Intraperitoneal administration of butyrate prevents the severity of acetic acid colitis in rats

Abstract

Intrarectal infusion of butyrate improves colorectal disorders including ulcerative colitis (UC). However, it is not established whether systemically administered butyrate benefits such patients. The current study aimed at exploring and comparing the potential of intraperitoneally, intrarectally, and orally administered butyrate against acetic acid (AA)-induced UC in rats. Intrarectal administration of 2 ml of 50% AA was done after or without prior treatment of rats for 7 consecutive days with 100 mg/kg sodium butyrate (SB) intraperitoneally, intrarectally, or orally. Rats were sacrificed after 48 h of AA-treatment. Subsequently, colon sections were processed routinely for histopathological examination. We clinically observed diarrhea, loose stools, and hemoccult-positive stools, and histologically, epithelial loss and ulceration, crypt damage, goblet cell depletion, hemorrhage, and mucosal infiltration of inflammatory cells. The changes were significantly reduced by intraperitoneal, intrarectal, or oral butyrate, with intraperitoneal butyrate exhibiting the highest potency. It is concluded that intraperitoneal administration of butyrate abrogates the lesions of AA-induced UC and its potency surpasses that of intrarectal or oral butyrate.

Keywords: Acetic acid; Butyrate; Intraperitoneal administration; Intrarectal administration; Oral administration; Ulcerative colitis.

Fig. 1

Effect of sodium butyrate on clinical indices of colitis Rats were treated intrarectally with 4% acetic acid alone (A) or after 7 consecutive days of treatment with 100 mg/kg sodium butyrate orally (ABO), intrarectally (ABR), or intraperitoneally (ABP). Values for control rats receiving butyrate alone (B) or physiological saline (S) are also indicated. Results are expressed as the percentage of animals. Eight animals were used for each experimental group

Fig. 2

Effect of sodium butyrate administration on acetic acid (AA) colitis disease activity index Rats were treated intrarectally with 4% acetic acid alone (A) or after 7 consecutive days of treatment with 100 mg/kg sodium butyrate orally (ABO), intrarectally (ABR) or intraperitoneally (ABP). Values for control rats receiving butyrate alone (B) or physiological saline (S) are also indicated. Disease activity index is obtained by combining scores of weight loss, stool consistency, and bleeding divided by 3. Results are expressed as mean±SEM (n=8). ^* Significantly different from AA colitis group at P<0.05. ^# Significantly different from another route of butyrate administration at P<0.05

Fig. 3

Histological sections of rat colon Rats were treated intrarectally with 4% acetic acid alone (a), or following 100 mg/kg sodium butyrate orally (b), intraperitoneally (c), or intrarectally (d and e). (a) Massive hemorrhage, loss of epithelial lining, loss of crypt and villi, and massive infiltration of inflammatory cells due to acetic acid; (b) Considerable intact epithelium under which there is moderate hemorrhage between crypts and villi, loss of some goblet cells, and moderate infiltration of inflammatory cells in the submucosa; (c) A more intact epithelium, mild hemorrhage, and mild infiltration of inflammatory cells; (d) A considerable intact epithelium with severe hemorrhage underneath and destroyed villi and some crypts, and severe loss of goblet cells in villi, severe cellular infiltration in the submucosa; (e) Intercryptal hemorrhage and retention of crypt architecture; (f) The photomicrographs also include those of control rats treated with sodium butyrate alone with no significant changes. Each photo represents 8 animals (4 animals per treatment in duplicate experiments). Hematoxylin and eosin, original magnification ×200

Fig. 4

Histological scores of loss of epithelium (a), crypt damage (b), depletion of goblet cells (c), and infiltration of inflammatory cells (d) Rats were treated intrarectally with 4% acetic acid (AA) alone (A) or after 7 consecutive days of treatment with 100 mg/kg sodium butyrate orally (ABO), intrarectally (ABR), or intraperitoneally (ABP). Results are expressed as mean±SEM of at least 8 individual rats. ^* Significantly different from AA exposed rats (P<0.05); ^# Significantly different from another routes of butyrate administration at P<0.05; ^Φ Significantly different between oral and intrarectal butyrate at P<0.05