TY - JOUR
T1 - The effect of 2-(o-Cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide on tissue cholinesterase and carboxylesterase activities of the rat
AU - Jimmerson, V. R.
AU - Shih, T. M.
AU - Maxwell, D. M.
AU - Kaminskis, A.
AU - Mailman, R. B.
PY - 1989/10
Y1 - 1989/10
N2 - The dose-response (0.1 to 1000 mg/kg sc) effects of 2-(o-cresyl)-4H-l:3:2-benzodioxaphosphorin-2-oxide (CBDP; a melabolite of the organophosphorus compound tri-o-cresylphosphare on total cholinesterase (ChE) and carboxylesterase (CaE) activities in tissues from the rat were examined. Doses of CBDP greater than 1.0 mg/kg inhibited CaE activity maximally (>99%) in plasma and lung, two important sites for detoxification of organophosphorus toxicants. A biphasic dose-dependent inhibition of ChE activity was seen in all tissues; the ED5O values showed a difference of two orders of magnitude between the first and the second phases of the dose-response curves. CBDP inhibited the blood esterases in the order plasma CaE {black right-pointing small triangle} plasma ChE {black right-pointing small triangle} red blood cell (RBC) ChE. The biphasic dose-response curve and preferential inhibition of the blood esterases may reflect the inhibition of butyryicholinesterase in preference to acetylcholinesterase in these tissues. At doses of CBDP below 1.0 mg/kg, plasma, RBC, and brain regional ChE activities were inhibited by less than 10%, whereas at doses above 2.0 mg/kg, ChE activities were inhibited substantially (up to 80% in plasma, up to 60% in RBC, and greater than 90% in brain regions). On the basis of these results, a dose of CBDP between 1.0 and 2.0 mg/kg should prove useful as a pretreatment for studies of OP toxicity in the rat.
AB - The dose-response (0.1 to 1000 mg/kg sc) effects of 2-(o-cresyl)-4H-l:3:2-benzodioxaphosphorin-2-oxide (CBDP; a melabolite of the organophosphorus compound tri-o-cresylphosphare on total cholinesterase (ChE) and carboxylesterase (CaE) activities in tissues from the rat were examined. Doses of CBDP greater than 1.0 mg/kg inhibited CaE activity maximally (>99%) in plasma and lung, two important sites for detoxification of organophosphorus toxicants. A biphasic dose-dependent inhibition of ChE activity was seen in all tissues; the ED5O values showed a difference of two orders of magnitude between the first and the second phases of the dose-response curves. CBDP inhibited the blood esterases in the order plasma CaE {black right-pointing small triangle} plasma ChE {black right-pointing small triangle} red blood cell (RBC) ChE. The biphasic dose-response curve and preferential inhibition of the blood esterases may reflect the inhibition of butyryicholinesterase in preference to acetylcholinesterase in these tissues. At doses of CBDP below 1.0 mg/kg, plasma, RBC, and brain regional ChE activities were inhibited by less than 10%, whereas at doses above 2.0 mg/kg, ChE activities were inhibited substantially (up to 80% in plasma, up to 60% in RBC, and greater than 90% in brain regions). On the basis of these results, a dose of CBDP between 1.0 and 2.0 mg/kg should prove useful as a pretreatment for studies of OP toxicity in the rat.
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U2 - 10.1093/toxsci/13.3.568
DO - 10.1093/toxsci/13.3.568
M3 - Article
C2 - 2612789
AN - SCOPUS:77957177643
SN - 1096-6080
VL - 13
SP - 568
EP - 575
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 3
ER -