Acute toxicity of the recombinant and native phα1toxin: New analgesic from phoneutria nigriventer spider venom

Abstract

Phα1β, a purified peptide from the venom of the spider Phoneutria nigriventer, and its recombinant form CTK 01512-2 are voltage-dependent calcium channel (Ca V ) blockers of types N, R, P/Q, and L with a preference for type N. These peptides show analgesic action in different pain models in rats. The aim of this study was to evaluate the acute intrathecal toxicity of the native and recombinant Phα1β toxin in Wistar rats. Clinical signs, serum biochemistry, organ weight, and histopathological alterations were evaluated in male and/or female rats. Dyspnea was observed in males, hyporesponsiveness in females, and Straub tail and tremors in both genders. There were no significant differences in male organ weight, although significant differences in the female relative weight of the adrenal glands and spleen have been observed; these values are within the normal range. Serum biochemical data revealed a significant reduction within the physiological limits of species related to urea, ALT, AST, and FA. Hepatic and renal congestion were observed for toxin groups. In renal tissue, glomerular infiltrates were observed with increased glomerular space. These histological alterations were presented in focal areas and in mild degree. Therefore, Phα1β and CTK 01512-2 presented a good safety profile with transient toxicity clinical signals in doses higher than used to obtain the analgesic effect.