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Diphenyl Diselenide Attenuates Mitochondrial Damage During Initial Hypoxia and Enhances Resistance to Recurrent
Guilherme S Rieder1, Marcos M Braga1, Ben Hur M Mussulini2
1Programa 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.
Abstract:
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.
Insights
Diphenyl diselenide (PhSe)2 protects against hypoxia-induced brain damage and locomotor deficits in zebrafish. This compound enhances mitochondrial function and provides resistance to recurrent hypoxia, suggesting therapeutic potential for brain hypoxia diseases.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Pharmacology
Background:
- Hypoxia is a major factor in cerebral diseases, often leading to recurring episodes due to mitochondrial damage.
- Current treatments for hypoxia-related brain conditions are often insufficient, highlighting the need for novel therapeutic agents.
Purpose of the Study:
- To investigate the neuroprotective effects of diphenyl diselenide [(PhSe)2] in a zebrafish model of hypoxia.
- To assess the compound's ability to improve mitochondrial function and confer resistance to recurrent hypoxia.
Main Methods:
- Zebrafish were exposed to hypoxia and treated with diphenyl diselenide [(PhSe)2].
- Locomotor activity, brain mitochondrial respiration (electron transport system), and viability were evaluated.
- Resistance to recurrent hypoxia was assessed by measuring latency to symptom onset.
Main Results:
- Diphenyl diselenide [(PhSe)2] effectively crossed the blood-brain barrier and ameliorated hypoxia-induced locomotor impairments.
- The compound improved mitochondrial respiration by modulating complex III and enhanced mitochondrial viability in the telencephalon.
- Treatment with diphenyl diselenide [(PhSe)2] increased resistance to recurrent hypoxia.
Conclusions:
- Diphenyl diselenide [(PhSe)2] demonstrates significant neuroprotective effects against hypoxia and recurrent hypoxia in zebrafish.
- Cerebral mitochondria are a key target for the beneficial actions of diphenyl diselenide [(PhSe)2].
- Further research into diphenyl diselenide [(PhSe)2] is warranted for treating hypoxia-related brain pathologies.
