Human Plasma Carboxyl Esterase-catalyzed Triolein Hydrolysis

Shirai, Kohji; Ohsawa, Ikuko; Ishikawa, Yoh; Saitō, Yasushi; Yoshida, Sho

doi:10.5551/jat1973.13.4_939

Cited by 4 publications

(4 citation statements)

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“…However, more recent studies consistently found that carboxylesterase activity in human plasma or serum is low, whereas it is high in rodent serum 12,32‐40 . Nevertheless, significant carboxylester‐hydrolyzing enzyme activity is present in human serum or plasma, both in neonates and adults, 12,33‐35 which is also demonstrated by the current study.…”

Section: Discussionsupporting

confidence: 80%

Hydrolytic biotransformation of the bumetanide ester prodrug DIMAEB to bumetanide by esterases in neonatal human and rat serum and neonatal rat brain—A new treatment strategy for neonatal seizures?

Theilmann¹,

Brandt²,

Bohnhorst

et al. 2020

Epilepsia

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ObjectivesThe loop diuretic bumetanide has been proposed previously as an adjunct treatment for neonatal seizures because bumetanide is thought to potentiate the action of γ‐aminobutyric acid (GABA)ergic drugs such as phenobarbital by preventing abnormal intracellular accumulation of chloride and the subsequent "GABA shift." However, a clinical trial in neonates failed to demonstrate such a synergistic effect of bumetanide, most likely because this drug only poorly penetrates into the brain. This prompted us to develop lipophilic prodrugs of bumetanide, such as the N,N‐dimethylaminoethyl ester of bumetanide (DIMAEB), which rapidly enter the brain where they are hydrolyzed by esterases to the parent compound, as demonstrated previously by us in adult rodents. However, it is not known whether esterase activity in neonates is sufficient to hydrolyze ester prodrugs such as DIMAEB.MethodsIn the present study, we examined whether esterases in neonatal serum of healthy term infants are capable of hydrolyzing DIMAEB to bumetanide and whether this activity is different from the serum of adults. Furthermore, to extrapolate the findings to brain tissue, we performed experiments with brain tissue and serum of neonatal and adult rats.ResultsSerum from 1‐ to 2‐day‐old infants was capable of hydrolyzing DIMAEB to bumetanide at a rate similar to that of serum from adult individuals. Similarly, serum and brain tissue of neonatal rats rapidly hydrolyzed DIMAEB to bumetanide.SignificanceThese data provide a prerequisite for further evaluating the potential of bumetanide prodrugs as add‐on therapy to phenobarbital and other antiseizure drugs as a new strategy for improving pharmacotherapy of neonatal seizures.

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Section: Discussionsupporting

confidence: 80%

Hydrolytic biotransformation of the bumetanide ester prodrug DIMAEB to bumetanide by esterases in neonatal human and rat serum and neonatal rat brain—A new treatment strategy for neonatal seizures?

Theilmann¹,

Brandt²,

Bohnhorst

et al. 2020

Epilepsia

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“…There are multiple forms of CaE in the liver (Junge and Krisch, 1975;Morgan et al, 1994) and plasma (Tsujita and Okuda, 1983). CaEs are also substratespecific (Tsujita and Okuda, 1983;Stem et al, 1985a,b;Fonnum et al, 1985;Shirai et al, 1985). In the majority of our experiments, we have defined CaE using PNPA as a substrate.…”

Section: Discussionmentioning

confidence: 98%

Tissue-Specific Effects of Chlorpyrifos on Carboxylesterase and Cholinesterase Activity in Adult Rats: An in Vitro and in Vivo Comparison

et al. 1997

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“…This did not occur with 24-hr incubation (Table 4). We believe this indicates a natural inhibitor of human BuChE, a phenomenon known for other human plasma enzymes (Shirai et al, 1985;Subbaiah et al, 1992).…”

Section: Discussionmentioning

confidence: 67%

Inhibition of Human Plasma and Serum Butyrylcholinesterase (EC 3.1.1.8) by α-Chaconine and α-Solanine

et al. 1996

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The purpose of these experiments was to determine the reversibility of a-chaconine and a-solanine inhibition of human plasma butyrylcholinesterase (BuChE). For the substrate a-naphthylacetate, optimal assay conditions were 0.50 M sodium phosphate buffer and a substrate concentration of 3-5 X 10~4 M. Dibucaine (1 X 10~5 M) indicated the usual phenotype for all subjects; achaconine and a-solanine at 2.88 X 10~6 M inhibited BuChE about 70 and 50%, respectively. One-and 24-hr incubations at 1 X 10~! M with a-chaconine, a-solanine, paraoxon, eserine, and ethanol yielded reversible inhibition with dilution except for paraoxon. Twenty-four-hour dialyses of incubations showed no inhibition except for paraoxon. PAGE enzyme activity gels of 1-and 24-hr incubations also showed no inhibition except for paraoxon. aChaconine and a-solanine are reversible inhibitors of human butyrylcholinesterase. At estimated tissue levels, a-chaconine, a-solanine, and solanidine inhibited BuChE 10-86%. In assays which combined a-chaconine, a-solanine, and solanidine, inhibition of BuChE was less than additive. No inhibition of albumin a-naphthylacetate esterase (an arylesterase) was noted with any inhibitor. The importance of these data to adverse toxicological effects of potato alkaloids is diSCUSSed. C 1996 SodMy of Toxicology.Potatoes, consumed by humans for at least 2000 years (Spoerke, 1994;Ugent, 1970), contain the steroidal alkaloids, a-chaconine, a-solanine, and solanidine. The toxicology of these known butyryl-and acetylcholinesterase inhibitors (Harris and Whittaker, 1962;Orgell, 1963) has been reviewed

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Human Plasma Carboxyl Esterase-catalyzed Triolein Hydrolysis

Cited by 4 publications

References 0 publications

Hydrolytic biotransformation of the bumetanide ester prodrug DIMAEB to bumetanide by esterases in neonatal human and rat serum and neonatal rat brain—A new treatment strategy for neonatal seizures?

Hydrolytic biotransformation of the bumetanide ester prodrug DIMAEB to bumetanide by esterases in neonatal human and rat serum and neonatal rat brain—A new treatment strategy for neonatal seizures?

Tissue-Specific Effects of Chlorpyrifos on Carboxylesterase and Cholinesterase Activity in Adult Rats: An in Vitro and in Vivo Comparison

Inhibition of Human Plasma and Serum Butyrylcholinesterase (EC 3.1.1.8) by α-Chaconine and α-Solanine

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