Acta Vet. Brno 2010, 79: 443-448

https://doi.org/10.2754/avb201079030443

Modulation of Tularemia Disease Progress by the Bisquaternary Pyridinium Oxime HI-6

Miroslav Pohanka1,2, Oto Pavliš3,4, Jiří Pikula5, František Treml6, Kamil Kuca2,7

1Centre of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic
2Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic
3Centre of Biological Defence, Těchonín, Czech Republic
4Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic
5Department of Veterinary Ecology and Environmental Protection, Faculty of Veterinary Hygiene and Ecology
6Department of Infectious Diseases and Epizootiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences Brno, Czech Republic
7Centre of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic

Cholinesterase reactivator HI-6 is a drug commonly used to treat individuals exposed to nerve agents. Recent experiments proved HI-6 impact on parasympathetic response and impact on the nervus vagus associated cholinergic anti-inflammatory pathway is hypothesized here. The modulation effect of HI-6 was studied on BALB/c mice infected with Francisella tularensis, the bacteria causing tularemia. Cultivation test in vitro confirmed weak bacteriostatic effects of HI-6. Results in experiments revealed intriguing effect differences resulting from HI-6 administration to mice. While the HI-6 dose of 7 mg per animal (pro toto) had no significant effects on infection progress, lower dose of 8 μg of HI-6 pro toto reduced mice mortality caused by tularemia infection compared to control group of mice infected only with F. tularensis (survival curves were compared by the logrank test, chi square = 4.335, df = 1, P = 0.0373). The effect observed in mice exceeded the effect provided in vitro on bacterial cultures. Though the exact molecular mechanism of HI-6 modulation during infection should be investigated, HI-6 is seems to be suitable as immunomodulans.

References

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