Fig. 6.

Delayed administration of varespladib following spitting cobra envenoming causes significant reductions in dermonecrosis and myotoxicity in vivo. Groups of mice (n ≥ 4) were injected with either West African (Nigeria) N. nigricollis venom alone or followed by varespladib at a range of different timepoints and via different administration routes. (A) Intradermal coadministration of preincubated venom (110 μg) and varespladib (20 µg) significantly reduced the size of skin lesions caused by West African N. nigricollis venom 72 h later. (B) Intradermal administration of varespladib (100 µg) 0, 15, and 60 min after intradermal venom challenge (110 μg) resulted in significant reductions in the size of venom-induced dermonecrotic lesions. (C) Intravenous delivery of varespladib (100 μg) at 0, 30, 60, and 120 min after intradermal venom challenge (110 μg) resulted in no protection against venom-induced dermonecrosis. (D) Intramuscular delivery of varespladib (10 µg) coincubated with 10 μg venom resulted in significant reductions in plasma CK activity induced by N. nigricollis venom. (E) Intravenous (IV) and intramuscular (IM) delivery of varespladib (100 μg) 0 or 15 min after intramuscular venom challenge (10 μg) resulted in significant reductions in plasma CK activity induced by N. nigricollis venom. For panel A, statistically significant differences were determined by an unpaired t test; for panels B–D, by one-way ANOVAs followed by Dunnett's multiple comparisons post hoc tests. Statistically significant differences are denoted by asterisks: *P < 0.05, ***P < 0.001, and ****P < 0.0001.