title: Role of free radicals and platelet-activating factor in the genesis of intestinal motor disturbances induced by Escherichia coli endotoxins in rats.
abstract: The effects of IV administration of Escherichia coli endotoxin on intestinal myoelectric activity was investigated in conscious fasted rats chronically implanted with nichrome electrodes in the duodenojejunum. These effects were compared with those of platelet-activating factor and were evaluated in animals pretreated with a specific platelet-activating factor antagonist, BN 52021, indomethacin, a selective prostaglandin E2 antagonist, SC 19220, and several free radical scavengers. Intravenous administration of endotoxin (E. coli S.O111:B4) at a dose of 50 micrograms/kg suppressed the migrating myoelectric complexes, which were replaced by continuous rhythmic clusters of rapidly propagated spike bursts for 114.7 +/- 19.9 minutes. Intraperitoneal platelet-activating factor (25 micrograms/kg) also inhibited the migrating myoelectric complex pattern for 146.1 +/- 24.1 minutes. Previous IV administration of BN 52021 (50 mg/kg-1) abolished the motor alterations induced by platelet-activating factor and significantly reduced to 43.1 +/- 12.2 minutes those induced by endotoxin (P less than 0.01). Indomethacin (10 mg/kg IP), injected before endotoxin or platelet-activating factor, also significantly reduced the duration of migrating myoelectric complex inhibition to 45.6 +/- 7.8 and 47.7 +/- 8.3 minutes, respectively (P less than 0.01). SC 19220 significantly reduced the effects of platelet-activating factor from 151.8 +/- 26.4 to 67.4 +/- 14.7 min (P less than 0.01). Superoxide dismutase (15,000 U/kg IV) injected before either endotoxin or platelet-activating factor shortened the migrating myoelectric complex inhibition to 45.7 +/- 9.9 and 72.9 +/- 10.4 minutes, respectively (P less than 0.01). Allopurinol and dimethylsulfoxide administered orally at 50 mg/kg 1 hour before endotoxin reduced the migrating myoelectric complex inhibition to 42.5 +/- 6.5 and 38.2 +/- 6.4 minutes, respectively (P less than 0.01). They also reduced platelet-activating factor-induced intestinal myoelectric alterations to 68.5 +/- 10.6 and 31.7 +/- 6.1 minutes, respectively (P less than 0.01). It is concluded that endogenous release of platelet-activating factor is partly responsible for the intestinal motor alterations induced by endotoxin, these effects being also mediated through the release of prostaglandins and free radicals. However, prostaglandins, as well as free radicals, appear to be partly involved in the platelet-activating factor-induced action of E. coli endotoxin on intestinal motility.
authors.affiliation: Department of Pharmacology-Toxicology, Institut National de la Recherche Agronomique, Toulouse, France.
authors.forename: L
authors.initials: L
authors.lastname: Pons
authors.forename: M T
authors.initials: MT
authors.lastname: Droy-Lefaix
authors.forename: P
authors.initials: P
authors.lastname: Braquet
authors.forename: L
authors.initials: L
authors.lastname: Bueno
mesh_terms: D000818:Animals; D003967:Diarrhea / Q000139:chemically induced / Q000503:physiopathology; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000494:pharmacology; D004224:Diterpenes; D004576:Electromyography; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D016166:Free Radical Scavengers; D005609:Free Radicals; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D046934:Ginkgolides; D007213:Indomethacin / Q000494:pharmacology; D007421:Intestine, Small / Q000187:drug effects / Q000503:physiopathology; D007783:Lactones / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004224:Diterpenes; D004731:Endotoxins; D016166:Free Radical Scavengers; D005609:Free Radicals; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; C044101:endotoxin, Escherichia coli; C045856:ginkgolide B; D007213:Indomethacin