Experimental Evaluation of Mouse Hind Paw Edema Induced by Iranian Naja oxiana Venom

Document Type: Original Articles


1 Department of Pathology, Bushehr University of Medical Sciences, Bushehr, Iran

2 Department of Aquatic Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

3 Department of Physiology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran

4 School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran

5 Biochemistry Group, The Persian Gulf Tropical Research Center, Bushehr University of Medical Sciences, Bushehr, Iran

6 College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea

7 Department of Human Vaccine and Serum, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran

8 Department of Pharmacology and Toxicology, Bushehr University of Medical Sciences, Bushehr, Iran


Iranian Naja oxiana (Elapidea family) known as cobra snake inhabits in northwestern part of Iran. This study was set out to evaluate the edematogenic potency of the crude venom with intraplantar injection in mice. Additionally, the inhibitory effects of three different drugs (promethazine, dexamethasone, and piroxicam) on paw edema were examined. Moreover , gelatinase activity of this venom with zymography method was assessed.
Paw edema was induced by intraplantar injection of different concentrations of the venom (0.5-5μg dissolved in 50μl of normal saline) in mice (six each). It was estimated by measuring the increase of the paw thickness (%) with a digital caliper. Drugs were pretreated and the rate of changes was measured after the venom injection. Meanwhile, the pathological findings in the treated paws were evaluated with Hematoxylin & Eosin (H&E) staining. Paw thickness reached its maximum amount within 5 minutes and resolved after an hour. This venom had no gelatinase activity with zymography method ruling out its role in edema. It caused nonhemorrhagic diffuse edema with infiltration of inflammatory cells (leukocytes and lymphocytes) in dermis. Pretreatment with drugs intraperitoneally inhibited the venom-induced (1μg/paw) edema significantly, while unexpectedly all mice died a day after piroxicam injection. This in vitro and in vivo preliminary study was shown for the first time that Naja oxiana (N.oxiana) venom induced nonhemorrhagic edema in a short time. Dexamethasone (phospholipase A2 inhibitor, 1mg/kg) and promethazine (H1 inhibitor, 5mg/kg) decreased the venom induced edema (P<0.001). More studies need to be carried out to define the different mediators in venom induced edema formation.