Inhibition of Tityus serrulatus venom hyaluronidase affects venom biodistribution

摘要

Author summary Hyaluronidases are known as the venom components responsible for disseminating toxins from the injection site to the victim's organism. Therefore, understanding how the venom distribution occurs and the role of hyaluronidases in this process is crucial in the field of toxinology. In this study, we inhibited Tityus serrulatus venom (TsV) hyaluronidase's action using specific anti-Ts-hyaluronidase antibodies. Labeling TsV with a radioactive compound enabled monitoring of its biodistribution in mice. Our results show that, upon hyaluronidase inhibition, TsV remains at the injection site for longer, and only a reduced amount of the venom reaches the bloodstream. Consequently, the venom arrives later at target organs like the heart, liver, lungs, spleen, and thyroid. Considering the possible application of hyaluronidase inhibition as a therapeutic resource in envenoming first-aid treatment, we performed the administration of hyaluronidase neutralizing antibodies at different times after TsV injection. We observed that TsV remains in the bloodstream and its arrival at tissues is delayed by 120 or 240 min after TsV injection, depending on anti-hyaluronidase administration times. Our data show that hyaluronidase plays a crucial role in TsV spreading from the injection site to the bloodstream and from the bloodstream to the organs, thus suggesting that its inhibition can help to improve envenoming's treatment.