Inhibition of Tityus serrulatus venom hyaluronidase affects venom biodistribution

The hyaluronidase enzyme is generally known as a spreading factor in animal venoms. Although its activity has been demonstrated in several organisms, a deeper knowledge about hyaluronidase and the venom spreading process from the bite/sting site until its elimination from the victim's body is s...

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Bibliographic Details
Published in:PLoS neglected tropical diseases 2019-04, Vol.13 (4), p.e0007048-e0007048
Main Authors: Oliveira-Mendes, Bárbara Bruna Ribeiro de, Miranda, Sued Eustáquio Mendes, Sales-Medina, Douglas Ferreira, Magalhães, Bárbara de Freitas, Kalapothakis, Yan, Souza, Renan Pedra de, Cardoso, Valbert Nascimento, de Barros, André Luís Branco, Guerra-Duarte, Clara, Kalapothakis, Evanguedes, Horta, Carolina Campolina Rebello
Format: Article
Language:English
Subjects:
Animals
Antibodies - blood
Antivenins - pharmacology
Body organs
Buthidae
Cancer
Care and treatment
Distribution
Enzymes
Female
Health aspects
Heart
Hemodynamics
Hyaluronidase
Hyaluronoglucosaminidase - antagonists & inhibitors
Inhibition
Injection
Inoculation
Kidney - metabolism
Kidneys
Kinetics
Liver
Lungs
Medical imaging
Mice
Neutralization
Novels
Observations
Organ Specificity
Organs
Peptides
Public health
Radioactivity
Radionuclide Imaging
Reaction kinetics
Scorpion Venoms - pharmacokinetics
Scorpions
Serum
Snakes
Spleen
Spreading
Stings (Injuries)
Technetium
Technetium isotopes
Thyroid
Thyroid gland
Tissue
Tissue Distribution
Tityus serrulatus
Tropical diseases
Venom
Venoms
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Description
Summary:The hyaluronidase enzyme is generally known as a spreading factor in animal venoms. Although its activity has been demonstrated in several organisms, a deeper knowledge about hyaluronidase and the venom spreading process from the bite/sting site until its elimination from the victim's body is still in need. Herein, we further pursued the goal of demonstrating the effects of inhibition of T. serrulatus venom (TsV) hyaluronidase on venom biodistribution. We used technetium-99m radiolabeled Tityus serrulatus venom (99mTc-TsV) to evaluate the venom distribution kinetics in mice. To understand the hyaluronidase's role in the venom's biodistribution, 99mTc-TsV was immunoneutralized with specific anti-T.serrulatus hyaluronidase serum. Venom biodistribution was monitored by scintigraphic images of treated animals and by measuring radioactivity levels in tissues as heart, liver, lungs, spleen, thyroid, and kidneys. In general, results revealed that hyaluronidase inhibition delays venom components distribution, when compared to the non-neutralized 99mTc-TsV control group. Scintigraphic images showed that the majority of the immunoneutralized venom is retained at the injection site, whereas non-treated venom is quickly biodistributed throughout the animal's body. At the first 30 min, concentration peaks are observed in the heart, liver, lungs, spleen, and thyroid, which gradually decreases over time. On the other hand, immunoneutralized 99mTc-TsV takes 240 min to reach high concentrations in the organs. A higher concentration of immunoneutralized 99mTc-TsV was observed in the kidneys in comparison with the non-treated venom. Further, in situ neutralization of 99mTc-TsV by anti-T.serrulatus hyaluronidase serum at zero, ten, and 30 min post venom injection showed that late inhibition of hyaluronidase can still affect venom biodistribution. In this assay, immunoneutralized 99mTc-TsV was accumulated in the bloodstream until 120 or 240 min after TsV injection, depending on anti-hyaluronidase administration time. Altogether, our data show that immunoneutralization of hyaluronidase prevents venom spreading from the injection site. By comparing TsV biodistribution in the absence or presence of anti-hyaluronidase serum, the results obtained in the present work show that hyaluronidase has a key role not only in the venom spreading from the inoculation point to the bloodstream, but also in venom biodistribution from the bloodstream to target organs. Our findings demonstrate tha
ISSN:1935-2735
1935-2727
1935-2735
DOI:10.1371/journal.pntd.0007048