The toxicological significance of paraoxon deethylation

Detoxication of paraoxon by rat liver homogenate and serum carboxylesterases and A-esterases*

“…The toxic effects apparently correlate inversely to the detoxication capacity in the liver and the general circulation. Although other PO detoxication pathways have been reported (23,24), CbxE and A-esterases appear to be the most important. The in vivo experiments here confirmed the importance of the hepatic and plasma CbxE in protecting brain AChE from organophosphate inhibition shortly (within 15 min) after a high dosage exposure to the parent insecticide (Table 1).…”

Metabolism of parathion in perfused whole pig livers

“…In the blood, the importance of deethylating enzymes is more obscure. Even though the blood has a greater chance to deethylate paraoxon than parathion on the way to the liver, the deethylation:dearyla tion ratios are similar for both compounds in the blood (Appleton and Nakatsugawa, 1977). It may be that the toxicological significance of blood esterase lies in the fact that paraoxon blood levels are low, there by alleviating the necessity for a higher deethylation:dearylation mecha nism to detoxify paraoxon.…”

“…gated (Appleton and Nakatsugawa, 1977;Fuhremann et al, 1974;Gaines et al, 1966;Ku and Dahm, 1973;Lichtenstein et al, 1973;Miyata and Matsumura, 1972;Nakatsugawa and Dahm, 1967;Nakatsugawa et al, 1968Nakatsugawa et al, , 1969Neal, 1967a,b;Neal and DuBois, 1965;Pankaskie et al, 1952;Whitehouse and Ecobichon, 1975) and reviewed (Schoenig, 1975). These studies have revealed an ^ vivo metabolic manipulation of parathion via two pathways (Figure 1).…”

“…More than one enzyme is involved with desulfuration of parathion (Nakatsugawa et al, 1969). One of the principle enzymes is glutathione-SH transferase (Appleton and Nakatsugawa, 1977).…”

“…Other tissues (lung and blood > kidney > spleen, pancreas, heart, muscle, brain, small intestine, large intestine) are able to induce paraoxon degrada tion no more than 10% that of the liver (Ku and Dahm, 1973;Nakatsugawa et al, 1969;Appleton and Nakatsugawa, 1977;Neal, 1967a). Phosphatase action vivo is a cooperative event of a heterogeneous population of several enzymes with a collectively different ^ vivo sig nificance (Appleton and Nakatsugawa, 1977), and physical isolation of these enzymes in cells may not allow all to participate in paraoxon metabolism ^ vivo. In the blood, the importance of deethylating enzymes is more obscure.…”