Antiinflammatory effects of various drugs on acetic acid induced colitis in the rat

Abstract

The efficacy of various drugs used to treat ulcerative colitis, (sulfasalazine, 5-aminosalicylate, hydrocortisone) was investigated in a model of acetic acid-induced colitis in the rat. Subsequently, we tested the ability of antioxidant/5-lipoxygenase inhibitors (gossypol and nordihydroguiaretic acid [NDGA]) and a cyclooxygenase inhibitor (indomethacin) to attenuate the macroscopic colonic damage and/or neutrophil influx (myeloperoxidase activity [MPO]) associated with this model of colitis. Oral pretreatment with either sulfasalazine, gossypol, or NDGA significantly decreased colonic MPO activity induced by acetic acid. Intrarectal administration of such drugs resulted in an even larger reduction of the colonic inflammation, with gossypol being the most potent compound. Oral or intrarectal administration of corticosteroids (dexamethasone, hydrocortisone) also attenuated the parameters of acetic acid induced colitis. In contrast, pretreatment with indomethacin was ineffective, or when administered daily after colitis induction, indomethacin actually increased colonic neutrophil influx significantly. Our data suggest that both the route of drug administration and dosing regimen employed affect the antiinflammatory potency and/or efficacy of compounds on colitis induced by acetic acid in the rat. Drugs which were effective against this colitis may act by scavenging of oxygen derived free radicals.

Aggravation of Inflammatory Bowel Disease by Cyclooxygenase-2 Inhibitors in Rats

“…The common mechanism of anti-inflammatory action to this class of drugs is the inhibition of COX (COX-1/COX-2), and consequently, the prevention of conversion of arachidonic acid into PGs [9]. However, NSAIDs have been found to be ineffective in reducing the inflammation in IBD perhaps due to a non-specific inhibition of COX enzyme [10,11]. The discovery of the two isoforms of COX, COX-1 that is constitutively expressed in the gastrointestinal tract, and COX-2 which is induced at the site of inflammation, has led to the proposal that selective COX-2 inhibitors will spare gastrointestinal PG synthesis, and therefore also spare gastrointestinal tract damage [12][13][14][15][16][17].…”

I n Vivo Evaluation of 5-ASA Colon-Specific Tablets Using Experimental-Induced Colitis Rat Animal Model

“…Colitis was induced in the distal colon of the rats using 2,4,6-trinitrobenzenesulfonic acid and acetic acid (23)(24)(25)(26). Overall, acetic acid (0.163±0.013) was found to be a stronger colitisinducing agent than 2,4,6-trinitrobenzenesulfonic acid (0.141± 0.0063) as seen in Table IV (Table IV).…”

“…Since in vitro data showed a site-specific drug release, we further evaluated specificity of colon-targeted formulations using two colitis-induced inflammatory in vivo rat models with quantitative estimation of myeloperoxidase activity as the measure of inflammation to provide proof of concept and further confirm that these developed formulations were comparable to colon-specific prodrug sulfasalazine in treating inflammatory bowel conditions. The distal colon colitis was induced using two chemical agents, namely 2,4,6-trinitrobenzenesulfonic acid and acetic acid (23)(24)(25)(26). The objective behind using two colitis-inducing agents was to make their comparative evaluation and to determine whether the formulations developed are effective in acute as well as chronic conditions (21,29).…”

“…Colonic inflammatory lesions were induced (23)(24)(25)(26) in rats by instilling 2,4,6,-trinitrobenzenesulfonic acid (2,4,6-TNBS; Sigma-Aldrich, India) (5% solution in ethanol) at the dose of 20 mg/rat or acetic acid (Qualigens, India; 5% solution in saline) (at the dose of 0.5 ml/rat) instilled into the colon via the anus using the rectal needle under mild anesthesia (ketamine (Neon Laboratories, India) (23 mg/kg injected intraperitoneally). Before inducing colitis, the animals were fasted for 12 h. The animals were allowed water ad libitum during the fasting period.…”

Secretory Event in Intestinal Grafts during Preservation Ischemia

“…These products disrupt cell membranes and are precursors to leukotrienes, prostaglandins, and platelet-activating factor. Inhibitors of other intermediary products in the arachidonic acid cascade such as indomethacin (a cyclooxygenase inhibitor) and nordihydroguiaretic acid (a lipooxygenase inhibitor) are the focus of new drug development to control inflammation and may have beneficial effects in protecting tissues from ischemic injury [6,7]. Likewise, priming of neutrophils in vitro with exogenous sPLA 2 has been shown to cause systemic reperfusion injury in models of rat mesenteric ischemia [8].…”