Development and efficacy evaluation (in vitro and in vivo) of a hemoperfuser cartridge for the antiophidian treatment

• Grant number: 15/01420-9
• Support type: Regular Research Grants
• Duration: August 01, 2016 - January 31, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Clinical Pharmacology
• Principal researcher: Yoko Oshima Franco
• Grantee: Yoko Oshima Franco
• Home Institution: Pró-Reitoria Acadêmica. Universidade de Sorocaba (UNISO). Sorocaba , SP, Brazil
• Assoc. researchers: Valquíria Miwa Hanai Yoshida

Abstract

A serious complication to poisoning caused by venomous snakes (Bothrops and Crotalus) is the Acute Kidney Injury (AKI). The prevention of AKI should be attempted in all patients envenomed by venomous animal by early administration of specific antivenom treatment of hypotension, shock and maintaining an adequate state of hydration. On the other hand, phytochemicals as tanin/tannic acid show ability in precipitating proteins from snake venoms, but its intravenous administration is not recommended since could also precipitate proteins from blood. An interesting alternative would be the hemoperfusion. Objectives. Using the hemoperfusion technology, the objectives of this study are to develop and to evaluate in vitro a hemoperfuser cartridge in order to evaluate the ability in the removal of venom (simulated hemoperfusion) and after to test the efficacy (and complications) using an animal model (Wistar rats). Method. The cartridge will be developed by combining activated carbon granules (different sizes) trapped between layers of permeable polymeric material (eg, polyurethane) conjugated tannic acid/tannin derived from medicinal plants (different proportion). The animals will be divided into 6 groups: group I - Bothrops jararaca venom (vBj) i.p. , after 2 h, PBS e.v.; group II - Crotalus durissus terrificus venom (vCdt) i.p., after 2 h ,PBS e.v.; group III - vBj i.p., after 2 h, specific antivenom e.v.; group IV - vCdt i.p., after 2 h, specific antivenom e.v.; Group V - vBj i.p., after 2 h, hemoperfusion; Group VI - vCdt i.p., 2 h after, hemoperfusion, The injected doses of snake venoms will be the LD50 of vBj and vCdt obtained from the literature, as following: 12.5 mg/kg and 180 µg/100 g, respectively. Immediately after treatments, each group will be placed in appropriate metabolic cages for urine collection (24 h after venom injection). Immediately after urine collection, animals will be anesthetized for blood and kidneys (renal medulla and cortex) collection. Expected Results. If the model is effective can be applied to prevent the AKI decreasing the human death rate and in Veterinary Medicine, production animals (cattle, pigs, goats, etc.) and "pets" (dogs , cats, etc.); reduction of public spending in the production of antivenom and time reduction of hospital stay (human or animal) of the serious injuries induced by venomous animals. Keywords: Bothrops jararaca. Crotalus durissus terrificus. Hemoperfusion. Ophidian accident. Tannic acid. (AU)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NETO MORENO, DEBORA ANTUNES; SALADIN, MIRELA SANTOS; MARQUES VIROEL, FABIA JUDICE; JUSTE DINI, MURILO MELO; PICKIER, THAISA BORIM; AMARAL FILHO, JORGE; DOS SANTOS, CAROLINA ALVES; HANAI-YOSHIDA, VALQUIRIA MIWA; GROTTO, DENISE; GERENUTTI, MARLI; et al. Are Silver Nanoparticles Useful for Treating Second-Degree Burns? An Experimental Study in Rats. ADVANCED PHARMACEUTICAL BULLETIN, v. 11, n. 1, p. 130-136, 2021. (12/08271-0, 15/01420-9, 08/11005-5)

DOS SANTOS, MARCIO G.; MORENO, FELIPE S.; DE OLIVEIRA, AKILA L.; OLIVEIRA, ISADORA C. F.; TRIBUIANI, NATALIA; COGO, JOSE C.; SCRIBONI, ANDREIA B.; COGO-MUELLER, KARINA; SAN FELICIANO, ARTURO; BONOMINI, TIAGO JOSE; et al. New pharmacological insights of Galactia glaucescens. NATURAL PRODUCT RESEARCH, v. 33, n. 16, p. 2389-2393, AUG 18 2019. (14/26786-3, 15/01420-9, 12/08271-0)

FONTANA OLIVEIRA, ISADORA CARUSO; DALLA MORA, ADRIANA; NETO, JAIRO BRAGA; DE OLIVEIRA, AKILA LARA; HARDER, CAROLINA; HANAI-YOSHIDA, VALQUIRIA MIWA; COGO, JOSE CARLOS; FLORIANO, RAFAEL STUANI; BONVENTI JUNIOR, WALDEMAR; OLIVEIRA, SARA DE JESUS; et al. Prospective study of a Bothrops jararacussu venom batch (Bj2015) - phospholipase A(2) activity, immunogenicity, neurotoxicity, and myotoxicity parameters. NATURAL PRODUCT RESEARCH, v. 33, n. 16, p. 2417-2421, AUG 18 2019. (15/01420-9, 12/08271-0)

FONTANA OLIVEIRA, ISADORA CARUSO; DE PAULA, MARINA OLIVEIRA; BOSCHILHA LASTRA, HELLEN CRISTINE; ALVES, BRUNO DE BRITO; NETO MORENO, DEBORA ANTUNES; YOSHIDA, EDSON HIDEAKI; AMARAL FILHO, JORGE; COGO, JOSE CARLOS; VARANDA, ELIANA APARECIDA; RAI, MAHENDRA; et al. Activity of silver nanoparticles on prokaryotic cells and Bothrops jararacussu snake venom. DRUG AND CHEMICAL TOXICOLOGY, v. 42, n. 1, p. 60-64, JAN 2 2019. (15/01420-9, 12/08271-0, 08/11005-5)

HARDER, CAROLINA; DE OLIVEIRA, AKILA LARA; SCRIBONI, ANDREIA BORGES; OLIVEIRA CINTRA, ADELIA CRISTINA; SCHEZARO-RAMOS, RAPHAEL; DOS SANTOS, MARCIO GALDINO; COGO-MUELLER, KARINA; HASHIMOTO MIURA, REGINA YURI; FLORIANO, RAFAEL STUANI; ROSTELATO-FERREIRA, SANDRO; et al. Pharmacological Properties of Vochysia Haenkeana (Vochysiaceae) Extract to Neutralize the Neuromuscular Blockade Induced by Bothropstoxin-I (Lys49 Phospholipase A(2)) Myotoxin. ADVANCED PHARMACEUTICAL BULLETIN, v. 7, n. 3, p. 433-439, SEP 2017. (15/01420-9, 12/08271-0)

OLIVEIRA, ISADORA CARUSO FONTANA; YOSHIDA, EDSON HIDEAKI; DINI, MURILO MELO JUSTE; PASCHOAL, ANA BEATRIZ OLIVIO; COGO, JOSE CARLOS; DA CRUZ-HOFLING, MARIA ALICE; HYSLOP, STEPHEN; OSHIMA-FRANCO, YOKO. Evaluation of Protection by Caffeic Acid, Chlorogenic Acid, Quercetin and Tannic Acid against the In Vitro Neurotoxicity and In Vivo Lethality of Crotalus durissus terrificus (South American Rattlesnake) Venom. TOXINS, v. 13, n. 11, NOV 2021. (15/01420-9)

OLIVEIRA, MAXIMILIAN ESTEVAN; CAMPANHOLI, JESSICA; CAVALCANTE, ROBERTA LIMA; MORENO, FELIPE SILVEIRA; YOSHIDA, EDSON HIDEAKI; DINI, MURILO MELO JUSTE; ARANHA, ELVIO FRANCO DE CAMARGO; COGO, JOSE CARLOS; DIAS, LOURDES; HYSLOP, STEPHEN; et al. Experimental model for removal of snake venom via hemoperfusion in rats. JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, v. 30, n. 3, p. 286-294, MAY 2020. (15/01420-9)