title: Aspirin insensitive thromboxane generation is associated with oxidative stress in type 2 diabetes mellitus.
abstract: BACKGROUND
  Aspirin (ASA) irreversibly inhibits platelet cyclooxygenase-1 (COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on platelet activation, thromboxane generation, oxidative stress and anti-oxidant biomarkers was studied in type 2 diabetes mellitus (DM).
  
  
  METHODS
  Baseline and post-ASA samples (100/325 mg x 7 days) were obtained from 75 DM patients and 86 healthy controls for urinary 11-dehydro-thromboxane B2 (11 dhTxB2), 8-iso-prostaglandin-F2α (8-isoPGF2α) and serum sP-Selectin, nitrite (NO(2)(-)), nitrate (NO(3)(-)) and paraoxonase 1 (PON1) activity.
  
  
  RESULTS
  Compared to baseline controls, baseline DM had higher mean levels of 11 dhTxB2 (3,665 ± 2,465 vs 2,450 ± 1,572 pg/mg creatinine, p=0.002), 8-isoPGF2α (1,457 ± 543 vs 1,009 ± 412 pg/mg creatinine, p<0.0001), NO(2)(-) (11.8 ± 7.3 vs 4.8 ± 5.3 μM, p<0.0001), NO(3)(-) (50.4 ± 39.3 vs 20.9 ± 16.7 μM, p<0.0001) and sP-Selectin (120.8 ± 56.7 vs 93.0 ± 26.1 ng/mL, p=0.02), and the same held for post-ASA levels (p<0.0001). ASA demonstrated no effect on 8-isoPGF2α, NO(2)(-), NO(3)(-), sP-Selectin or PON1 activity in either DM or controls. Post ASA inhibition of urinary 11 dhTxB2 was 71.5% in DM and 75.1% in controls. There were twice as many ASA poor responders in DM than in controls (14.8% and 8.4%) based on systemic thromboxane reduction. Urinary 8-isoPGF2α excretion was greater in DM ASA poor responders than good responders (p<0.009).
  
  
  CONCLUSIONS
  This suggests that oxidative stress may maintain platelet function irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources.
authors.affiliation: Queen Mary University of London, William Harvey Research Institute, Centre for Sports and Exercise Medicine, Mile End Hospital, London, UK. paxmes@aol.com
authors.forename: Paul R J
authors.initials: PR
authors.lastname: Ames
authors.forename: Joana R
authors.initials: JR
authors.lastname: Batuca
authors.forename: Ivana J
authors.initials: IJ
authors.lastname: Muncy
authors.forename: Ignacio Garcia
authors.initials: IG
authors.lastname: De La Torre
authors.forename: Sara
authors.initials: S
authors.lastname: Pascoe-Gonzales
authors.forename: K
authors.initials: K
authors.lastname: Guyer
authors.forename: E
authors.initials: E
authors.lastname: Matsuura
authors.forename: Luis R
authors.initials: LR
authors.lastname: Lopez
mesh_terms: D000284:Administration, Oral; D000975:Antioxidants / Q000378:metabolism*; D001241:Aspirin / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D013929:Thromboxane B2 / Q000652:urine*
chemical_list: D000975:Antioxidants; D013929:Thromboxane B2; D001241:Aspirin