Myotoxicity and nephrotoxicity by Micrurus venoms in experimental envenomation

Abstract

Micrurus venoms are essentially neurotoxic but other activities, such as myotoxicity, may be apparent under experimental conditions. Although this myotoxicity has been occasionally reported, there are no studies addressing it systematically across the genus, particularly in its relationship to other systemic manifestations such as renal impairment. The lethal potency of Micrurus fulvius, Micrurus nigrocinctus, Micrurus surinamensis, Micrurus altirostris, Micrurus balyocoriphus and Micrurus pyrrhocryptus venoms determined by us were in the range described for the genus and all venoms exhibited phospholipase activity, albeit at significantly different levels. Intramuscular venom injection caused variable local inflammation-edema; myotoxicity (as determined by plasma creatine kinase levels and histopathology) was apparent only in those venoms with highest phospholipase activity, namely M. fulvius, M. nigrocinctus and M. pyrrhocryptus. Kidneys of animals injected with these strongly myotoxic venoms showed lesions consisting in extensive tubular necrosis with nuclear fragmentation, destruction of the brush border, rupture of basal membrane and epithelial exfoliation of tubular cells, granular cast and thickening of tubules. The histological characteristics of the lesions suggest an important role for indirect glomerular damage by myoglobin deposits. Phospholipase and myotoxic activities did not correlate significantly to the lethal potency; renal lesions were, however, evident only in those venoms that caused extensive muscular damage. Although kidney lesions have not been described in clinical cases of Micrurus envenomation, the potential for nephrotoxicity of some of these venoms should be considered in the overall toxicological picture, at least in experimental conditions.