Effects of Selenium and Topiramate on Cytosolic Ca2+ Influx and Oxidative Stress in Neuronal PC12 Cells

Abstract

It has been widely suggested that selenium (Se) deficiency play an important role in the pathophysiology of epilepsy. It has been reported that Se provides protection against the neuronal damage in patients and animals with epilepsy by restoring the antioxidant defense mechanism. The neuroprotective effects of topiramate (TPM) have been reported in several studies but the putative mechanism of action remains elusive. We investigated effects of Se and TPM in neuronal PC12 cell by evaluating Ca(2+) mobilization, lipid peroxidation and antioxidant levels. PC12 cells were divided into eight groups namely control, TPM, Se, H(2)O(2), TPM + H(2)O(2), Se + H(2)O(2), Se + TPM and Se + TPM + H(2)O(2). The toxic doses and times of H(2)O(2), TPM and Se were determined by cell viability assay which is used to evaluate cell viability. Cells were incubated with 0.01 mM TPM for 5 h and 500 nM Se for 10 h. Then, the cells were exposed to 0.1 mM H(2)O(2) for 10 h before analysis. The cells in all groups except control, TPM and Se were exposed to H(2)O(2) for 15 min before analysis. Cytosolic Ca(2+) release and lipid peroxidation levels were higher in H(2)O(2) group than in control, Se and TPM combination groups although their levels were decreased by incubation of Se and TPM combination. However, there is no difference on Ca(2+) release in TPM group. Glutathione peroxidase activity, reduced glutathione and vitamin C levels in the cells were lower in H(2)O(2) group than in control, Se and TPM groups although their values were higher in the cells incubated with Se and TPM groups than in H(2)O(2) groups. In conclusion, these results indicate that Se induced protective effects on oxidative stress in PC12 cells by modulating cytosolic Ca(2+) influx and antioxidant levels. TPM modulated also lipid peroxidation and glutathione and vitamin C concentrations in the cell system.

Neuroprotective effects of various doses of topiramate against methylphenidate induced oxidative stress and inflammation in rat isolated hippocampus

“…These studies showed that TPM has been proposed as a putative agent in the treatment of some neurodegenerative disorders . Recent studies have suggested that the mechanism of action of TPM in neuroprotection is the inhibition of Ca 2+ ion entry and Protein kinase C (PKC) . Recent findings also suggest that TPM can attenuate oxidative stress and mitochondrial dysfunction .…”

Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells

“…These proteins, to a certain degree, affect caspase activation by controlling the release of cytochrome C from the mitochondria, which in turn interacts with the adapter protein Apaf-1, resulting in the activation of pro-Caspase-9 (30). The disturbance of intracellular free Ca 2+ ions is another key event when cells are exposed to damaging stress (31–33). In the present study, apoptosis was inhibited in MDR cells.…”

Protective Effects of Riboflavin and Selenium on Brain Microsomal Ca2+-ATPase and Oxidative Damage Caused by Glyceryl Trinitrate in a Rat Headache Model

“…If the free radical production increases proportionally to the consumption of GSH-Px enzyme activities, GSH levels also decline. Recently, we observed a decrease in Ca 2+ entry, MMCA activity, and oxidative stress values in experimental neuronal diseases such as epilepsy and pain, although selenium administration induced protective effects on the values in human, rat, and cell lines [15][16][17]37]. The results of a few reports indicated that oxidative stress levels were high in patients with migraines and rats with CSD [6,7,11].…”

“…Selenium is incorporated in mammalian proteins as selenocysteine or selenomethionine, both of which are dietary forms of selenium, although selenomethionine is the major form [13,14]. Selenium is implicated as the neuroprotective agent in several neuronal diseases including epilepsy [15,16] and pain [17]. The neuroprotective effects of selenium are attributed to its ability to inhibit apoptosis and mitochondrial oxidative stress [18] and to modulate Ca 2+ influx through cation channels such as TRP melastatin 2 (TRPM2) channels [19,20].…”