Increased ROS levels, antioxidant defense disturbances and bioenergetic disruption induced by thiosulfate administration in the brain of neonatal rats.

Autor:	Glänzel NM; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil., da Rosa-Junior NT; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil., Signori MF; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil., de Andrade Silveira J; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil., Pinheiro CV; Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil., Marcuzzo MB; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil., Campos-Carraro C; Laboratório de Fisiologia Cardiovascular, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., da Rosa Araujo AS; Laboratório de Fisiologia Cardiovascular, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Schiöth HB; Functional Pharmacology and Neuroscience, Department of Surgical Sciences, Uppsala University, Uppsala, 75124, Sweden., Wajner M; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil.; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, Porto Alegre, 2350, 90035-903, RS, Brazil., Leipnitz G; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil. guilhian@ufrgs.br.; Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil. guilhian@ufrgs.br.; Functional Pharmacology and Neuroscience, Department of Surgical Sciences, Uppsala University, Uppsala, 75124, Sweden. guilhian@ufrgs.br.; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil. guilhian@ufrgs.br.; Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil. guilhian@ufrgs.br.
Jazyk:	angličtina
Zdroj:	Metabolic brain disease [Metab Brain Dis] 2024 Dec 20; Vol. 40 (1), pp. 73. Date of Electronic Publication: 2024 Dec 20.
DOI:	10.1007/s11011-024-01510-9
Abstrakt:	Sulfite oxidase deficiencies, either caused by deficiency of the apoenzyme or the molybdenum cofactor, and ethylmalonic encephalopathy are inherited disorders that impact sulfur metabolism. These patients present with severe neurodeterioration accompanied by cerebral cortex and cerebellum abnormalities, and high thiosulfate levels in plasma and tissues, including the brain. We aimed to clarify the mechanisms of such abnormalities, so we assessed the ex vivo effects of thiosulfate administration on energetic status and oxidative stress markers in cortical and cerebellar tissues of newborn rats. Thiosulfate (0.5 µmol/g) or PBS (vehicle) was injected into the fourth ventricle of rat pups. Thirty minutes after the injection, animals were euthanized and the brain structures were utilized for the experiments. Our data showed that thiosulfate decreased the reduced glutathione (GSH) concentrations, and superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) activities in the cortical structure. Thiosulfate also increased DCFH oxidation, hydrogen peroxide generation and glutathione reductase activity. In the cerebellum, thiosulfate reduced SOD and glutathione peroxidase activities but increased GST and CAT activities as well as DCFH oxidation. Regarding energy metabolism, thiosulfate specifically decreased complex IV activity in the cortex, whereas it increased cerebellar complex I and creatine kinase activities, indicating bioenergetic disturbances. The results suggest that the accumulation of thiosulfate causing redox disruption and bioenergetic alterations has a prominent role in the pathogenesis of sulfur metabolism deficiencies. Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee on the Use of Animals (CEUA) from UFRGS (project number 32807). Competing interests: The authors declare no competing interests. (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Full text from SpringerLink