The Polyphenol 3, 4, 5 - Tri-hydroxy Benzoic Acid Inhibits Indian Daboia russelli Venom and Its Hemorrhagic Complex Induced Local Toxicity

Y.      H. Mahadeswaraswamy; M.      S. Kumar; Yashonandana      J Gowtham; S.      Nagaraju; K.      S. Girish; K.      Kemparaju

Abstract

Despite a long history on treatment and management of snakebite, as of now, no satisfactory cure exists to treat local toxicity, including anti-venom therapy. Several natural compounds from plants and their synthetic analogs have shown to be protective. In this study 3, 4, 5-tri-hydroxy benzoic acid, the gallic acid (GA) was tested against the local toxicity of Daboia russelli (DR) venom and its purified hemorrhagic complex (HC). GA inhibited in vitro proteolytic activity of both DR venom and HC but, it did not inhibit phospholipase activity of DR venom. GA inhibited hemorrhage, edema forming, dermo- and myonecrotic activities of both HC and DR venom in in vivo experiments. GA was particularly effective against hemorrhagic activity but, GA inhibition had a greater effect on HC when compared to DR venom. The inhibition was likely due to GA induced structural changes in HC as revealed by alterations in fluorescence emission and CD spectral properties. However, the inhibition was not due to chelating property of GA as suggested by UV-visible spectral studies. Inhibition of collagen type IV, laminin and fibronectin degradation essentially provided the biochemical basis for GA which inhibited local effects of HC as well as DR venom. Thus, the study appears highly promising to explore GA and its generics against ruthless local effects and perhaps systemic hemorrhage of DR and other snake bites as well. Further, these agents will possibly find an immense value in the regulation of matrix metalloproteases (MMPs) in processes such as wound healing, inflammation and in the treatment of cancer.

Keywords: Daboia russelli, Gallic acid, Local toxicity, SVMPs inhibition, Hemorrhage, Extracellular matrix, Snakebite, Antivenom, 3, 4, 5-tri-hydroxy benzoic acid, Daboia russelli (DR)