Diphenyl Diselenide Attenuates Mitochondrial Damage During Initial Hypoxia and Enhances Resistance to Recurrent Hypoxia.

Autor: Rieder GS; Programa de Pós Graduação Em Bioquímica Toxicológica, Departamento de Bioquímica E Biologia Molecular, Centro de Ciências Naturais E Exatas, Universidade Federal de Santa Maria, Avenida Roraima 1000, Santa Maria, RS, 97105-900, Brazil., Braga MM; Programa de Pós Graduação Em Bioquímica Toxicológica, Departamento de Bioquímica E Biologia Molecular, Centro de Ciências Naturais E Exatas, Universidade Federal de Santa Maria, Avenida Roraima 1000, Santa Maria, RS, 97105-900, Brazil., Mussulini BHM; Programa de Pós-Graduação Em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil., Silva ES; Programa de Pós-Graduação Em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil., Lazzarotto G; Programa de Pós-Graduação Em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil., Casali EA; Programa de Pós-Graduação Em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil., Oliveira DL; Programa de Pós-Graduação Em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil., Franco JL; Universidade Federal Do Pampa, Campus São Gabriel, São Gabriel, RS, Brazil., Souza DOG; Programa de Pós-Graduação Em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil., Rocha JBT; Programa de Pós Graduação Em Bioquímica Toxicológica, Departamento de Bioquímica E Biologia Molecular, Centro de Ciências Naturais E Exatas, Universidade Federal de Santa Maria, Avenida Roraima 1000, Santa Maria, RS, 97105-900, Brazil. joao.rocha@ufsm.br.
Jazyk: angličtina
Zdroj: Neurotoxicity research [Neurotox Res] 2024 Feb 09; Vol. 42 (1), pp. 13. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1007/s12640-024-00691-6
Abstrakt: Hypoxia plays a significant role in the development of various cerebral diseases, many of which are associated with the potential risk of recurrence due to mitochondrial damage. Conventional drug treatments are not always effective for hypoxia-related brain diseases, necessitating the exploration of alternative compounds. In this study, we investigated the potential of diphenyl diselenide [(PhSe) 2 ] to ameliorate locomotor impairments and mitigate brain mitochondrial dysfunction in zebrafish subjected to hypoxia. Additionally, we explored whether these improvements could confer resistance to recurrent hypoxia. Through a screening process, an appropriate dose of (PhSe) 2 was determined, and animals exposed to hypoxia received a single intraperitoneal injection of 100 mg/kg of the compound or vehicle. After 1 h from the injection, evaluations were conducted on locomotor deficits, (PhSe) 2 content, mitochondrial electron transport system, and mitochondrial viability in the brain. The animals were subsequently exposed to recurrent hypoxia to assess the latency time to hypoxia symptoms. The findings revealed that (PhSe) 2 effectively crossed the blood-brain barrier, attenuated locomotor deficits induced by hypoxia, and improved brain mitochondrial respiration by modulating complex III. Furthermore, it enhanced mitochondrial viability in the telencephalon, contributing to greater resistance to recurrent hypoxia. These results demonstrate the beneficial effects of (PhSe) 2 on both hypoxia and recurrent hypoxia, with cerebral mitochondria being a critical target of its action. Considering the involvement of brain hypoxia in numerous pathologies, (PhSe) 2 should be further tested to determine its effectiveness as a potential treatment for hypoxia-related brain diseases.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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