title: Acute Lonomia obliqua caterpillar envenomation-induced physiopathological alterations in rats: evidence of new toxic venom activities and the efficacy of serum therapy to counteract systemic tissue damage.
abstract: The clinical manifestations of Lonomia obliqua caterpillar envenomation are systemic hemorrhage and acute kidney injury. In an effort to better understand the physiopathological mechanisms of envenomation, a rat model was established to study systemic tissue damage during L. obliqua envenomation. An array of acute venom effects was characterized, including biochemical, hematological, histopathological, myotoxic and genotoxic alterations. Rapid increases in serum alanine and aspartate transaminases, γ-glutamyl transferase, lactate dehydrogenase, hemoglobin, bilirubin, creatinine, urea and uric acid were observed, indicating that intravascular hemolysis and liver and kidney damage had occurred. Treatment with a specific antivenom (antilonomic serum) for up to 2 h post-venom injection neutralized the biochemical alterations. However, treatment after 6 h post-venom injection failed to normalize all biochemical parameters, despite its efficacy in reversing coagulation dysfunction. The hematological findings were consistent with hemolytic anemia and neutrophilic leukocytosis. The histopathological alterations were mainly related to hemorrhage and inflammation in the subcutaneous tissue, lung, heart and kidneys. Signs of congestion and hemosiderosis were evident in the spleen, and hemoglobin and/or myoglobin casts were also detected in the renal tubules. Increased levels of creatine kinase and creatine kinase-MB were correlated with the myocardial necrosis observed in vivo and confirmed the myotoxicity detected in vitro in isolated extensor digitorum longus muscles. Significant DNA damage was observed in the kidneys, heart, lung, liver and lymphocytes. The majority of the DNA lesions in the kidney were due to oxidative damage. The results presented here will aid in understanding the pathology underlying Lonomia's envenomation.
authors.affiliation: Laboratório de Bioquímica Farmacológica, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500, Cep 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Markus
authors.initials: M
authors.lastname: Berger
authors.forename: Walter Orlando
authors.initials: WO
authors.lastname: Beys-da-Silva
authors.forename: Lucélia
authors.initials: L
authors.lastname: Santi
authors.forename: Iuri Marques
authors.initials: IM
authors.lastname: de Oliveira
authors.forename: Patrícia Mendes
authors.initials: PM
authors.lastname: Jorge
authors.forename: João Antônio Pêgas
authors.initials: JA
authors.lastname: Henriques
authors.forename: David
authors.initials: D
authors.lastname: Driemeier
authors.forename: Maria Aparecida Ribeiro
authors.initials: MA
authors.lastname: Vieira
authors.forename: Jorge Almeida
authors.initials: JA
authors.lastname: Guimarães
mesh_terms: D000818:Animals; D000997:Antivenins / Q000494:pharmacology; D001180:Arthropod Venoms / Q000737:chemistry / Q000633:toxicity*; D001777:Blood Coagulation / Q000187:drug effects; D054715:Cardiotoxins / Q000737:chemistry / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects; D006470:Hemorrhage / Q000188:drug therapy / Q000503:physiopathology; D007299:Insect Bites and Stings / Q000188:drug therapy / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007814:Larva / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009036:Moths / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000997:Antivenins; D001180:Arthropod Venoms; D054715:Cardiotoxins
keywords: Caterpillar; Genotoxicity; Hemorrhagic syndrome; Lonomia; Nephrotoxicity; Venom