遗传性血色素沉着症患者的辅酶 Q10 缺乏。

Coenzyme Q10 deficiency in patients with hereditary hemochromatosis.

机构信息

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Tecnología Farmacéutica, Buenos Aires, Argentina.

Universidad de Buenos Aires, Facultad de Medicina, División de Gastroenterología, Sección Hepatología, Hospital de Clínicas José de San Martin, Buenos Aires, Argentina.

出版信息

Clin Res Hepatol Gastroenterol. 2021 Nov;45(6):101624. doi: 10.1016/j.clinre.2021.101624. Epub 2021 Mar 4.

DOI:10.1016/j.clinre.2021.101624

PMID:33676282

Abstract

AIM

Hereditary hemochromatosis (HH) is a group of inherited disorders that causes a slow and progressive iron deposition in diverse organs, particularly in the liver. Iron overload induces oxidative stress and tissue damage. Coenzyme Q10 (CoQ10) is a cofactor in the electron-transport chain of the mitochondria, but it is also a potent endogenous antioxidant. CoQ10 interest has recently grown since various studies show that CoQ10 supplementation may provide protective and safe benefits in mitochondrial diseases and oxidative stress disorders. In the present study we sought to determine CoQ10 plasma level in patients recently diagnosed with HH and to correlate it with biochemical, genetic, and histological features of the disease.

METHODS

Plasma levels of CoQ10, iron, ferritin, transferrin and vitamins (A, C and E), liver tests (transaminases, alkaline phosphatase and bilirubin), and histology, as well as three HFE gene mutations (H63D, S654C and C282Y), were assessed in thirty-eight patients (32 males, 6 females) newly diagnosed with HH without treatment and in twenty-five age-matched normolipidemic healthy subjects with no HFE gene mutations (22 males, 3 females) and without clinical or biochemical signs of iron overload or liver diseases.

RESULTS

Patients with HH showed a significant decrease in CoQ10 levels respect to control subjects (0.31 ± 0.03 µM vs 0.70 ± 0.06 µM, p < 0.001, respectively) independently of the genetic mutation, cirrhosis, transferrin saturation, ferritin level or markers of hepatic dysfunction. Although a decreasing trend in CoQ10 levels was observed in patients with elevated iron levels, no correlation was found between both parameters in patients with HH. Vitamins C and A levels showed no changes in HH patients. Vitamin E was significantly decreased in HH patients (21.1 ± 1.3 µM vs 29.9 ± 2.5 µM, p < 0.001, respectively), but no correlation was observed with CoQ10 levels.

CONCLUSION

The decrease in CoQ10 levels found in HH patients suggests that CoQ10 supplementation could be a safe intervention strategy complementary to the traditional therapy to ameliorate oxidative stress and further tissue damage induced by iron overload.

摘要

目的

遗传性血色素沉着症（HH）是一组遗传性疾病，导致铁在不同器官中缓慢而渐进地沉积，特别是在肝脏中。铁过载会引起氧化应激和组织损伤。辅酶 Q10（CoQ10）是线粒体电子传递链的辅助因子，但它也是一种有效的内源性抗氧化剂。最近，由于各种研究表明 CoQ10 补充可能对线粒体疾病和氧化应激障碍提供保护和安全益处，因此 CoQ10 的兴趣有所增加。在本研究中，我们试图确定最近诊断为 HH 的患者的 CoQ10 血浆水平，并将其与疾病的生化、遗传和组织学特征相关联。

方法

评估 38 例未经治疗的新诊断为 HH 的患者（32 名男性，6 名女性）和 25 例年龄匹配的无 HFE 基因突变（22 名男性，3 名女性）、无脂质异常且无 HFE 基因突变的健康对照者（22 名男性，3 名女性）的 CoQ10、铁、铁蛋白、转铁蛋白和维生素（A、C 和 E）水平、肝试验（转氨酶、碱性磷酸酶和胆红素）以及三种 HFE 基因突变（H63D、S654C 和 C282Y）的血浆水平和组织学特征。

结果

与对照组相比，HH 患者的 CoQ10 水平显著降低（分别为 0.31±0.03 µM 和 0.70±0.06 µM，p<0.001），独立于基因突变、肝硬化、转铁蛋白饱和度、铁蛋白水平或肝功能障碍标志物。尽管在铁水平升高的患者中观察到 CoQ10 水平呈下降趋势，但在 HH 患者中未发现两者之间存在相关性。HH 患者的维生素 C 和 A 水平没有变化。HH 患者的维生素 E 显著降低（分别为 21.1±1.3 µM 和 29.9±2.5 µM，p<0.001），但与 CoQ10 水平无相关性。