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Drug-induced pertubation of the aminothiol redox-status in patients with epilepsy: improvement by B-vitamins.
Epilepsy Res 2008; 82(1):1-6ER

Abstract

OBJECTIVES

Patients with epilepsy have excess morbidity and mortality due to ischemic cardiovascular disease. Many of these patients have elevated concentrations of plasma total homocysteine (Hcy), which is an acknowledged risk factor for cardiovascular disease, venous thromboembolic disease, foetal malformations and dementia. Hyperhomocysteinemia may have negative effects through mechanisms involving oxidative damage. In the present study, we have investigated the aminothiol redox-status in patients on antiepileptic drugs. Thereafter, in a subset of patients with elevated total Hcy, we evaluated the effect of B-vitamin therapy.

METHODS

In the first part of the study, 101 patients on antiepileptic drugs were compared with 101 matched healthy controls. The redox-species of Hcy, cysteine and cysteinylglycine, the major aminothiols in plasma, were analyzed by high-performance liquid chromatography (HPLC). Hyperhomocysteinemia was defined as fasting total Hcy above 12 micromol/L and/or post-methionine load concentrations above 38 micromol/L. In the second part of the study, 33 patients identified with hyperhomocysteinemia were supplemented with three B-vitamins for 30 days; folic acid (B9), pyridoxine (B6) and riboflavin (B2).

RESULTS

All redox-species of Hcy were significantly elevated in the patients, except the fasting concentrations of reduced Hcy (p=0.09). The reduced/total ratio of cysteine in fasting plasma was lower in the patients than in the controls: 5.20% vs. 6.19%, respectively (p=0.006). After 30 days of B-vitamin supplementation, the plasma concentrations of reduced, oxidized and protein-bound Hcy species were significantly lowered by 17%, 22% and 28%, respectively. The reduced/total ratio of cysteine rose from 4.9% to 7.9% (p=0.007).

CONCLUSIONS

Patients on antiepileptic drugs have abnormal aminothiol redox-status associated with hyperhomocysteinemia. This is similar to findings in patients with cardiovascular disease. B-vitamin supplementation partially corrects the abnormal aminothiol redox-status. Possibly, B-vitamin supplementation may be useful in drug-induced hyperhomocysteinemia.

Authors+Show Affiliations

Department of Medicine, Stavanger University Hospital, Stavanger, Norway. apeland@online.noNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18644700

Citation

Apeland, Terje, et al. "Drug-induced Pertubation of the Aminothiol Redox-status in Patients With Epilepsy: Improvement By B-vitamins." Epilepsy Research, vol. 82, no. 1, 2008, pp. 1-6.
Apeland T, Frøyland ES, Kristensen O, et al. Drug-induced pertubation of the aminothiol redox-status in patients with epilepsy: improvement by B-vitamins. Epilepsy Res. 2008;82(1):1-6.
Apeland, T., Frøyland, E. S., Kristensen, O., Strandjord, R. E., & Mansoor, M. A. (2008). Drug-induced pertubation of the aminothiol redox-status in patients with epilepsy: improvement by B-vitamins. Epilepsy Research, 82(1), pp. 1-6. doi:10.1016/j.eplepsyres.2008.06.003.
Apeland T, et al. Drug-induced Pertubation of the Aminothiol Redox-status in Patients With Epilepsy: Improvement By B-vitamins. Epilepsy Res. 2008;82(1):1-6. PubMed PMID: 18644700.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Drug-induced pertubation of the aminothiol redox-status in patients with epilepsy: improvement by B-vitamins. AU - Apeland,Terje, AU - Frøyland,Elin S, AU - Kristensen,Ole, AU - Strandjord,Roald E, AU - Mansoor,Mohammad A, Y1 - 2008/07/21/ PY - 2008/02/25/received PY - 2008/05/25/revised PY - 2008/06/12/accepted PY - 2008/7/23/pubmed PY - 2009/4/14/medline PY - 2008/7/23/entrez SP - 1 EP - 6 JF - Epilepsy research JO - Epilepsy Res. VL - 82 IS - 1 N2 - OBJECTIVES: Patients with epilepsy have excess morbidity and mortality due to ischemic cardiovascular disease. Many of these patients have elevated concentrations of plasma total homocysteine (Hcy), which is an acknowledged risk factor for cardiovascular disease, venous thromboembolic disease, foetal malformations and dementia. Hyperhomocysteinemia may have negative effects through mechanisms involving oxidative damage. In the present study, we have investigated the aminothiol redox-status in patients on antiepileptic drugs. Thereafter, in a subset of patients with elevated total Hcy, we evaluated the effect of B-vitamin therapy. METHODS: In the first part of the study, 101 patients on antiepileptic drugs were compared with 101 matched healthy controls. The redox-species of Hcy, cysteine and cysteinylglycine, the major aminothiols in plasma, were analyzed by high-performance liquid chromatography (HPLC). Hyperhomocysteinemia was defined as fasting total Hcy above 12 micromol/L and/or post-methionine load concentrations above 38 micromol/L. In the second part of the study, 33 patients identified with hyperhomocysteinemia were supplemented with three B-vitamins for 30 days; folic acid (B9), pyridoxine (B6) and riboflavin (B2). RESULTS: All redox-species of Hcy were significantly elevated in the patients, except the fasting concentrations of reduced Hcy (p=0.09). The reduced/total ratio of cysteine in fasting plasma was lower in the patients than in the controls: 5.20% vs. 6.19%, respectively (p=0.006). After 30 days of B-vitamin supplementation, the plasma concentrations of reduced, oxidized and protein-bound Hcy species were significantly lowered by 17%, 22% and 28%, respectively. The reduced/total ratio of cysteine rose from 4.9% to 7.9% (p=0.007). CONCLUSIONS: Patients on antiepileptic drugs have abnormal aminothiol redox-status associated with hyperhomocysteinemia. This is similar to findings in patients with cardiovascular disease. B-vitamin supplementation partially corrects the abnormal aminothiol redox-status. Possibly, B-vitamin supplementation may be useful in drug-induced hyperhomocysteinemia. SN - 1872-6844 UR - https://www.unboundmedicine.com/medline/citation/18644700/Drug_induced_pertubation_of_the_aminothiol_redox_status_in_patients_with_epilepsy:_improvement_by_B_vitamins_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0920-1211(08)00168-X DB - PRIME DP - Unbound Medicine ER -