Evaluation of neuroprotective activity of digoxin and semisynthetic derivatives against partial chemical ischemia.

Autor: de Souza Gonçalves B; Laboratório de Bioquímica Celular, Universidade Federal de São João del Rei, Divinópolis, Minas Gerais, Brazil., de Moura Valadares JM; Laboratório de Bioquímica Celular, Universidade Federal de São João del Rei, Divinópolis, Minas Gerais, Brazil., Alves SLG; Laboratório de Síntese Orgânica e Nanoestruturas, Universidade Federal de São João del Rei, Divinópolis, Minas Gerais, Brazil., Silva SC; Laboratório de Síntese Orgânica e Nanoestruturas, Universidade Federal de São João del Rei, Divinópolis, Minas Gerais, Brazil., Rangel LP; Laboratório de Bioquímica Tumoral, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Cortes VF; Laboratório de Bioquímica Celular, Universidade Federal de São João del Rei, Divinópolis, Minas Gerais, Brazil., Villar JAFP; Laboratório de Síntese Orgânica e Nanoestruturas, Universidade Federal de São João del Rei, Divinópolis, Minas Gerais, Brazil., Barbosa LA; Laboratório de Bioquímica Celular, Universidade Federal de São João del Rei, Divinópolis, Minas Gerais, Brazil., de Lima Santos H; Laboratório de Bioquímica Celular, Universidade Federal de São João del Rei, Divinópolis, Minas Gerais, Brazil.
Jazyk: angličtina
Zdroj: Journal of cellular biochemistry [J Cell Biochem] 2019 Oct; Vol. 120 (10), pp. 17108-17122. Date of Electronic Publication: 2019 Jul 16.
DOI: 10.1002/jcb.28971
Abstrakt: Recently, cardiotonic steroids (CTS) have been shown to lead to the activation of Na,K-ATPase at low concentrations in brain, promoting neuroprotection against ischemia. We report here the results of the use of digoxin and its semisynthetic derivatives BD-14, BD-15, and BD-16 against partial chemical ischemic induction followed by reperfusion in murine neuroblastoma cells neuro-2a (N2a). For chemical ischemic induction, sodium azide (5 mM) was used for 5 hours, and then reperfusion was induced for 24 hours. Na,K-ATPase activity and protein levels were analyzed in membrane preparation of N2a cells pretreated with the compounds (150 nM), in the controls and in induced chemical ischemia. In the Na,K-ATPase activity and protein levels assays, the steroids digoxin and BD-15 demonstrated a capacity to modulate the activity of the enzyme directly, increasing its levels of expression and activity. Oxidative parameters, such as superoxide dismutase (SOD) activity, lipid peroxidation (thiobarbituric acid reactive substance), glutathione peroxidase (GPx), glutathione (GSH) levels, hydrogen peroxide content, and the amount of free radicals (reactive oxygen species) during induced chemical ischemia were also evaluated. Regarding the redox state, lipid peroxidation, hydrogen peroxide content, and GPx activity, we have observed an increase in the chemical ischemic group, and a reduction in the groups treated with CTS. SOD activity increased in all treated groups when compared to control and GSH levels decreased when treated with sodium azide and did not change with CTS treatments. Regarding the lipid profile, we saw a decrease in the content of phospholipids and cholesterol in the chemical ischemic group, and an increase in the groups treated with CTS. In conclusion, the compounds used in this study demonstrate promising results, since they appear to promote neuroprotection in cells exposed to chemical ischemia.
(© 2019 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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