Episopiloturine protected intestinal mucosa from modifications morphological induced by 5‐fluorouracil in mice: The role of cyclooxygenase‐2
Authors: Barbosa Maria Lucianny Lima , de Negreiros da Silva Ana Vitória Lima Pereira , de Carvalho Vale Larice , Pimenta Helder Bindá , Veras Leiz Maria Costa , Medeiros Jand Venes Rolim , Cerqueira Gilberto Santos 
Published: June 2021

It was aimed check the effect of Epiisopiloturine (EPI) on morphometric changes of villus and crypt in 5‐Fluorouracil (5‐FU) induced intestinal mucositis and to evaluate the expression of Cyclooxygenase‐2 (COX‐2) by immunohistochemistry in 5‐FU‐induced intestinal mucositis.

The experimental protocol was approved by the Ethics Committee on Animal Use (9071050418). The in which the mice received on the first day of the experiment a single dose of 5‐FU (450 mg/kg) via intraperitoneal (i.p), with initiation of EPI treatment from day 2 to day 5. Initially the animals were divided into 5 groups. Group I: received the vehicle solution of 2% at dimethyl sulfoxide (DMSO) in parallel to the other groups treated throughout the study; Group II: received on the first day of the experimental protocol a single dose of 5‐FU i.p. and were treated with a DMSO carrier solution; Group III: received on the first day of the experimental protocol a single dose of 5‐FU i.p and were treated with Epiisopiloturin (10 mg/kg) diluted in 2% DMSO on the next four days. Group IV (Celecoxib): received a single dose of 5‐FU (i.p). On the following days of the experimental protocol only Celecoxib (CLX) (7.5 mg/kg, i.p) was administered. Group V: the animals received a single 5‐FU dose and on the second day of the protocol received EPI (10 mg/kg) diluted in 2% DMSO and Celecoxib (7.5 mg/kg, ip).

After euthanasia, the animals were dissected and the jejunum was collected for the preparation of the slides. After histological processing It was the morphometric evaluation with the help of ImageJ software, where the height of the villi and the depth of the crypts were measured. Immunohistochemistry for COX‐2 was then performed using the streptavidin‐biotin‐peroxidase method.

EPI was able to prevent in a statistically significant way (p <0.05) shortening the villi and decreasing the depth of the crypts caused by 5‐FU. In addition, both the CLX group and the CLX + EPI group prevented villus shortening, with a statistically significant difference when compared to the 5‐FU group.

Regarding the immunohistochemical evaluation, it was observed that the groups treated with EPI 10 mg/kg, CLX and the CLX + EPI combination showed a statistically significant reduction of the immunolabelled area for COX‐2 when compared to the group 5‐FU. It was also found that the combined treatment of CLX + EPI presented a smaller immunolabelled area when compared to the group treated with PPE alone, with a statistically significant difference between groups.

EPI protected the mucosa and decreased COX‐2 expression, demonstrating anti‐inflammatory potential in the 5‐FU induced intestinal mucositis model.

Support or Funding Information

This study received funding of CNPQ and CAPES

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.