Division of Nutrition and Metabolism, Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.
Department of Biochemistry, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey.
Pediatr Res. 2022 Aug;92(2):474-479. doi: 10.1038/s41390-021-01770-6. Epub 2021 Oct 9.
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.
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.
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.
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.
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.
尽管尼替西农治疗取得成功，但 1 型酪氨酸血症患者的长期并发症（包括肝细胞癌和智力下降）的病理生理学仍然不清楚。氧化应激可能在这些并发症中起作用。虽然增加的延胡索酰乙酰乙酸和马来酰乙酰乙酸会导致肝脏氧化应激，但增加的酪氨酸会导致大脑氧化应激。本研究旨在评估动态巯基/二硫键平衡作为晚期诊断的 1 型酪氨酸血症患者氧化应激的指标。
本研究纳入了 24 例（诊断年龄为 14.43±26.35 个月）晚期诊断的 1 型酪氨酸血症患者（19 例接受尼替西农治疗，5 例接受肝移植）和 25 名健康对照者。检测血清天然巯基、总巯基和二硫键水平，并根据这些值计算二硫键/天然巯基、二硫键/总巯基和天然巯基/总巯基的比值。
尽管尼替西农治疗组的血浆酪氨酸水平明显升高，但各组之间的天然巯基、总巯基和二硫键水平无显著差异，二硫键/天然巯基、二硫键/总巯基和天然巯基/总巯基比值也无升高。
我们认为，通过良好的依从性给予足够的代谢控制，用尼替西农进行治疗，有助于预防晚期诊断的 1 型酪氨酸血症患者的氧化应激。
尽管尼替西农（NTBC）治疗取得成功，但遗传性酪氨酸血症 1 型（HT1）患者长期并发症（包括肝细胞癌和智力下降）的潜在机制仍不清楚。氧化应激可能在这些并发症中起作用。尽管血浆酪氨酸水平较高且接受过肝移植的患者，NTBC 治疗下的遗传性酪氨酸血症患者的巯基/二硫键平衡（氧化应激的一个指标）并未受到干扰。这是首个评估动态巯基/二硫键平衡作为晚期诊断的 HT1 患者氧化应激指标的研究。
