Mechanisms of acute kidney injury induced by experimental Lonomia obliqua envenomation.

Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. To characterize L. obliqua venom effects, we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery-based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman's space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increase the expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. In conclusion, the mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia's envenomation.

Immunochemical detection of Lonomia obliqua caterpillar venom in rats.

Severe cases of human envenoming by caterpillars of the saturniid moth Lonomia obliqua in Brazil can result in renal damage, leading to renal failure, and intracerebral hemorrhaging. In this work, we used immunohistochemical staining with rabbit antiserum raised against L. obliqua venom to examine venom distribution in selected tissues of the brain (cerebellum and hippocampus), kidneys, and liver of male Wistar rats injected with a single dose of venom (200 microg/kg, i.v.) and sacrificed 6, 18, 24, and 72 hours later. The immunolabeling of GFAP was also examined to assess the venom effects on perivascular astrocytic end-feet in the microvasculature of the hippocampus and cerebellum. Venom was detected in the kidneys (6 and 18 hours) and in the liver (6 hours) but not in the brain at any of the time intervals examined. In contrast, immunolabeling for GFAP revealed astrogliosis in the cerebellum and enhanced expression of this protein in the glial processes of the cerebellum and hippocampus, with a maximum response from 24 hours onwards. The high immunoreactivity seen in the kidneys agreed with the renal damage and dysfunction reported for some patients. The lack of venom detection in the brain, despite the altered expression of GFAP in astrocytes, suggested either that the venom does not enter this organ or that its entrance is transient and fast. Alternatively, the circulating venom may induce the release of mediators that could serve as second messengers to provoke the late astrocytic reactivity and astrogliosis. It is possible that both of these mechanisms may contribute to the effects observed.