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.