Neuroprotective Effect of 3-[(4-Chlorophenyl)selanyl]-1-methyl-1H-indole on Hydrogen Peroxide-Induced Oxidative Stress in SH-SY5Y Cells.

Extensive data have reported the involvement of oxidative stress in the pathogenesis of neuropsychiatric disorders, prompting the pursuit of antioxidant molecules that could become adjuvant pharmacological agents for the management of oxidative stress-associated disorders. The 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole (CMI) has been reported as an antioxidant and immunomodulatory compound that improves depression-like behavior and cognitive impairment in mice. However, the exact effect of CMI on specific brain cells is yet to be studied. In this context, the present study aimed to evaluate the antioxidant activity of CMI in H2O2-induced oxidative stress on human dopaminergic neuroblastoma cells (SH-SY5Y) and to shed some light into its possible mechanism of action. Our results demonstrated that the treatment of SH-SY5Y cells with 4 µM CMI protected them against H2O2 (343 µM)-induced oxidative stress. Specifically, CMI prevented the increased number of reactive oxygen species (ROS)-positive cells induced by H2O2 exposure. Furthermore, CMI treatment increased the levels of reduced glutathione in SH-SY5Y cells. Molecular docking studies demonstrated that CMI might interact with enzymes involved in glutathione metabolism (i.e., glutathione peroxidase and glutathione reductase) and H2O2 scavenging (i.e., catalase). In silico pharmacokinetics analysis predicted that CMI might be well absorbed, metabolized, and excreted, and able to cross the blood-brain barrier. Also, CMI was not considered toxic overall. Taken together, our results suggest that CMI protects dopaminergic neurons from H2O2-induced stress by lowering ROS levels and boosting the glutathione system. These results will facilitate the clinical application of CMI to treat nervous system diseases associated with oxidative stress.

Toxicological evaluation of 3-(4-Chlorophenylselanyl)-1-methyl-1H-indole through the bovine oocyte in vitro maturation model.

The development of new bioactive molecules based on the molecular hybridization has been widely explored. In line with this, reliable tests should be employed to give information about the toxicology of these new molecules. In this sense, the use of in vitro tests is a valuable tool, especially the in vitro maturation of oocytes (IVM), which is an efficient resource to discover the potential toxicity of synthetic molecules. Thus, the aim of the present study was to evaluate the toxicological effects of the selenium-containing indolyl compound 3-(4-Chlorophenylselanyl)-1-methyl-1H-indole (CMI), on different quality parameters of bovine oocytes through the IVM. Different concentrations of the CMI compound (0, 25, 50, 100, 200 µM) were supplemented during the in vitro maturation process. After, the oocyte maturation rate, glutathione (GSH) levels, reactive oxygen species (ROS) levels, membrane, and mitochondrial integrity were evaluated. The results showed that the lowest concentration of CMI induced the highest GSH production (P < 0.05), an important marker of cytoplasmic quality and maturation. All treatments increased ROS production in relation to non-supplementation (P < 0.05). In addition, oocyte maturation was reduced only with the highest concentration of CMI (P < 0.05). Supplementation with CMI did not impact mitochondrial activity, integrity and cell membrane. To our knowledge, this is the first study that evaluates CMI on the oocyte in vitro maturation process. Importantly, our results did not find any toxic effect of CMI on bovine oocytes. CMI was efficient for cytoplasmic maturation by promoting an increase in the intracellular levels of glutathione.