Russell’s viper venom induced nephrotoxicity, myotoxicity, and hepatotoxicity—Neutralization with gold nanoparticle conjugated 2-hydroxy-4-methoxy benzoic acid in vivo.

Snakebite is one of the major neglected tropical diseases and health hazard that leads to significant mortality, particularly in rural populations of tropical and subtropical countries including India. Antisnake venom serum (ASVS) is the only specific treatment against snake envenomation. Available treatment i.e. ASVS have many limitations not only low efficiency but also considerable side effects. Search for alternative ASVS is a major domain in toxinology research. Targeted drug therapy using nanoparticles, an emerging area of nanotechnology, is one such alternative. Here, we studied neutralization of ing Russell’s viper venom (RVV) induced toxicity (nephrotoxicity, myotoxicity, hepatotoxicity) with gold nanoparticle-conjugated 2-hydroxy-4-methoxy benzoic acid (GNP-HMBA) in male albino mice. We conjugated 2-hydroxy-4-methoxy benzoic acid (HMBA) with gold nanoparticle (GNP) by adsorption method, and physico-chemical characterization were done by DLS, ZETA potential, FTIR and TEM. Swiss male albino mice were divided into four groups viz., sham control, venom control, HMBA treated and GNP-HMBA treated. Each group had four mice (n=4). RVV was injected in all groups except sham control. Groups 3 and 4 had treatment with HMBA and GNP-HMBA, respectively. After 24 h, blood and urine were collected. Serum LDH, CK, SGPT, SGOT, γ-GT, ACP, ALP, urea, creatinine and urinary calcium and urinary phosphorus were measured. The hydrodynamic diameter of GNP-HMBA was 65-75 nm and TEM diameter was 18-28 nm. The serum/urine parameters were found significantly increased in venom control group. Degree of RVV neutralization was GNP-HMBA > HMBA. Treatment with GNP-HMBA showed partial protection of histopathological changes in RVV-induced kidney and liver tissues. It may be concluded that GNP-HMBA neutralized RVV-induced toxicities (nephrotoxicity, myotoxicity and hepatotoxicity) in male albino mice. Further studies are warranted in the development of alternative herbal-nanoparticle antidote against snake venom induced toxicity.

Purification, Biochemical Properties, and Activities of a Novel Factor X Activator (F V e-1 ) from Daboia Russelli Siamensis ( Myanmar ) Venom / 中山大学学报(医学科学版)

[Objective] To purify and characterize a novel factor X activator,Fve-1 from Daboia russelli siamensis (Myanmar) venom.[ Methods]F V e-1 was purified by ion-exchange chromatography and gel filtration.The hemostatic activity of F V e-1 was determined based on chromogenic substrates.The fibrinogen-clotting activity of F V e-1 was also determined.Thermal stability, pH stability,enzyme activity,and inhibition of F V e- 1 were determined by its remaining procoagulant activity.N-treminal sequence was determined by the method of automated Edman degradation.[ Results ]F V e-1 was achieved by chromatography with a molecular weight of 13,808 and an isoelectric point of 4.6. The hemostatic activity of 0.5 mg Fve-1 was equal to that of 1.5625 u thrombin or that of 54.93 ng RVV X. F V e-1 primarily activated F X, but did not affect on prothrombin and fibrinogen. The suitable pH and temperature range of F V e-1 was 6.5-7.5 and 25-60 ℃,respectively.The activity of F V e-1 was enhanced by Ca2+ and inhibited by EDTA and DTT.The N-terminal sequence of F V e-1 was NH2-N-L-Y-Q-F-G-E-M-I-N.[Conclusion] F V e-1 is a factor X-activating enzyme,which could activate FX to FX a,but have minimal effect on prothrombin and fibrinogen.

Inhibition of local effects of Indian Daboia/Vipera russelli venom by the methanolic extract of grape (Vitis vinifera L.) seeds.

Although anti-venom therapy is available for the treatment of fatal bite by snakes, it offers less or no protection against the local effects such as dermo- and myonecrosis, edema, hemorrhage and inflammation at the bitten region. The viper species are known for their violent local effects and such effects have been commonly treated with plant extracts without any scientific validation in rural India. In this investigation, the methanolic extract of grapes (Vitis vinifera L.) seed was studied against the Indian Daboia/Vipera russelli venom-induced local effects. The extract abolished the proteolytic and hyaluronidase activities and also efficiently neutralized the hemorrhage, edema-inducing and myonecrotic properties of the venom. In addition, the extract also inhibited partially the pro-coagulant activity of the venom and abolished the degradation of Aα and Bβ chains of human fibrinogen. Thus, the extract possesses potent anti-snake venom property, especially against the local effects of viper bites.