Estudo dos efeitos fisiopatológicos locais e renais induzidos pela peçonha de Crotalus durissus ssp. do estado da Bahia

Abstract

The ophidian accidents involving species of the genus Crotalus are considered serious and present a high number of deaths. The effects triggered after accidents with this genus can vary intra and interspecifically due to the wide variability of the composition of the venom. Thus, this study evaluated the possible local and renal damages triggered by the venom of Crotalus durissus ssp. of the State of Bahia. For this, male Swiss mice weighing between 20 and 22 g separated in control (inoculated with PBS) and venom (inoculated with 1.5 μg of the Cd-ssp venom) were used. Local damage was assessed by quantification of the local edematogenic reaction, of the cytokines (IL-6 and IL-1β) and by leukocyte migration. Myotoxic damage was assessed by the analysis of creatine kinase (CK) levels. Renal toxicity was assessed, following venom exposure times of 6, 12, 24 and 72 hours, from the analysis of serum creatinine and urea levels, of the sodium excretion fractions (% FENa) and potassium (% FEK), of the levels of malondialdehyde (MDA) and myeloperoxidase (MPO) and of the inflammatory markers (IL-1β, CXCL-1 and IL-18). In addition, the histological analysis of the interplantar region of the plantar cushion, the gastrocnemius musculature and the renal tissue was made. It was observed that the Cd-ssp venom triggered: a) local inflammatory process, assessed by the production of marked edema, Il-1β, Il-6, and the recruitment of leukocytes to the site of inoculation; b) myotoxic process, indicated by increased CK levels at 6, 12 and 24h after inoculation; c) nephrotoxic process confirmed by increased serum creatinine levels (24 and 72 hours), by the increase of % FENa (24 e 72h), of % FEK (72h), by the increase of MPO and of the relative expression of the KIM-1 (12h), Il-1β (12h and 24h) and CxCL-1 (12h); d) increased renal tissue oxidative process by increasing MDA levels. The histological technique demonstrated the presence of inflammatory infiltrate and edema in the interplantar region, necrosis and inflammatory infiltrate in the plantar cushion musculature and gastrocnemius and interstitial vascular ectasia, disorganization of the tubular architecture with marked vacuolization and degeneration of the renal tubular epithelium. It was concluded, therefore, that Cd-ssp venom promoted local alterations, unlike other Brazilian Crotalus, and caused renal alterations confirmed by biochemical, histological and molecular parameters.