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

J Pharmacol Sci. 2018 Oct;138(2):123-130. doi: 10.1016/j.jphs.2018.08.013. Epub 2018 Sep 27.

Abstract

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.

Keywords: Inflammation; Mice; Oxidative damage; Pressure ulcer; Sodium salt of DNA.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Cyclooxygenase 2 / metabolism
  • DNA / isolation & purification
  • DNA / pharmacology*
  • DNA / therapeutic use*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fishes / metabolism
  • Inflammation Mediators / metabolism
  • Mice, Inbred BALB C
  • Pressure / adverse effects*
  • Receptors, Interleukin-6 / metabolism
  • Reperfusion Injury / complications*
  • Skin / metabolism
  • Skin Ulcer / drug therapy*
  • Skin Ulcer / etiology*
  • Skin Ulcer / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Derinat
  • Inflammation Mediators
  • Receptors, Interleukin-6
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Deoxyguanosine