Email this article 
Combined Pharmacological Correction of Experimental Frostbite
- Authors: 1, 1, 1, 1, 1, 1, 1
-
Affiliations:
- Kursk state Medical University, Kursk, Russian Federation
- Issue: Vol 6, No 1 (2013)
- Pages: 45-50
- Section: Original articles
- URL: https://vestnik-surgery.com/journal/article/view/29
- DOI: https://doi.org/10.18499/2070-478X-2013-6-1-45-50
- ID: 29
Cite item
Full Text
Abstract
Relevance Increased knowledge of the pathogenesis of frostbite and new pharmacological agents make it possible to improve the treatment results of local cold injury. This can be achieved, in particular, through the introduction of drug combination - the selective agonist of the delta-opioid receptors (DSLET) and the serotonergic agent (serotonin adipinate) which possesses analgesic, immunomodulatory, antioxidant and anti-inflammatory activity.
The purpose of the study To investigate the effect of combined pharmacological treatment by DSLET and serotonin adipinate in experimental local frostbite.
Materials and methods The study was conducted on 200 male Wistar rats. The local frostbite was inflicted with a preliminary cooled in liquid nitrogen metal plummet size 3.5-3.0 cm pressing against the shaved skin of the back during 3 min. Alongside with the standard antibiotic therapy (control) animals of the experimental groups were treated DSLET (10 mkg/kg intra-peritoneally (IP), serotonin adipinate (4.5 mg/kg IP) or its combination in indicated doses. Using the method of laser Doppler flowmetry the level of microcirculation was assessed as well as the biochemical changes in serum (malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), superoxide dismutase (SOD), catalase) in all animals at 1, 3, 7 and 14 days after cold injury.
Results and their discussion The model of local frostbite in control group resulted in reduction of microcirculation in necrosis boundary area at 1, 3, 7 and 14 days compared to the intact animals. The local frostbite injury induced oxidative stress and inflammation that were confirmed by typical dynamics of serum biochemical markers of non-treated rats while the significant increase the concentration of MDA, IL-6, TNF-α and decrease SOD activity were recognized. Also compensatory enhancement of catalase activity – one of the major antioxidant enzymes was observed. As well additional administration of drug combination DSLET (10 mkg/kg) with serotonin adipinate (4.5 mg/kg) to antibacterial treatment by cefotaxime in dose 0.085 g/kg increased the microcirculation by 27.2% compared to the non-treated group (р<0.05) at day 14 after damage due to frostbite injury in rats. A curative beneficial effect caused by combined pharmacological treatment of local frostbite was also confirmed by decrease of MDA concentration and pro-inflammatory cytokines IL-6 level at 1, 3, 5 and 7 days and by enhance of catalase and SOD activities at day 7 and 14 following experimentally induced frostbite.
Conclusion Compared to monotherapy, combined usage of DSLET and serotonin adipinate provides a better pharmacological treatment efficiency in experimental model of local frostbite.
About the authors
Kursk state Medical University, Kursk, Russian Federation
Author for correspondence.
Email: kurskmed@mail.ru
Rector of Kursk State Medical University, Doctor of Medical Sciences, Professor, Head of Surgical Pathology Department of Postgraduate Education Division of Kursk State Medical University
Kursk state Medical University, Kursk, Russian Federation
Email: eartyushkova@mail.ru
Doctor of Biological Sciences, Director of Scientific Research Institute of Environmental Medicine of Kursk State Medical University
Kursk state Medical University, Kursk, Russian Federation
Email: vladimirshef2011@mail.ru
Doctor of Medical Sciences, Professor of Surgical Pathology Department of Postgraduate Education Division of Kursk State Medical University
Kursk state Medical University, Kursk, Russian Federation
Email: levan77@yandex.ru
Candidate of Medical Sciences, Assistant Professor of Surgical Pathology Department of Postgraduate Education Division of Kursk State Medical University
Kursk state Medical University, Kursk, Russian Federation
Email: moni-1@yandex.ru
Candidate of Medical Sciences, Assosiate Professor of Surgical Pathology Department
of Postgraduate Education Division of Kursk State Medical University
Kursk state Medical University, Kursk, Russian Federation
Email: alessio18@mail.ru
Postgraduate student of Surgical Pathology Department of Postgraduate Education Division of Kursk State Medical University
Kursk state Medical University, Kursk, Russian Federation
Email: savens@mail.ru
Candidate of Medical Sciences, Researcher of Scientific Research Institute of Environmental Medicine of Kursk State Medical University
References
- Artiushkova E.B., Pashkov D.V., Tsokolaeva Z.I., i dr. Sravnitel'naya ocenka angiogennogo ehffekta L-arginina i sosudistogo ehndotelial'nogo faktora rosta (vegf) pri ehksperimental'noj ishemii konechnosti. [Comparative evaluation of the angiogenic effect of L-arginine and vascular endothelial growth factor (VegF) in experimental ischemia of the limb.] Rossiiskii medikobiologicheskii vestnik im. akademika I.P. Pavlova, 2009; 1: 46-52.
- Boiko V.V., Milovidova A.E., Ianovskaia L.G. i dr. Izuchenie morfologicheskih osobennostej v tkanyah ehksperimental'nyh zhivotnyh pri modelirovanii holodovoj travmy. [The study of the morphological features in the tissues of experimental animals in the simulation of cold injury]. Vestnik morfologii, 2010; 16(3): 526-528. – (in russian).
- Ivanov V.A., Vitkovskii Iu.A., Mikhailichenko M.I. i dr. Soderzhanie citokinov v krovi bol'nyh pri mestnoj holodovoj travmy. [The content of cytokines in the blood of patients at the local cold injury.] Meditsinskaia immunologiia, 2008; 1: 89-92.
- Lazarev E.V. Ispol'zovanie serotonina adipinata dlia povysheniia effektivnosti konservativnoi terapii kriticheskoi ishemii nizhnikh konechnostei ateroskleroticheskogo geneza. dis. kand. med.nauk [The use of serotonin adipinate to improve conservative therapy of critical ischemia of the limbs of atherosclerotic genesis. cand. med. sci. diss.] Kursk, 2004. 30 p.
- Liashev Iu.D. Opioidnye peptidy kak reguliatory reparativnogo osteogeneza. Dis. dokt. med. nauk [Opioid peptides as regulators of reparative osteogenesis: dr. med. sci. diss.]. Kursk 2002; 55
- Arford, S. Lechenie obmorozheniya: holodnaya-inducirovannogo povrezhdeniya. [Treatment of frostbite: a cold-induced injury.] J. Wound Ostomy Continence Nurs., 2008; 35: 6: 625-630.
- Bilgic S., Ozkan H., Ozenc S. et al. Lechenie obmorozheniya [Treating frostbite.] Can. Fam. Physican., 2008 Mar; 54(3):361-3.
- Wittmers L.E. Jr. Patofiziologiya holodovogo vozdejstviya [Pathophysiology of cold exposure.] Minn. Med., 2001 nov; 84(11): 30-6.
- Yang Z.R., Liu J.Y., Yan P.H. Dejstviya holodovoj akklimacii na gemoreologicheskie povedeniya u krys s obmorozheniem [Effect of cold acclimation on hemorheological behavior in rats with frostbite]. Clin. Hemorheol. Microcirc., 2003; 29(2): 103-9.
Supplementary files
