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.
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