Banca de DEFESA: ARTHUR HIPÓLITO PEREIRA LEITE

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : ARTHUR HIPÓLITO PEREIRA LEITE
DATE: 31/05/2022
TIME: 14:00
LOCAL: google meet
TITLE:

PRECLINICAL EVALUATION OF THE TOXICITY OF A FIBRINOLYTIC ENZYME PRODUCED BY Mucor subtilissimus

 UCP 1262 IN RATS (Rattus novergicus)

KEY WORDS:

Thrombosis. Fibrinolytic enzymes. Thrombolysis.

PAGES: 113
BIG AREA: Outra
AREA: Multidisciplinar
SUBÁREA: Biotecnologia
SUMMARY:

Thrombosis is characterized as excessive intravascular coagulation, caused by pathological activation of factors of the blood coagulation cascade, with consequent accumulation of the fibrin molecule, the main protein component of thrombus. The pharmacological agents currently used for the treatment of this disorder have high
costs, low specificity for fibrin, and considerable side effects. Thus, new therapeutic strategies are necessary for the effective treatment of thrombosis. Thus, the objective of this work was to evaluate the subacute toxicity of a purified fibrinolytic enzyme produced by the fungus Mucor subtilissimus UCP 1262. For this, the OECD guidelines
for testing chemicals, number 407, entitled "Repeated Dose 28-Day Oral Toxicity Study in Rodents" were followed. We used 50 rats (Rattus novergicus), Wistar variety, randomized into 5 groups (4 test groups and 1 control group), each composed of 10 animals (5 males and 5 females). For 28 days, the test groups were treated with the purified fibrinolytic enzyme, orally (gavage), once a day, diluted in distilled water. The
doses were administered in the following concentrations: group 1 (10 mg/Kg), group 2 (20 mg/Kg), group 3 (40 mg/Kg) and group 4 (satellite) (40 mg/Kg). The control group received only distilled water daily. Each animal had its weight measured on the 1st and 29th day of follow-up, as well as evaluation of possible behavioral changes. On the 29th day, the animals were anesthetized and euthanized for subsequent collection of
blood material, used for hematological, biochemical, and coagulation analyses. The liver was also collected from the animals for further histomorphometric evaluation. During treatment with the purified fibrinolytic enzyme, no change in the behavioral pattern of the animals was observed. Also, no variations in food and water intake were
identified, although significant weight changes were observed in the male animals treated with 20 mg/Kg, 40 mg/Kg and in the satellite group, as well as in the females of the control group, treated with 10 mg/Kg of fibrinolytic enzyme and in the satellite group. Regarding laboratory analyses, a slight reduction in fibrinogen was observed in the females treated with 10 mg/Kg. Regarding the biochemical dosages, a significant reduction in free T3 values was identified. During the necropsy no changes in color, morphology and relative and total weight of the analyzed livers were evidenced. As for the histomorphometric analyses, a reduction in the total number of hepatocytes was observed in the male rats treated with 20 mg/Kg and in the rats treated with 20 mg/Kg
and 40 mg/Kg. Another point observed was an increase in the count of endothelial cells in all rats treated with the fibrinolytic enzyme. The results obtained in the present study demonstrate the need for further preclinical toxicity studies to obtain more safety in the use of the fibrinolytic enzyme analyzed.

BANKING MEMBERS:
Externo à Instituição - THIAGO PAJEÚ NASCIMENTO - UFPI
Presidente - 384972 - ANA LUCIA FIGUEIREDO PORTO
Externo à Instituição - LUCAS ANDRE CAVALCANTI BRANDAO - UFPE
Externa à Instituição - MARLLYN MARQUES DA SILVA - UFRPE
Interna - 2066204 - RAQUEL PEDROSA BEZERRA