induce PARP activation (Nazıroğlu 2007;Nazıroğlu 2015).…”