TY - JOUR
T1 - Prostaglandin H synthase and lipoxygenase mediated activation of xenobiotics in platelets
AU - Lim, K. M.
AU - Lee, J. Y.
AU - Kim, J. S.
AU - Chung, J. H.
PY - 2000
Y1 - 2000
N2 - To investigate the involvement of prostaglandin H synthase (PHS) and lipoxygenase (LPO) in the activation of xenobiotics in platelets, platelet sonicates were preincubated with α-naphthol. Protein covalent binding of α-naphthol was measured following addition of arachidonic acid. Protein covalent binding was increased in a dose-dependent manner until it plateaued at 500 μM arachidonic acid. Pretreatment by two inhibitors of PHS, aspirin and indomethacin, resulted in a dose-dependent inhibition of α-naphthol-induced covalent binding, confirming PHS involvement. In addition, pretreatment by a LPO inhibitor, nordihydroguaiaretic acid (NDGA), also prevented covalent binding substantially, showing that LPO may be an alternative pathway for xenobiotic activation in platelets. Furthermore, combined treatment of aspirin and NDGA almost abolished the increase of (α-naphthol-induced covalent binding, suggesting that PHS and LPO are both major pathways for xenobiotic activation in platelets.
AB - To investigate the involvement of prostaglandin H synthase (PHS) and lipoxygenase (LPO) in the activation of xenobiotics in platelets, platelet sonicates were preincubated with α-naphthol. Protein covalent binding of α-naphthol was measured following addition of arachidonic acid. Protein covalent binding was increased in a dose-dependent manner until it plateaued at 500 μM arachidonic acid. Pretreatment by two inhibitors of PHS, aspirin and indomethacin, resulted in a dose-dependent inhibition of α-naphthol-induced covalent binding, confirming PHS involvement. In addition, pretreatment by a LPO inhibitor, nordihydroguaiaretic acid (NDGA), also prevented covalent binding substantially, showing that LPO may be an alternative pathway for xenobiotic activation in platelets. Furthermore, combined treatment of aspirin and NDGA almost abolished the increase of (α-naphthol-induced covalent binding, suggesting that PHS and LPO are both major pathways for xenobiotic activation in platelets.
UR - http://www.scopus.com/inward/record.url?scp=0034465708&partnerID=8YFLogxK
M3 - Article
C2 - 10667392
AN - SCOPUS:0034465708
SN - 0065-2598
VL - 469
SP - 631
EP - 637
JO - Advances in Experimental Medicine and Biology
JF - Advances in Experimental Medicine and Biology
ER -