[Dinitrosyl-iron complexes with cysteine or glutathione accelerate skin wound healing in animals].
The beneficial effect of NO-donors, dinitrosyl-iron complexes with cysteine or glutathione on the healing of skin wound in rats was demonstrated by hystological and hystochemical methods: dinitrosyl-iron complexes accelerated efficiently repair processes in wound tissue after a twofold injection of an aqueous solution of a dinitrosyl-iron complex into wound tissue at a total dose of 5 mmol on days 1 and 2 after skin wounding, and the granulocyte volume increased 3-4 times on the fourth day after wounding compared with the control. Higher doses of dinitrosyl-iron complex provoked an inflammation process in the wound. Similar experiments with of another NO donor S-nitrosoglutathione affected adversely the wound. S-Nitrosoglutathione was added to the wound at a total dose of 10 mmol, which ensured the administration of NO to the wound tissue in the amount equal to that introduced upon the injection of dinitrosyl-iron complex. The addition of dinitrosyl-iron complex with glutathione at a dose of 2.5 mmol was accompanied by the formation of protein-bound dinitrosyl-iron complex in wound tissue. The formation of dinitrosyl-iron complex was also observed after the injection of S-nitrosoglutathione. However, the amount of complexes was more than 25 times less than that after the administration of dinitrosyl-iron complex. The beneficial effect of dinitrosyl-iron complex on the wound was suggested to be due to the formation of a self-regulated chemical system in wound tissue, which is characterized by the mutual transformation of low-molecular dinitrosyl-iron complex and S-nitrosoglutathione. This system ensures a regulated delivery of NO to its intracellular targets without the formation of high amounts of peroxynitrite which could adversely affect the intracellular processes. It was assumed that the self-regulated system of dinitrosyl-iron complex and S-nitrosoglutathione is not formed after the addition of S-nitrosoglutathione to the wound, probably due to a low amount of intracellular iron which could provide the formation of dinitrosyl-iron complex. The rapid decomposition of S-nitrosoglutathione results in the appearance of high amounts of NO and hence peroxynitrite, which adversely affects the wound.
Shekhter
A B
AB
Rudenko
T G
TG
Serezhenkov
V A
VA
Vanin
A F
AF
D000818:Animals; D003545:Cysteine / Q000032:analysis / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology; D007150:Immunohistochemistry; D007501:Iron / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D026422:S-Nitrosoglutathione / Q000737:chemistry / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000293:injuries*; D014945:Wound Healing / Q000187:drug effects*
D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D026422:S-Nitrosoglutathione; C073661:dinitrosyl iron complex; D007501:Iron; D005978:Glutathione; D003545:Cysteine