B~11etin of Experimental Biology and Medicine, Vol. 126, No_ I0, October, 1998 1017 PHARMACOLOGY AND TOXICOLOGY Dermaprotecting Properties of Sodium Succinate under Conditions of Impaired Circulation P. A. Galenko-Yaroshevskii, I. S. Chekman, O. S. Medvedev, V. I. Kondratyuk, K. S. Vas'kov, A. V. Uvarov, S. E. Gumenyuk, V. N. Kovalenko, P. B. Popov, and V. L. Popkov Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 10, pp. 420-424, October, 1998 Original article submitted January 13, 1997 Sodium succinate improves the survival of a skin graft in mice, rats, and dogs, normalizes histamine and serotonin concentrations in the epidennis and blood, exhibits antitoxic aclivity, improves microcirculation in the skin, brain, heart, kidneys, and testes without any ap- preciable effect on systemic arterial pressure, cardiac function, and liver blood flow in rats. Key Words: sodium succinate; dermaprotecting activity; microcirculation Microcirculation disorders accompanying skin plasty and leading to partial or complete necrosis of the recipient's skin or skin graft [1] can be corrected by drugs that increase the viability of ischemized skin and by preventing and correcting microcircula- tory disorders. Sodium succinate (SS) has been used as an endogenous adaptogen that increases tissue resis- tance to damaging factors [2,6]. It was suggested that it can be employed as an agent preventing inflammation and stimulating the growth of the epithelium [3,5]. By improving oxidation and energy metabolism in various tissues, SS may play an sub- stantial role in detoxifying therapy [2,4,7,8]. In the present study we assessed the dermapro- tective activity of SS and examined SS effects on systemic and regional hemodynamics. MATERIALS AND METHODS Experiments were performed on 159 mice, 237 rats, and 48 dogs. The acute toxicity doses (LDs0) were Department of Pharmacology, Kuban' State Medical Academy, Krasnodar; Department of Pharmacology, Ukrainian National Medical University, Kiev; Laboratory of Pharmacology, Cardiology R~search- and-Production Center, Ministry of Health, Moscow determined in mice. The antinecrotic activities of SS and of the reference preparations lithium suc- cinate and lithimn oxybutyrate (this compound pos- sesses high dermaprotective activity [11[) were as- sessed in mice, rats, and dogs as described [9]. The antinecrotic activity was regarded as the ability of the studied compounds to improve the sin-rival of a pedicle skin graft. The mean effecti~,e dose (EDs(,) and antinecrotic hldex LDJEFs0), which characterize the spectrum of the studied pharmacological effect. The effect of SS on the contents of the in- flammation mediators histamine and serotonin in the epidermis and blood was examined in male albino rats. Twenty-four hours before the experi- ment, skin on the back was depilated with 10% sodium sulthte. Pedicle skin graft was taken fiom rats under sodium pentobarbital anesthesia (40 rag/ kg intraperitoneally). Experilnental animals were injected with SS (5% solution, 100 mg/kg) on the day of the surgery and for two days after it. Control rats were injected with an equal volume of normal saline. The rats were decapitated after 3 days. Paral- lel measurements were performed in experimental, control, and intact rats. The histamine 1121 and serotonin [13] contents in the graft epidermis were measured spectrofluofimetrically at least in 3 rats. 0007-4888/98/0010-01017520.00 9 Kluwer Ac'ademic/Plenum PtJblishers