Evaluation of dynamic thiol/disulfide homeostasis in hereditary tyrosinemia type 1 patients.

Autor: Aktuglu Zeybek AC; Division of Nutrition and Metabolism, Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey. dracaz@iuc.edu.tr., Kiykim E; Division of Nutrition and Metabolism, Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey., Neselioglu S; Department of Biochemistry, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey., Iscan HZ; Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey., Zubarioglu T; Division of Nutrition and Metabolism, Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey., Cansever MS; Vocational School of Health Services, Department of Medical Services and Techniques, Istanbul University-Cerrahpasa, Istanbul, Turkey., Erel O; Department of Biochemistry, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey.
Jazyk: angličtina
Zdroj: Pediatric research [Pediatr Res] 2022 Aug; Vol. 92 (2), pp. 474-479. Date of Electronic Publication: 2021 Oct 09.
DOI: 10.1038/s41390-021-01770-6
Abstrakt: Background: Despite successful treatment with nitisinone, the pathophysiology of long-term complications, including hepatocellular carcinoma and mental decline in tyrosinemia type 1 patients, is still obscure. Oxidative stress may play a role in these complications. While increased fumarylacetoacetate and maleylacetoacetate cause oxidative stress in the liver, increased tyrosine causes oxidative stress in the brain. The aim of this study is to evaluate dynamic thiol/disulfide homeostasis as an indicator of oxidative stress in late-diagnosed tyrosinemia type 1 patients.
Methods: Twenty-four late-diagnosed (age of diagnosis; 14.43 ± 26.35 months) tyrosinemia type 1 patients (19 under nitisinone treatment and 5 with liver transplantation) and 25 healthy subjects were enrolled in the study. Serum native thiol, total thiol, and disulfide levels were measured, and disulfide/native, disulfide/total, and native thiol/total thiol ratios were calculated from these values.
Results: No significant difference was observed in native, total, and disulfide thiol levels between the groups and no increase in disulfide/native, disulfide/total, and native/total thiol ratios was detected, despite significantly higher plasma tyrosine levels in the nitisinone-treated group.
Conclusions: We suggest that providing sufficient metabolic control with good compliance to nitisinone treatment can help to prevent oxidative stress in late-diagnosed tyrosinemia type 1 patients.
Impact: Despite successful nitisinone (NTBC) treatment, the underlying mechanisms of long-term complications in hereditary tyrosinemia type 1 (HT1), including hepatocellular carcinoma and mental decline, are still obscure. Oxidative stress may play a role in these complications. Thiol/disulfide homeostasis, which is an indicator of oxidative stress, is not disturbed in hereditary tyrosinemia patients under NTBC treatment, despite higher plasma tyrosine levels and patients who had liver transplantation. This is the first study evaluating dynamic thiol/disulfide homeostasis as an indicator of oxidative stress in late-diagnosed HT1 patients.
(© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)
Databáze: MEDLINE
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