title: Effects of sublethal exposure of European brown hares to paraoxon on the course of tularemia.
abstract: OBJECTIVE
  The causative agent of tularemia Francisella tularensis is highly infectious and lagomorphs are important reservoirs and a source of human disease. The aim of the present study was to test the hypothesis that sublethal exposure to pesticides increases the susceptibility of hares to F. tularensis and modulates the course of the infection.
  
  
  METHODS
  Experimental hares were allocated to a) control, b) paraoxon-treated, c) F. tularensis-treated, and d) paraoxon-and-F. tularensis-treated groups of five specimens on a random basis and subcutaneously inoculated with a wild F. tularensis subsp. holarctica strain (a single dose of 9 × 108 CFU pro toto) and/or injected a sublethal dose of paraoxon (100 μg/kg). Group differences were evaluated using survival curves, oxidative stress responses as well as caspase-3 and acetylcholinesterase activities in whole blood samples collected on day 2 post exposure.
  
  
  RESULTS
  The paraoxon-and-F. tularensis-treated group showed a rapid onset of clinical signs and all deaths occurred on days 2 and 3 post exposure. F. tularensis-inoculated hares survived from 3 to 10 days, while only one hare died on day 12 in the paraoxon-treated group. Survival curves in the three exposed groups were significantly different from the control and median survival in F. tularensis-inoculated and paraoxon-and-F. tularensis-treated hares amounted to 7 and 2 days, respectively. Compared with controls, significant responses included an eight- and seven-fold activation of caspase-3 in F. tularensis-inoculated and paraoxon-and-F. tularensis-treated hares, respectively, and a 1.5-fold decrease of blood acetylcholinesterase activities in the paraoxon-treated and paraoxon-and-F. tularensis-treated groups. There was a 1.3- to 1.4-fold decrease of the ferric reducing antioxidant power in blood of F. tularensis-inoculated hares and the paraoxon-and-F. tularensis-treated group, respectively. The blood lipid peroxidation levels were of no differences among the four experimental groups.
  
  
  CONCLUSIONS
  Results of this study can help understand the pathogenesis of tularemia and mortality of hares in agricultural habitats. Use of anticholinesterase agents in agriculture can pose a threat of infectious disease outbreaks and higher mortality in wildlife populations.
authors.affiliation: Department of Veterinary Ecology and Environmental Protection, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Bandouchova
authors.forename: Miroslav
authors.initials: M
authors.lastname: Pohanka
authors.forename: Jiri
authors.initials: J
authors.lastname: Kral
authors.forename: Karel
authors.initials: K
authors.lastname: Ondracek
authors.forename: Jitka
authors.initials: J
authors.lastname: Osickova
authors.forename: Veronika
authors.initials: V
authors.lastname: Damkova
authors.forename: Frantisek
authors.initials: F
authors.lastname: Vitula
authors.forename: Frantisek
authors.initials: F
authors.lastname: Treml
authors.forename: Jiri
authors.initials: J
authors.lastname: Pikula
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D053148:Caspase 3 / Q000097:blood / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D004197:Disease Reservoirs; D004781:Environmental Exposure; D005604:Francisella tularensis / Q000472:pathogenicity / Q000502:physiology; D034621:Hares; D007306:Insecticides / Q000633:toxicity; D008297:Male; D010261:Paraoxon / Q000633:toxicity*; D011897:Random Allocation; D016019:Survival Analysis; D014406:Tularemia / Q000097:blood / Q000401:mortality / Q000473:pathology*
chemical_list: D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D000110:Acetylcholinesterase; D053148:Caspase 3; D010261:Paraoxon