Comparative evaluation of human gammaglobulin and methylprednisolone versus Naja atra antivenom in preventing venom-induced ulceration: A cellular and murine model study.

Abstract

Cytotoxins (CTXs) from Naja atra (N. atra) venom induce tissue ulceration, and the efficacy of Chinese N. atra antivenom in preventing venom-induced ulceration is limited. In this study, we purified CTXs from N. atra venom and assessed the preventive effects of human gammaglobulin (HGG) and methylprednisolone (MPS) on ulceration provoked by N. atra venom and CTXs, with Chinese N. atra antivenom as the standard treatment. At the cellular level, within 6 h of exposure, antivenom (5 μl/ml), HGG (100 μg/ml), and low-dose MPS (0.2 μg/ml) significantly improved the survival rate (74 %, 71 %, 73 %) of L6 cells exposed to N. atra venom (2 μg/ml). High-dose MPS (500 μg/ml) showed no protective effect. In mice, antivenom (100 μl/ml), HGG (10 mg/ml), and MPS (400 μg/ml) reduced mortality (0 %, 40 %, and 80 %) and ulcer incidence (0 %, 0 %, 40 %) and area (0 mm, 0 mm, 6.48 mm). Interestingly, delayed HGG administration post-exposure showed superior L6 cell survival rates (82 % vs 55 %) and reduced ulcer incidence (20 % vs 40 %) and area (1.582 mmvs 8.916 mm) compared with antivenom. Notably, the combination of antivenom and MPS resulted in lower survival rates (67 % vs 74 %) in L6 cells and a higher incidence (60 % vs 0 %) of ulcers, with larger ulcer areas (3.359 mmvs 0 mm) compared to those of antivenom alone. In conclusion, HGG demonstrates non-inferior preventive effects against snakebite ulcers compared to antivenom, while MPS, particularly in low doses (0.2 μg/ml), offers limited protection. The combination of antivenom and MPS is not recommended.