Effects of Derinat on ischemia-reperfusion-induced pressure ulcer mouse model.

Sodium salt of deoxyribonucleic acid (DNA), Derinat, isolated from the soft roes of Russian sturgeon, has been utilized as an immunomodulator for the treatment of reactive oxygen species (ROS)-associated diseases in clinics. Here we show that treatment with Derinat has an anti-inflammatory and anti-oxidative effects on cutaneous ischemia-reperfusion (IR) injury in pressure ulcer (PU) model mice. Dorsal skin damage and dermal edema in mild PU model mice were attenuated by treatment with Derinat. Immunohistochemical and biochemical analyses showed that Derinat suppressed IR-induced oxidative damage, i.e. accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), and related inflammatory factors such as cyclooxygenase 2 (COX-2) and IL-6 receptor (IL-6R) in dorsal skin from PU model mice. We also verified that phospholyated/non-phosphorylated ratio of extracellular signal-regulated kinase (Erk) and p38 mitogen-activated protein kinase (MAPK) increased after IR, which were attenuated by Derinat. We then compared the effect of Derinat with that of salmon DNA and other PU therapeutic agents, prostaglandin E1 (PGE1) and basic fibroblast growth factor (bFGF), by using severe PU model mice. The effects of Derinat and salmon-DNA were compatible with those of PGE1 and bFGF. These results suggest that Derinat other fish-derived DNA formulation could be effective enough and become intriguing new therapeutic options.

Natural killer cell cytotoxic activity and c-Fos protein synthesis in rat hypothalamic cells after painful electric stimulation of the hind limbs and EHF irradiation of the skin.

BACKGROUND: The goal was to assess changes in natural killer (NK) cell activity and the number of c-Fos-positive cells in hypothalamic structures induced by painful electrical stimulation and to use extremely high-frequency (EHF) irradiation of the skin to modulate these processes. MATERIAL/METHODS: Experiments were performed on Wistar rats subjected to painful electrical stimulation of the hind limbs combined with EHF irradiation of the skin. The cytotoxic activity of splenic NK cells was assessed by their ability to lyse K-562 tumor cells in vitro. c-Fos-like protein was detected by an immunoperoxidase technique. RESULTS: Painful electric stimulation was associated with a significant decrease in splenic NK cytotoxicity and a dramatic increase in c-Fos-positive cell counts in some hypothalamic structures, particularly in the anterior hypothalamic nucleus (AHN) and the perifornical lateral hypothalamic area (LHA). Two EHF exposures, one before and one after electric stimulation, prevented the suppression of splenic NK cell activity and caused a decrease in the number of c-Fos-positive cells expressed in the ventromedial hypothalamic nucleus (VMH) and basal LHA. Negative correlation was shown between c-Fos-positive cell counts in the AHN and LHA and the cytotoxic activity of NK cells. CONCLUSIONS: These results suggest that painful electric stimulation of the hind limbs of rats causes a reorganization of the central mechanisms that regulate splenic NK cell activity, resulting in a decrease in their cytotoxicity, and that EHF irradiation of the skin prevents this reorganization, thus protecting splenic NK cell activity from the impairment induced by this stressor.

Effect of epitalon on interleukin-1beta signal transduction and the reaction of thymocyte blast transformation under stress.

OBJECTIVES: The aim of this research consisted in studying the effects of tetrapeptide Epitalon on both thymocyte proliferation and interleukin-1beta (IL-1beta) signal transduction via sphingomyelin pathway in the cerebral cortex membranes of mice exposed to stresses exerting diverse effects upon humoral immune response. DESIGN AND SETTING: The experiments were performed on male (CBAxC(57)BL(6))F1 mice aged 8 10 weeks. Two models of experimental stress were used: immune-stimulatory rotation stress and immune-suppressive combined stress (cooling followed by immobilization). The concomitant effect of Epitalon was determined according to its influence on thymocyte proliferation stimulated by concanavalin A at a sub-optimal dose and recombinant IL-1beta. The activity of membrane neutral sphingomyelinase (nSMase), the key enzyme of the sphingomyelin signal transduction pathway, was assayed according to modified Rao and Spence's method (1976). RESULTS: The investigation demonstrated that Epitalon increased thymocyte proliferative activity, both enhanced under rotation stress and suppressed under combined one. It also increased IL-1beta concomitant effect. These findings corresponded to Epitalon effect on diverse stress-induced changes in nSMase activity in cerebral cortex fraction P2. Epitalon activated nSMase in the cerebral cortex membranes of intact mice and increased IL-1beta stimulatory effect on the enzyme activity. CONCLUSIONS: The obtained results provided a conclusive evidence of Epitalon stress-protective effect at the level of IL-1beta signal transduction via sphingomyelin pathway in the nerve tissue, as well as at the level of target thymocyte proliferation.