ВЛИЯНИЕ РИТМИЧЕСКИХ НАГРУЗОК НА УРОВЕНЬ КОГЕРЕНТНОСТИ ЭЛЕКТРИЧЕСКОЙ АКТИВНОСТИ КОРЫ ГОЛОВНОГО МОЗГА

EXPERIMENTAL MODEL OF 5-FLUOURACIL INDUCED ENTERITIS

1Kalinina O.V., 2Polyakova V.S.,  3Pavlovskaya A.I., 4Zgoda V.G.,

1Poryadin G.V., 3Shtil A.A.

1Pirogov Russian Medical University, Moscow, 2Оrenburg State 

Medical University , Orenburg; 3Blokhin Cancer Center, Moscow; 

4Orekhovich Institute of Biomedical Chemistry, Moscow.

A prolonged anticancer chemotherapy with 5-fluorouracil (5FU), the 

drug widely used in many regimens, frequently leads to enteritis, 
thereby interfering with the therapeutic plan and making an intense 
pharmacological correction necessary. To establish an animal model of 
this complication we administered 5FU (500 mg/kg or 100 mg/kg) i.p. 
into С57BL6 and СВА mice as a single injection daily for 5 consecutive 
days. All animals treated with 500 mg/kg 5FU died of acute toxicity by 
days 8-9 after the onset of treatment.  In mice injected with 100 mg/kg 
5FU we observed significantly manifested toxic phenomena including the 
loss of the body weight by 15-20%, a lowered muscle tone, and diarrhea. 
The gross pathological examination at day 6 (5 injections followed by 
one day post treatment) showed that the small and large intestine 
mucosa was clearly thinned. Histological analysis demonstrated mucosal 
atrophy with altered structure of goblet cells and the mucin layer, as 
well as epithelial dysregeneration, shortened villi and crypts, and 
sclerosis. No mitosis was detectable in crypt cells whereas the nuclei
were clear and showed dyskaryosis and euchromatin (with average 1-2 
nucleoli), suggesting that the nuclei were functionally active.
Furthermore, we found cyst-like dilatations in the bowel mucosa. The 
initial histological traits of enteritis can be identified as early as 
at day 2 with 5FU (after 2 injections). The proteomics analysis 
revealed an array of proteins up- or down-regulated in the intestinal 
mucosa of 5FU treated mice. The amounts of individual transcription 
factors, structural and signaling proteins were changed by several 
orders of magnitude compared with the respective levels in intact mice. 
These results indicated that 5FU caused a variety of severe alterations 
in the intestinal mucosa. The molecular events that underlie 5FU 
induced mucosal damage remain to be elucidated. We believe that our 
model is adequate for testing candidate drugs designed to cure this 
clinically unfavorable syndrome.
DOI:10.12737/12361

ВЛИЯНИЕ РИТМИЧЕСКИХ НАГРУЗОК НА УРОВЕНЬ КОГЕРЕНТНОСТИ 

ЭЛЕКТРИЧЕСКОЙ АКТИВНОСТИ КОРЫ ГОЛОВНОГО МОЗГА

Ю.Г. Калинникова, Е.С. Иноземцева, Л.В. Капилевич

Томский государственный университет, Томск, Россия

kisa101090@yandex.ru