title: Assessment of atherosclerosis risk due to the homocysteine-asymmetric dimethylarginine-nitric oxide cascade in children taking antiepileptic drugs.
abstract: OBJECTIVE
  The aim of this study was to assess the atherogenicity risk of antiepileptics in children by investigating the cascade, "hyperhomocysteinemia (HHcy)→asymmetric dimethylarginine (ADMA) increase→nitric oxide (NO) decrease", which is thought to contribute to the developmental process of atherosclerosis.
  
  
  METHODS
  The participants included 53 epilepsy patients who received either valproic acid (VPA, n=26) or oxcarbazepine (OXC, n=27). Twenty-four healthy sex- and age-matched children served as controls. Fasting plasma total homocysteine (tHcy), ADMA and NO levels were measured.
  
  
  RESULTS
  The differences in Hcy, ADMA, NO, vitamin B(12) and folate levels between VPA, OXC and control groups were all insignificant (p>0.05 for all). In the patient group (VPA and OXC groups), 22.6% of the children (12/53) had tHcy levels above the normal cutoff (13.1μmol/l) for children and 17% of the children (9/53) had tHcy levels of greater than 15μmol/l which is accepted as the critical value for an increased atherosclerosis risk (p<0.05 for both). The difference in rate of HHcy between VPA and OXC groups was statistically insignificant (p>0.05, for both cut off levels of HHCy). There was a positive correlation of tHcy levels and antiepileptic drug treatment duration in the patient group (r=+0.276, p<0.05).
  
  
  CONCLUSIONS
  HHcy may develop in patients using OXC. Contrary to some previous publications, our data do not suggest that OXC is safer than VPA in terms of HHcy risk. Further prospective, large scale and longer term studies investigating all suggested pathways responsible for development of atherosclerosis due to HHcy should be conducted to define the exact mechanism responsible for AEDs related atherosclerosis.
authors.affiliation: Department of Pediatrics, Gazi University, TR-06450 Ankara, Turkey. hcemeksiz@gmail.com
authors.forename: Hamdi Cihan
authors.initials: HC
authors.lastname: Emeksiz
authors.forename: Ayse
authors.initials: A
authors.lastname: Serdaroglu
authors.forename: Gürsel
authors.initials: G
authors.lastname: Biberoglu
authors.forename: Ozlem
authors.initials: O
authors.lastname: Gulbahar
authors.forename: Ebru
authors.initials: E
authors.lastname: Arhan
authors.forename: Ali
authors.initials: A
authors.lastname: Cansu
authors.forename: Mustafa
authors.initials: M
authors.lastname: Arga
authors.forename: Alev
authors.initials: A
authors.lastname: Hasanoglu
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D050197:Atherosclerosis / Q000097:blood* / Q000139:chemically induced / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002220:Carbamazepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D000078330:Oxcarbazepine; D011446:Prospective Studies; D012307:Risk Factors; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D015415:Biomarkers; D006710:Homocysteine; D009569:Nitric Oxide; D002220:Carbamazepine; D014635:Valproic Acid; C018524:N,N-dimethylarginine; D001120:Arginine; D000078330:Oxcarbazepine