Amelioration of serum 8-OHdG level by enzyme replacement therapy in patients with Fabry cardiomyopathy

Kuan-Hsuan Chen; Yueh-Ching Chou; Chen-Yuan Hsiao; Yueh Chien; Kang-Ling Wang; Ying-Hsiu Lai; Yuh-Lih Chang; Dau-Ming Niu; Wen-Chung Yu

doi:10.1016/j.bbrc.2017.03.030

Amelioration of serum 8-OHdG level by enzyme replacement therapy in patients with Fabry cardiomyopathy

Biochem Biophys Res Commun. 2017 Apr 29;486(2):293-299. doi: 10.1016/j.bbrc.2017.03.030. Epub 2017 Mar 12.

Authors

Kuan-Hsuan Chen¹, Yueh-Ching Chou², Chen-Yuan Hsiao³, Yueh Chien⁴, Kang-Ling Wang⁵, Ying-Hsiu Lai⁴, Yuh-Lih Chang⁶, Dau-Ming Niu⁷, Wen-Chung Yu⁸

Affiliations

¹ Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Pharmacy, Taipei, Veterans General Hospital, Taipei, Taiwan, ROC.
² Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Pharmacy, Taipei, Veterans General Hospital, Taipei, Taiwan, ROC; School of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROC.
³ Department of Surgery, National Yang-Ming University Hospital, Taipei, Taiwan, ROC.
⁴ Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
⁵ School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
⁶ Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Pharmacy, Taipei, Veterans General Hospital, Taipei, Taiwan, ROC.
⁷ Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Pediatrics, Taipei, Veterans General Hospital, Taipei, Taiwan, ROC.
⁸ School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. Electronic address: wcyu@vghtpe.gov.tw.

PMID: 28300554
DOI: 10.1016/j.bbrc.2017.03.030

Abstract

Objectives: The level of 8-hydroxy-2-deoxyguanosise (8-OHdG) is a marker of oxidative stress. The objective of this study was to evaluate the effect of enzyme replacement therapy (ERT) on the level of 8-OHdG in patients with Fabry cardiomyopathy and the clinical evolution of Fabry cardiomyopathy.

Methods: We measured the serum levels of 8-OHdG in 20 healthy control and 22 patients with Fabry cardiomyopathy before and after ERT.

Results: The mean lysoGb3 and 8-OHdG levels was significantly increased in patients with Fabry cardiomyopathy compared with that of control subjects (lysoGb3, 3.6 ± 1.1 nM vs. 0.4 ± 0.1 nM, p < 0.01; 8-OHdG, 4.5 ± 0.5 ng/mL vs. 3.4 ± 0.4 ng/mL, P < 0.05). The mean lysoGb3 and 8-OHdG levels was significantly reduced after ERT for 14.2 months (lysoGb3, 3.6 ± 1.1 nM vs. 2.9 ± 1.1 nM, P < 0.05; 8-OHdG, 4.5 ± 0.5 ng/mL to 4 ± 0.4 ng/mL, P < 0.05). These changes were accompanied by decreases in LVM and LVMI.

Conclusions: We demonstrated that the serum 8-OHdG levels is increased in patients with Fabry cardiomyopathy (FC) and that successful management of FC with ERT is associated with a decrease in this oxidative stress marker. Serum 8-OHdG levels can be used not only as a noninvasive biomarker of oxidative stress in patients with FC but also an objective and quantitative parameter in the follow-up of patients during ERT.

Keywords: Cardiomyopathy; ERT; Fabry disease; Oxidative stress.

MeSH terms

8-Hydroxy-2'-Deoxyguanosine
Aged
Biomarkers / blood
Cardiomyopathies / blood
Cardiomyopathies / complications
Cardiomyopathies / diagnosis
Cardiomyopathies / drug therapy*
Case-Control Studies
Deoxyguanosine / analogs & derivatives*
Deoxyguanosine / blood
Enzyme Replacement Therapy*
Fabry Disease / blood
Fabry Disease / complications
Fabry Disease / diagnosis
Fabry Disease / drug therapy*
Female
Glycolipids / blood*
Humans
Male
Middle Aged
Monitoring, Physiologic
Oxidative Stress
Sphingolipids / blood*
Treatment Outcome
alpha-Galactosidase / therapeutic use*

Substances

Biomarkers
Glycolipids
Sphingolipids
globotriaosyl lysosphingolipid
8-Hydroxy-2'-Deoxyguanosine
alpha-Galactosidase
Deoxyguanosine