Oxidative Stress in Homocystinuria Due to Cystathionine ß-Synthase Deficiency: Findings in Patients and in Animal Models

Faverzani, Jéssica Lamberty; Hammerschmidt, Tatiane Grazieli; Sitta, Ângela; Deon, Marion; Wajner, Moaçir; Vargas, Carmen Regla

doi:10.1007/s10571-017-0478-0

Cited by 39 publications

(33 citation statements)

References 42 publications

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“…Oxidative stress may play an important role in the pathophysiology of homocystinuria, as deduced from studies carried out in patients and animal models [ 129 ]. Protein, lipid, and DNA oxidative damage and decreased antioxidant defences have been found in patients [ 130 – 132 ].…”

Section: Homocystinuriamentioning

confidence: 99%

Altered Redox Homeostasis in Branched‐Chain Amino Acid Disorders, Organic Acidurias, and Homocystinuria

Richard

Gallego

Rivera-Barahona

et al. 2018

Oxidative Medicine and Cellular Longevity

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Inborn errors of metabolism (IEMs) are a group of monogenic disorders characterized by dysregulation of the metabolic networks that underlie development and homeostasis. Emerging evidence points to oxidative stress and mitochondrial dysfunction as major contributors to the multiorgan alterations observed in several IEMs. The accumulation of toxic metabolites in organic acidurias, respiratory chain, and fatty acid oxidation disorders inhibits mitochondrial enzymes and processes resulting in elevated levels of reactive oxygen species (ROS). In other IEMs, as in homocystinuria, different sources of ROS have been proposed. In patients' samples, as well as in cellular and animal models, several studies have identified significant increases in ROS levels along with decreases in antioxidant defences, correlating with oxidative damage to proteins, lipids, and DNA. Elevated ROS disturb redox-signaling pathways regulating biological processes such as cell growth, differentiation, or cell death; however, there are few studies investigating these processes in IEMs. In this review, we describe the published data on mitochondrial dysfunction, oxidative stress, and impaired redox signaling in branched-chain amino acid disorders, other organic acidurias, and homocystinuria, along with recent studies exploring the efficiency of antioxidants and mitochondria-targeted therapies as therapeutic compounds in these diseases.

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Section: Homocystinuriamentioning

confidence: 99%

Altered Redox Homeostasis in Branched‐Chain Amino Acid Disorders, Organic Acidurias, and Homocystinuria

Richard

Gallego

Rivera-Barahona

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…While the value of reproducibility is well recognized, few such studies occur in rare diseases. For instance, in a recent review of oxidative stress and inflammatory markers studies in CBSDH three of six publications were by the same author involving a common cohort at a single service . All studies had a small number of subjects.…”

Section: Discussionmentioning

confidence: 94%

“…Previous work has reported that vitamin C therapy, an antioxidant, ameliorated endothelial vascular dysfunction assessed as brachial artery endothelium‐dependent flow‐mediated dilation (FMD) in CBSDH . Human studies have implicated oxidative stress and inflammation as candidate pathogenic mechanisms in CBSDH. Similar findings were reported in mouse models of CBSDH.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of oxidative stress, inflammation, and vascular dysfunction in inherited cystathionine β‐synthase deficient homocystinuria and the impact of taurine treatment in a phase 1/2 human clinical trial

Hove

Freehauf

Fıçıcıoğlu

et al. 2019

J of Inher Metab Disea

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Study Objective: A phase 1/2 clinical trial was performed in individuals with cystathionine β synthase (CBS) deficient homocystinuria with aims to: (a) assess pharmacokinetics and safety of taurine therapy, (b) evaluate oxidative stress, inflammation, and vascular function in CBS deficiency, and (c) evaluate the impact of short-term taurine treatment. Methods: Individuals with pyridoxine-nonresponsive CBS deficiency with homocysteine >50 μM, without inflammatory disorder or on antioxidant therapy were enrolled. Biomarkers of oxidative stress and inflammation, endothelial function (brachial artery flow-mediated dilation [FMD]), and disease-related metabolites obtained at baseline were compared to normal values. While maintaining current Johan L. K. Van Hove and Cynthia L. Freehauf contributed equally to this study. Lucienne Driskill Foundation; William R. Hummel Homocystinuria Research Fund treatment, patients were treated with 75 mg/kg taurine twice daily, and treatment response assessed after 4 hours and 4 days. Results: Fourteen patients (8-35 years; 8 males, 6 females) were enrolled with baseline homocysteine levels 161 ± 67 μM. The study found high-dose taurine to be safe when excluding preexisting hypertriglyceridemia. Taurine pharmacokinetics showed a rapid peak level returning to near normal levels at 12 hours, but had slow accumulation and elevated predosing levels after 4 days of treatment. Only a single parameter of oxidative stress, 2,3-dinor-8-isoprostaglandin-F2α, was elevated at baseline, with no elevated inflammatory parameters, and no change in FMD values overall. Taurine had no effect on any of these parameters. However, the effect of taurine was strongly related to pretreatment FMD values; and taurine significantly improved FMD in the subset of individuals with pretreatment FMD values <10% and in individuals with homocysteine levels >125 μM, pertinent to endothelial function. Conclusion: Taurine improves endothelial function in CBS-deficient homocystinuria in patients with preexisting reduced function. K E Y W O R D Sclinical trial, endothelial function, homocystinuria, inflammation, oxidative stress, taurine

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“…. Patients with both primary hypertension and hyper homocysteine are known as having H‐type hypertension. Enneman et al .…”

Section: Discussionmentioning

confidence: 99%

Higher concentration of serum C‐terminal cross‐linking telopeptide of type I collagen is positively related with inflammatory factors in postmenopausal women with H‐type hypertension and osteoporosis

Chen

Wei

2019

Orthopaedic Surgery

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ObjectiveTo investigate the changes of inflammatory factors and bone metabolism markers in postmenopausal women with H‐type hypertension and to assess the relationship between them.MethodsPostmenopausal women who were diagnosed with osteoporosis were selected as observation objects. Participants were divided into three groups: only osteoporosis group (osteoporosis group), hypertension combined with osteoporosis group (hypertension group), and H‐type hypertension combined with osteoporosis group (H‐type hypertension group). The changes in bone mineral density and bone metabolic markers (osteocalcin [OC], procollagen type I N‐terminal propeptide (PINP), and C‐terminal cross‐linking telopeptide of type I collagen [CTX]) and inflammatory factors (interleukin‐6 [IL‐6] and tumor necrosis factor‐α [TNF‐α]) were compared among three groups.ResultsIn the hypertension group and the H‐type hypertension group, the bone mineral density of the lumbar spine (0.647 ± 0.038 vs 0.638 ± 0.034 vs 0.668 ± 0.047, P < 0.05) and the femoral neck (0.567 ± 0.047 vs 0.552 ± 0.053 vs 0.618 ± 0.059, P < 0.05) was significantly lower than that in the osteoporosis group. The concentrations of CTX (266.61 ± 64.65 vs 293.09 ± 72.34 vs 235.48 ± 62.85, P < 0.05), IL‐6 (44.36 ± 6.45 vs 48.05 ± 8.04 vs 39.06 ± 7.95, P < 0.05) and TNF‐α (30.53 ± 6.28 vs 34.52 ± 7.15 vs 28.66 ± 6.19, P < 0.01) in the hypertension group and in the H‐type hypertension group were significantly higher than those in the osteoporosis group. The concentrations of OC (30.59 ± 6.43 vs 27.10 ± 6.51, P < 0.05) and PINP (36.36 ± 6.16 vs 33.16 ± 6.77, P < 0.05) in the H‐type hypertension group were increased dramatically. The concentration of CTX was positively correlated with the concentration of IL‐6 (r = 0.587, P < 0.01) and TNF‐α (r = 0.474, P < 0.01) and negatively related with the concentration of OC (r = −0.591, P < 0.01) and PINP (r = −0.646, P < 0.01) and the bone mineral density of the lumbar spine (r = −0.470, P < 0.01) and the femoral neck (r = −0.509, P < 0.01).ConclusionHigher concentration of serum CTX is found in postmenopausal women with H‐type hypertension, which is positively correlated with inflammatory factors. Besides, H‐type hypertension could further enhance the activity of osteoclasts and increase the expressions of inflammatory factors, resulting in the aggravation of osteoporosis.

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Oxidative Stress in Homocystinuria Due to Cystathionine ß-Synthase Deficiency: Findings in Patients and in Animal Models

Cited by 39 publications

References 42 publications

Altered Redox Homeostasis in Branched‐Chain Amino Acid Disorders, Organic Acidurias, and Homocystinuria

Altered Redox Homeostasis in Branched‐Chain Amino Acid Disorders, Organic Acidurias, and Homocystinuria

Biomarkers of oxidative stress, inflammation, and vascular dysfunction in inherited cystathionine β‐synthase deficient homocystinuria and the impact of taurine treatment in a phase 1/2 human clinical trial

Higher concentration of serum C‐terminal cross‐linking telopeptide of type I collagen is positively related with inflammatory factors in postmenopausal women with H‐type hypertension and osteoporosis

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