title: Intravenous pyruvic acid application in minipigs partially protects acetylcholine-esteratic but not butyrylcholine-esteratic activity in plasma from inhibition by paraoxon.
abstract: Intoxications with organophosphorus compounds such as paraoxon (POX) are frequent. Oximes are the only enzyme reactivators clinically available. In vitro and in vivo studies have shown that l-lactate reduces the inhibition of plasma acetylcholine-esteratic activity (AChEA) (in vitro and in vivo) and plasma butyrylcholine-esteratic activity (BChEA) (at least in vitro and possibly in vivo) by POX. However, a short infusion of 10 g of lactate was unable to elevate the plasma lactate level for >3 h. In this study we tested a substance related to l-lactate, i.e. pyruvic acid. The purpose of this animal experimental study (female minipigs with historical control group) was to determine in vivo whether intravenous (i.v.) pyruvic acid application under normoxic/normocapnic/normohydrogenaemic conditions is able to elevate blood lactate levels and whether it is able to protect AChEA and BChEA from POX inhibition. Animals were anaesthetized, intubated and mechanically ventilated. Each received 1 mg kg(-1) body wt. of POX in 50 ml of saline over 50 min and 10 g (ca. 0.5 g kg(-1) body wt.) of i.v. pyruvic acid in 50 ml of saline over 50 min. They were compared with a historical control group of six animals that received only 1 mg kg(-1) body wt. of POX in 50 ml of saline over 50 min. In central venous blood measurements of plasma AChEA and BChEA, the measurements were performed before (baseline), immediately after POX (50 min after start) and 110, 170, 230, 290, 530 and 1010 min after the start of infusion. A 10 g aliquot of i.v. pyruvic acid had a statistically significant protective effect in vivo on AChEA but not on BChE activity. Further study of the in vivo effects of pyruvic acid and l-lactate after paraoxon intoxication and a formal comparison with standard oxime therapy seems warranted. Also, a combination therapy with l-lactate and pyruvic acid in vivo should be investigated.
authors.affiliation: United Arab Emirates University, Faculty of Medicine and Health Sciences, Department of Pharmacology, Al Ain, United Arab Emirates. georg.petroianu@uaeu.ac.ae
authors.forename: Georg A
authors.initials: GA
authors.lastname: Petroianu
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ewald
authors.forename: Caroline
authors.initials: C
authors.lastname: Thyes
authors.forename: Anke
authors.initials: A
authors.lastname: Missler
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Maleck
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood*; D000818:Animals; D002091:Butyrylcholinesterase / Q000097:blood*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000494:pharmacology*; D004336:Drug Antagonism; D005260:Female; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000097:blood; D010261:Paraoxon / Q000633:toxicity*; D019289:Pyruvic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D013379:Substrate Specificity; D013552:Swine; D013556:Swine, Miniature
chemical_list: D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D019344:Lactic Acid; D019289:Pyruvic Acid; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D010261:Paraoxon