EFFECT OF D-002 ON ACETIC ACID-INDUCED COLITIS IN RATS AT SINGLE AND REPEATED DOSES

doi:10.1006/phrs.1999.0596

Pharmacological Research

Volume 41, Issue 4, April 2000, Pages 391-395

https://doi.org/10.1006/phrs.1999.0596 Get rights and content

Abstract

D-002 is a natural mixture of higher aliphatic primary alcohols purified from beeswax, with mild anti-inflammatory and effective antiulcer effects experimentally proved. Furthermore, it reduces leukotriene (LTB₄) in the exudate of carrageenan-induced pleurisy and has a protective effect on the pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea pig. This study was conducted to determine the effect of D-002 on acetic acid-induced colitis in rats at single and repeated doses. In a first series, D-002 was orally administered at 25 and 50 mg kg⁻¹, 24 h before the induction of colitis, meanwhile, in a second series, it was administered 24 h after the induction of colitis. Two other series (III and IV) examined the protective and therapeutic effect of D-002 administered for 7 days at the same doses, before or after colitis induction. Significant reductions in wet weight, macroscopic injury, polymorphonuclear infiltration and wall thickness were observed in colonic mucosa of D-002-treated animals compared with controls in both protective and therapeutic alternatives. It is concluded that D-002 was effective to protect or prevent the damage associated to acetic acid-induced colitis.

References (22)

D Carbajal et al.
An ti-inflammatory activity of D-002, an active product isolated from beeswax
Prostagland Leukotrienes Essent Fatty Acids
(1998)
J Wallace et al.
Exacerbation of experimental c olitis by nonsteroidal anti-inflammatory drugs is not related to elevated leukotriene B4 synthesis
Gastroenterology
(1992)
G Nygard et al.
Acute indomethacin-induced jejunal injury in the rat
Gastroenterology
(1994)
D Rachmilewitz et al.
Inflammatory mediators of experimental colitis in rats
Gastroenterology
(1989)
G Morris et al.
Hapten-induced model of chronic inflammation and ulceration in the rat colon
Gastroenterology
(1989)
SS Baker et al.
Rat enterocyte injury oxygen-dependent processes
Gastroenterology
(1991)
D Carbajal et al.
Anti-ulcer activity of higher primary alcohols of beeswax
J Pharm Pharmacol
(1995)
D Carbajal et al.
Possible mechanism cytoprotective of D-002
J Pharm Pharmacol
(1996)
N Mascolo et al.
Acetic acid-induced colitis in normal and essential fatty acid deficient rats
J Pharmacol Exp Ther
(1995)
M Noa et al.
Effect of D-002 on the pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea pig
J Pharm Pharmacol
(1998)

There are more references available in the full text version of this article.

Cited by (23)

Algal Polysaccharides, Novel Application, and Outlook
2017, Algae Based Polymers, Blends, and Composites: Chemistry, Biotechnology and Materials Science
Algal polysaccharides are obtained from algae. Marine algae contain high amount of polysaccharides including mucopolysaccharides, cell wall–structured, and storage polysaccharides. Polysaccharides content in some seaweed species ranges from 4% to 76% of their total dry weight. Highest polysaccharide contents are found in species such as Ulva, Ascophyllum, Palmaria, and Porphyra. Polysaccharides obtained from algae are critically important for industrial and nutritional purposes. Various industrial applications include their use as thickeners, stabilizers, emulsifiers, feed, beverages, food, pharmaceuticals, etc. From nutrition point of view, seaweeds are low in calories and lipid content but high in indigestible carbohydrate content which is good for the intestine. Alginates, ulvans, carrageenans, fucoidans, and chitin have numerous industrial, especially pharmaceutical and biomedical, applications with rapidly increasing usage and commercial value.
Protective effect of sanguinarine against acetic acid-induced ulcerative colitis in mice
2013, Toxicology and Applied Pharmacology
Citation Excerpt :
Acetic acid-induced colitis is an easily inducible model of IBD, and the similarity of the inflammatory mediator profile to IBD suggests that the inflammatory phase bears some resemblance to acute human intestinal inflammation (Elson et al., 1995). Among various animal models of intestinal inflammation, acetic acid-induced colitis is one of the widely used models (MacPherson and Pfeiffer, 1978; Noa et al., 2000; Sasaki et al., 2000), which uses intrarectal administration of dilute solutions of acetic acid to produce a diffuse colitis in mice, and the resulting colonic inflammation is characterized by increased neutrophils infiltration into the intestinal tissue, edema and ulceration. One of the important intestinal tissue damage mechanisms is oxidative stress through an excessive production of reactive oxygen metabolites (ROM), including superoxide anion, hydrogen peroxide, hypochlorous acid and hydroxyl radical (Kruidenier and Verspaget, 2002).
The quaternary ammonium salt, sanguinarine (SANG), is of great practical and research interest because of its pronounced, widespread physiological effects, which promote anti-microbial and anti-inflammatory responses in experimental animals. Although SANG is originally shown to possess anti-inflammatory properties and it has been used to treat various inflammatory diseases, its effects on ulcerative colitis have not been previously explored. The aim of the present study is to evaluate the effect of SANG on acetic acid-induced ulcerative colitis in mice. Experimental animals received SANG (1, 5 and 10 mg/kg, p.o.) and sulfasalazine (500 mg/kg, p.o.) for seven consecutive days after induction of colitis by intra-rectal acetic acid (5% v/v) administration. The colonic mucosal injury was assessed by clinical, macroscopic, biochemical and histopathological examinations. SANG treatment significantly decreased mortality rate, body weight loss, disease activity index (DAI), wet colon weight, macroscopic and histological score when compared to acetic acid-induced controls. In addition, administration of SANG effectively inhibited p65 NF-κB protein expression and MPO activity accumulation. The levels of TNF-α and IL-6 in the serum and colon tissue of mice with experimental colitis were decreased by SANG in a concentration-dependent manner in response to p65 NF-κB. The possible mechanism of protection on experimental colitis was that SANG could be through attenuating early steps of inflammation as well as decreasing the expression of NF-κB and subsequent pro-inflammatory cytokines production.
Natural products in treatment of ulcerative colitis and peptic ulcer
2013, Journal of Saudi Chemical Society
Citation Excerpt :
In addition D-002 was effective to protect or prevent the damage associated to acetic acid-induced colitis. Upon oral administration of D-002 at doses 25 and 50 mg/kg in both single and repeated experiments, it significantly reduced the wet weight, macroscopic injury; polymorphonuclear infiltration and wall thickness in colonic mucosa of treated animals compared with the controls in both protective and therapeutic alternatives (Noa et al., 2000). Plants with antiulcerogenic activity were used either as raw materials which obtained by extraction with solvents or as individual isolated compounds.
Ulcerative colitis is an inflammatory chronic disease that affects the mucosa and submucosa of the colon and rectum. Several types of drugs are available such as aminosalicylates. Peptic ulcer disease (PUD) is a common disorder that affects millions of individuals worldwide and it can be considered one of the most important common diseases in the world. Treatment of peptic ulcers depends on using a number of synthetic drugs that reduce the rate of stomach acid secretion (Antiacids), protect the mucous tissues that line the stomach and upper portion of the small intestine (Demulcents) or to eliminate Helicobacter pylori (H. pylori). In most cases, incidence of relapses and adverse reactions is seen in the following synthetic antiulcer therapy. Accordingly, the main concern of the current article is to introduce a safe drug (or more) of natural origin, to be used for the management of gastric ulcers without side effects.
A widespread search has been launched to identify new anti-ulcer therapies from natural sources. Herbs, medicinal plants, spices, vegetables and crude drug substances are considered to be a potential source to control various diseases including gastric ulcer and ulcerative colitis. In the scientific literature, a large number of medicinal plants and their secondary metabolites with potential anti-ulcer (anti-peptic ulcer and antiulcerative colitis) activities have been reported. Treatment with natural products produces promising results and fewer side effects. Our goal is to collect the published data in the last 24 years and reviews the natural products reported in the treatment of these diseases and their mechanism of action.
Proglumide attenuates experimental colitis in rats
2005, Experimental and Toxicologic Pathology
Ulcerative colitis is associated with altered contractile activity and transit time of colon. On the other hand, cholecystokinin (CCK) has been shown to play an important role in regulation of gastrointestinal motor function including colonic contraction and transit. In the present study, an attempt was made to study the effect of proglumide, a CCK receptor antagonist on experimental colitis in rats. Experimental colitis was induced in male Sprague–Dawley rats by instilling 1 ml of 4% acetic acid followed by flushing with 0.5 ml air. The rats were kept in a head-down position for 30 s. Finally, each rat received 1.5 ml colonic wash with 1.5 ml saline. Four groups of rats received proglumide orally (0, 250, 500 and 1000 mg/kg). The first dose of proglumide was given 1 h before acetic acid challenge, whereas the second dose of proglumide was given 25 h after the first dose. Sham control rats received an equal volume of saline instead of acetic acid. Forty-eight hours after the acetic acid challenge, the colon was removed, weighed and split longitudinally and scored for injury. Part of the colon was used for histopathological study as well as analysis of myeloperoxidase (MPO) activity (as a marker of neutrophil activity). Acetic acid produced severe diarrhea and exfoliation of the colonic epithelium accompanied by extensive destruction of the mucosal interstitium. Proglumide dose dependently protected rats against acetic acid-induced increase in colon weight, diarrhea, MPO activity and colonic injury. Inhibition of CCK exerts a beneficial effect in experimental colitis. Further studies are warranted to determine the mechanism of protection and the therapeutic potential of CCK inhibitors.
Oxytocin ameliorates oxidative colonic inflammation by a neutrophil-dependent mechanism
2005, Peptides
Oxytocin (OT), a nonapeptide produced in the paraventricular and the supraoptical nuclei in the hypothalamus has a wide range of effects in the body. However, the role of OT on the gastrointestinal (GI) tract has to be settled. OT may participate in the regulation of motility, secretion, blood flow, cell turnover and release of neurotransmitters and/or peptides in the GI tract, possesses antisecretory and antiulcer effects, facilitates wound healing and is involved in the modulation of immune and inflammatory processes. The present work was conducted to assess the possible therapeutic effects of OT against the acetic acid-induced colonic injury in the rat. Methods: Colitis was induced by intracolonic administration of acetic acid (5%) in Sprague–Dawley rats (200–250 g). Either saline or OT (0.5 mg/kg) was injected subcutaneously, immediately after the induction of colitis and repeated two times a day for 4 days. On the 4th day, rats were decapitated and distal 8 cm of the colon were removed for the macroscopic and microscopic damage scoring, determination of tissue wet weight index (WI), malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Colonic collagen content, as a fibrosis marker was also determined. Lactate deydrogenase (LDH) and tumor necrosis factor-alpha (TNF-α) levels were assayed in serum samples. In the acetic acid-induced colitis, macroscopic and microscopic damage scores, WI, MDA and MPO levels were significantly increased, while GSH levels were decreased when compared to control group (p < 0.05–<0.001). Treatment with OT abolished the colitis-induced elevations in damage scores, WI, MDA and MPO levels and restored the GSH levels (p < 0.05–0.001). Similarly, acetic acid increased the collagen content of colonic tissues and OT-treatment reduced this value to the level of the control group. Serum LDH and TNF-α levels were also elevated in the acetic acid-induced colitis group as compared to control group, while this increase was significantly decreased by OT treatment. The results suggest that OT, which improves the antioxidative state of the colonic tissue and ameliorates oxidative colonic injury via a neutrophil-dependent mechanism, requires further investigation as a potential therapeutic agent in colonic inflammation.
Protective effect of Copaifera langsdorffii oleo-resin against acetic acid-induced colitis in rats
2004, Journal of Ethnopharmacology
The oleo-resin from Copaifera langsdorffii (Leguminosae) was evaluated in rats on acetic acid-induced colitis. Rats were pretreated orally (15 and 2 h) or rectally (2 h) before the induction of colitis with copaiba oleo-resin (200 and 400 mg/kg) or vehicle (1 ml, 2% Tween 80). Colitis was induced by intracolonic instillation of a 2 ml of 4% (v/v) acetic acid solution and 24 h later, the colonic mucosal damage was analyzed for the severity of macroscopic colonic damage, myeloperoxidase (MPO) activity, and malondialdehyde levels. A significant reduction in gross damage score and in wet weight/length ratio of colonic tissue were evident in test substance-pretreated animals as compared to vehicle or oleo-resin alone-treated controls. This effect was confirmed biochemically by a reduction in colonic myeloperoxidase activity, the marker of neutrophilic infiltration, and by a marked decrease in malondialdehyde level, an indicator of lipoperoxidation. Furthermore, microscopical examination revealed the diminution of inflammatory cell infiltration, and submucosal edema in the colon segments of rats treated with copaiba oleo-resin. The data indicate the protective effect of copaiba oleo-resin in the animal model of acute colitis possibly through an antioxidant and or anti-lipoperoxidative mechanism.

View all citing articles on Scopus

^☆: Unspecified

View full text

Regular ArticleEFFECT OF D-002 ON ACETIC ACID-INDUCED COLITIS IN RATS AT SINGLE AND REPEATED DOSES☆

Abstract

Prostagland Leukotrienes Essent Fatty Acids

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Anti-ulcer activity of higher primary alcohols of beeswax

J Pharm Pharmacol

Possible mechanism cytoprotective of D-002

J Pharm Pharmacol

Acetic acid-induced colitis in normal and essential fatty acid deficient rats

J Pharmacol Exp Ther

Effect of D-002 on the pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea pig

J Pharm Pharmacol

Regular Article
EFFECT OF D-002 ON ACETIC ACID-INDUCED COLITIS IN RATS AT SINGLE AND REPEATED DOSES☆