Inhibition of cyclooxygenase activity, platelet aggregation and thromboxane B2 production by two environmental toxicants: m- and o-cresol.
Cresol is a well-known environmental pollutant, toluene metabolite, uremic toxicant and accidental poisoning product. Formocresol, a preparation of formalin and cresol, is also used as a root canal medicament and for pulpotomy of primary teeth. However, little is known about its effect on cardiovascular system. In this study, m-cresol inhibited the AA-induced platelet aggregation by 43-97% at concentrations ranging from 0.25 to 1 mM. Collagen-induced platelet aggregation was also inhibited by 0.25-1 mM of m-cresol by 47-98%. Accordingly, o-cresol (0.1-0.5 mM) also inhibited the AA-induced platelet aggregation by 46-96% and the collagen-induced platelet aggregation by 35-88% at concentrations of 0.1-1 mM. AA- and collagen-induced platelet thromboxane B(2) (TXB(2)) production was inhibited by even 0.1 mM of m-cresol with 88 and 54% of inhibition, respectively. The o-cresol (0.1 mM) also inhibited the AA- and collagen-induced platelet TXB(2) production with 91 and 97% respectively. Although m- and o-cresol (<1 mM) showed little effect on thrombin-induced platelet aggregation, they effectively inhibited the thrombin-induced platelet TXB(2) production. The m-cresol (2 and 5 mM) inhibited the COX-1 activity by 55-99%, but showed little effect on COX-2 enzyme activity. Moreover, o-cresol (0.5 and 1 mM) inhibited the COX-1 activity by 40-95%. COX-2 enzyme activity was inhibited by 68% at a concentration of 5 mM o-cresol. These results indicate that acute cresol-poisoning, direct root canal medication with formocresol or long-term occupational exposure to cresol and toluene may potentially suppress blood clot formation and lead to tissue hemorrhage via inhibition of platelet aggregation, TXB(2) production and COX enzyme activity.
Chan
Chiu-Po
CP
Department of Dentistry, Chang-Gung Memorial Hospital, Taipei, Taiwan.
Yuan-Soon
Ho
H
Wang
Ying-Jen
YJ
Lan
Wan-Hong
WH
Chen
Lin-I
LI
Chen
Yi-Jane
YJ
Lin
Bor-Ru
BR
Chang
Mei-Chi
MC
Jeng
Jiiang-Huei
JH
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D003408:Cresols / Q000633:toxicity*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000633:toxicity*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011817:Rabbits; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D003408:Cresols; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004785:Environmental Pollutants; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C042041:3-cresol; C034047:2-cresol