Cytoprotective properties of phenolic antidiarrheic ingredients in cultured astrocytes and neurons of rat brains

We have previously shown that particular phenolic antidiarrheic ingredients, including 2-methoxy-4-methylphenol (2M4MP) and 2-methoxy-4-ethyphenol (2M4EP), but not 2-methoxyphenol (2MP), significantly inhibit cellular maturation and differentiation of the bone-resorbing osteoclasts with concomitant protection of the bone-forming osteoblasts against oxidative stress by hydrogen peroxide (H2O2). In the present study, we evaluated the pharmacological actions of these three major phenolic antidiarrheic ingredients on the cellular viability in cultured astrocytes and neurons of the rat brain in vitro. Both 2M4MP and 2M4EP induced more efficient prevention of cell death induced by the brief exposure to 0.1 mM H2O2 for 2 h than 2MP upon simultaneous exposure in cultured rat cortical astrocytes. Similarly, both 2M4MP and 2M4EP were more effective than 2MP in significantly protecting the cytotoxicity by brief exposure to 0.1 mM H2O2 for 6 h in cultured rat hippocampal neurons, with concomitant suppression of the generation of intracellular reactive oxygen species in neurons exposed to H2O2. Moreover, the three ingredients not only significantly prevented cell death in hippocampal neurons exposed to 0.1 mM glutamate for 1 h when determined 48 h after the brief exposure, but also inhibited the generation of intracellular reactive oxygen species and the elevation of intracellular Ca2+ ions in neurons exposed to glutamate. These results suggest that particular phenolic antidiarrheic ingredients may prevent cell death through a mechanism related to diminution of the neurotoxicity of glutamate in neurons, in addition to eliciting cytoprotection against oxidative stress in astrocytes and neurons, in the rat brain.