Banca de QUALIFICAÇÃO: ADAILSON DE SOUZA ASSUNÇÃO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : ADAILSON DE SOUZA ASSUNÇÃO
DATE: 14/02/2025
TIME: 09:00
LOCAL: Virtual Google Meet: https://meet.google.com/dew-gihe-kkj
TITLE:

Synthetic N-methyl analogue of the alkaloid caulerpine attenuates the inflammatory process
in murine models of peritonitis, ear edema and acute lung injury.

 

KEY WORDS:

Inflammation. Exudate. Cytokine. Leukocytes.

PAGES: 62
BIG AREA: Ciências Biológicas
AREA: Imunologia
SUMMARY:

Caulerpine (CLP) is an alkaloid extracted from the seaweed Caulerpa racemosa with anti-inflammatory properties
previously demonstrated in our laboratory. Through structural modifications in the indole nucleus and in the ester
group of classic caulerpine, an analogue, called N-methyl, was generated, which facilitates its lipophilicity. Thus, the
present study aimed to evaluate the action of the N-methyl analogue of caulerpine (CLP Nmt) in a murine model of
peritonitis caused by zymosan, ear edema induced by xylol and acute lung injury caused by lipopolysaccharide (LPS),
comparing it with CLPc and dexamethasone. In the peritonitis model, male Swiss mice were treated orally with
classical CLP (CLPc, 2 mg/kg), CLP Nmt (4, 2 and 1 mg/kg) and intraperitoneally with dexamethasone (Dexa, 1 mg/kg)
and one hour later received zymosan (40 mg/kg) intraperitoneally. After 24 hours, the mice were euthanized and
peritoneal lavage was performed, which was centrifuged, and the leukocyte count was determined in the Neubauer
chamber and the supernatant was used to measure IL-6, IFN-, TNF-α and IL-1β, by ELISA. For the ear edema model,
the Swiss mice were treated with the N-methyl analogue at the dose that best inhibited peritonitis (2 mg/kg), and the
other treatments mentioned above, applied by topical application of xylene (40 μL) in the right ears. One hour after
treatment, the left and right ears were removed and weighed on a precision scale to calculate the percentage of
edema inhibition and then placed in PBS/10% formalin for histological analysis. In the acute lung injury model, the
animals were treated orally with CLPc (2 mg/kg), CLP Nmt (2 mg/kg) and intraperitoneally with dexamethasone (1
mg/kg). One hour later, the animals received 50 μl of LPS (100 μg/kg) intranasally. After 24 hours, the mice were
euthanized, the bronchoalveolar lavage (BAL) was collected, centrifuged, the cell button was used for total and
differential leukocyte counts, and the supernatant was used to measure the levels of cytokines mentioned above and
nitric oxide (NO) dosage by Griess. In addition, radiation samples were processed for histological analysis and also for
RNA removal to evaluate the expression of inflamed patches. The results obtained showed that treatment with the N-
methyl analog is effective in decreasing cell circulation and IL-6 circumference in the peritoneal cavity, with a dose of
2 mg/kg being the most effective in this inhibition. Because of this result, this was the dose used as a standard for the
other experiments. Thus, it was obtained that the analog showed the ability to significantly inhibit edema formation
in the ear edema model, similarly observed for CLPc and dexa, in addition to inhibiting leukocyte recruitment to the
lung cavity, predominantly polymorphonuclear, and decreasing the levels of IL-6, IFN-γ, TNF-α and NO in BAL, in
addition to helping to reduce lung damage. These results demonstrated the potential of the N-methyl analogue in
reducing the inflammatory process in rich murine models, similar to what was tested for CLPc and compared with the
data obtained for dexamethasone, making this analogue a potential pharmacological target.

 

COMMITTEE MEMBERS:
Presidente - 1346635 - JANEUSA TRINDADE DE SOUTO
Interna - 1049952 - DEYSIANE OLIVEIRA BRANDAO
Externa ao Programa - ***.788.694-** - JULIANE SANTOS DE FRANÇA DA SILVA - UFPB