Courtes 2019 Biomed Pharmacother

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Courtes AA, de Carvalho NR, Gonçalves DF, Hartmann DD, da Rosa PC, Dobrachinski F, Franco JL, de Souza DOG, Soares FAA (2019) Guanosine protects against Ca2+-induced mitochondrial dysfunction in rats. Biomed Pharmacother 111: 1438-46.

» Open Access

Courtes AA, de Carvalho NR, Goncalves DF, Hartmann DD, da Rosa PC, Dobrachinski F, Franco JL, de Souza DOG, Soares FAA (2019) Biomed Pharmacother

Abstract: Mitochondria play an important role in cell life and in the regulation of cell death. In addition, mitochondrial dysfunction contributes to a wide range of neuropathologies. The nucleoside Guanosine (GUO) is an endogenous molecule, presenting antioxidant properties, possibly due to its direct scavenging ability and/or from its capacity to activate the antioxidant defense system. GUO demonstrate a neuroprotective effect due to the modulation of the glutamatergic system and maintenance of the redox system. Thus, considering the few studies focused on the direct effects of GUO on mitochondrial bioenergetics, we designed a study to evaluate the in vitro effects of GUO on rat mitochondrial function, as well as against Ca2+-induced impairment. Our results indicate that GUO prevented mitochondrial dysfunction induced by Ca2+ misbalance, once GUO was able to reduce mitochondrial swelling in the presence of Ca2+, as well as ROS production and hydrogen peroxide levels, and to increase manganese superoxide dismutase activity, oxidative phosphorylation and tricarboxylic acid cycle activities. Our study indicates for the first time that GUO could direct prevent the mitochondrial damage induced by Ca2+ and that these effects were not related to its scavenging properties. Our data indicates that GUO could be included as a new pharmacological strategy for diseases linked to mitochondrial dysfunction.

Keywords: Nucleoside, Guanine-based purine, Calcium, High-resolution respirometry Bioblast editor: Plangger M O2k-Network Lab: BR Sao Gabriel Franco JL


Labels: MiParea: Respiration, Pharmacology;toxicology 


Organism: Rat  Tissue;cell: Liver  Preparation: Isolated mitochondria  Enzyme: Complex II;succinate dehydrogenase  Regulation: Calcium  Coupling state: LEAK, OXPHOS  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k, O2k-Fluorometer 

2019-02, Amplex UltraRed