RESUMO
Hyaluronidases (HYALs) are enzymes ubiquitously found in venoms from diverse animals and seem to be related to venom spreading. HYAL activity might be important to Tityus spp. envenoming, since anti-Tityus serrulatus HYAL (TsHYAL) rabbit antibodies neutralize T. serrulatus venom (TsV) lethality. The present work aimed to verify and compare HYAL activity of venoms from other Brazilian Tityus spp. (Tityus bahiensis, Tityus stigmurus and Tityus obscurus) and to test whether anti-TsHYAL antibodies and Brazilian horse therapeutic scorpion antivenom (produced by Fundação Ezequiel Dias (FUNED), Butantan and Vital Brazil Institutes) can recognize and inhibit HYAL activity from these venoms. In ELISA assays, anti-TsHYAL and scorpion antivenoms recognized T. serrulatus, T. bahiensis and T. stigmurus venoms, however, they demonstrated weaker reaction with T. obscurus, which was also observed in Western blotting assay. Epitope mapping by SPOT assay revealed different binding patterns for each antivenom. The assay showed a weaker binding of scorpion antivenom produced by FUNED to peptides recognized by anti-TsHYAL antibodies. Anti-TsHYAL antibodies and antivenoms produced by Butantan and Vital Brazil institutes inhibited HYAL activity of all tested venoms in vitro, whereas FUNED antivenom did not show the same property. These results call attention to the importance of hyaluronidase inhibition, that can aid the improvement of antivenom production.
Assuntos
Antivenenos/química , Hialuronoglucosaminidase/farmacologia , Venenos de Escorpião/química , Sequência de Aminoácidos , Animais , Sítios de Ligação de Anticorpos , Brasil , Ensaio de Imunoadsorção Enzimática , Mapeamento de Epitopos , Hialuronoglucosaminidase/antagonistas & inibidores , Imunoensaio , Modelos Moleculares , Coelhos , Análise de Sequência de ProteínaRESUMO
Animal venoms are a mixture of bioactive compounds produced as weapons and used primarily to immobilize and kill preys. As a result of the high potency and specificity for various physiological targets, many toxins from animal venoms have emerged as possible drugs for the medication of diverse disorders, including cardiovascular diseases. Captopril, which inhibits the angiotensin-converting enzyme (ACE), was the first successful venom-based drug and a notable example of rational drug design. Since captopril was developed, many studies have discovered novel bradykinin-potentiating peptides (BPPs) with actions on the cardiovascular system. Natriuretic peptides (NPs) have also been found in animal venoms and used as template to design new drugs with applications in cardiovascular diseases. Among the anti-arrhythmic peptides, GsMTx-4 was discovered to be a toxin that selectively inhibits the stretch-activated cation channels (SACs), which are involved in atrial fibrillation. The present review describes the main components isolated from animal venoms that act on the cardiovascular system and presents a brief summary of venomous animals and their venom apparatuses.
