Electrophysiological and Structural Aspects in the Frontal Cortex After the Bee (Apis mellifera) Venom Experimental Treatment

Abstract

The aim of this study is to evaluate the bioelectrical and structural-functional changes in frontal cortex after the bee venom (BV) experimental treatments simulating both an acute envenomation and a subchronic BV therapy. Wistar rats were subcutaneously injected once with three different BV doses: 700 μg/kg (T(1) group), 2100 μg/kg (T(3) group), and 62 mg/kg (sublethal dose-in T(SL) group), and repeated for 30 days with the lowest dose (700 μg/kg-in T(S) group). BV effects were assessed by electrophysiological, histological, histochemical, and ultrastructural methods. Single BV doses produced discharges of negative and biphasic sharp waves, and epileptiform spike-wave complexes. The increasing frequency of these elements suggested a dose-dependent neuronal hyperexcitation or irritation. As compared to the lower doses, the sublethal dose was responsible for a pronounced toxic effect, confirmed by ultrastructural data in both neurons and glial cells that underwent extensive, irreversible changes, triggering the cellular death. Subchronic BV treatment in T(S) group resulted in a slower frequency and increased amplitude of cortical activity suggesting neuronal loss. However, neurons were still stimulated by the last BV dose. Structural-functional data showed a reduced cellular density in frontal cortex of animals in this group, while the remaining neurons displayed both specific (stimulation of neuronal activity) and unspecific modifications (moderate alterations to necrotic phenomena). Molecular mechanisms involved in BV interactions with the nervous tissue are also discussed. We consider all these data very important for clinicians who manage patients with multiple bee stings, or who intend to set an appropriate BV therapy.