Actions of anticolitic drugs on a guinea-pig model of immune colitis

Norris, Alan; Lewis, Alan J.; Zeitlin, I. J.

doi:10.1007/bf01965153

Cited by 13 publications

(5 citation statements)

References 18 publications

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“…A severe colitis characterized by colonic ulceration, haemorrhage and evidence of crypt abscess formation was observed after 5% DNCB challenge. A frequent diarrhoea and body weight loss were prominent features of the colitis in this group, also described previously [4].…”

Section: Resultsmentioning

confidence: 56%

“…Male, Hartley guinea-pigs (170--200 g) in groups of not less than 10 were skin-sensitized to a 2.5% solution of DNCB (BDH Ltd) in ethanol and each group challenged intrarectally 7 days later with either (a) 0.25% DNCB in Orabase (Squibb Ltd), once daily for 5 days, or (b) 5% DNCB in Orabase, once daily for 3 days, as described previously [4]. Non-sensitized animals, challenged intrarectally with 5% DNCB as described in (b), above, served as controls.…”

Section: Induction Of Colitis and Collection Of Mueosamentioning

confidence: 99%

“…We have previously ShOWn that a low intrarectal dose of DNCB (0.25%) results in mild inflammatory changes, representative of early colitis [3], while a higher concentration (5%) induces severe colonic inflammation [4] and is thus a better model for the study of acute, severe colitis. Used in combination, these models allow a sequential study of the biochemical changes of the disease process in guinea-pigs.…”

Section: Introductionmentioning

confidence: 99%

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Changes in colonic tissue levels of inflammatory mediators in a guinea-pig model of immune colitis

Norris

Lewis²,

Zeitlin

1982

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An immune colitis based on a delayed-type hypersensitivity reaction was induced in dinitrochlorobenzene (DNCB)-sensitized guinea-pigs by intrarectal challenge with DNCB. A low challenge dose (0.25% DNCB) induced mild inflammatory changes in the distal colon and rectum characterized by goblet cell depletion. A higher challenge concentration (5% DNCB) resulted in severe colonic ulceration with crypt abscess formation. The inflammatory mediators, histamine, 5-hydroxytryptamine (5HT), glandular kallikrein and PGE2 were measured in freeze-dried colonic mucosae. Histamine content was three times control (p less than 0.01) in 0.25% DNCB induced colitis, although no significant change was observed in 5% DNCB challenged animals. Mucosal 5HT content was significantly reduced (p less than 0.01) after both challenges. Glandular kallikrein content did not differ from control, while PGE2 was significantly (p less than 0.05) increased at both challenge doses. The possible significance of these changes with respect to severity of inflammation and aetiology of colitis is discussed.

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Section: Resultsmentioning

confidence: 56%

Section: Induction Of Colitis and Collection Of Mueosamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Changes in colonic tissue levels of inflammatory mediators in a guinea-pig model of immune colitis

Norris

Lewis²,

Zeitlin

1982

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“…They have no proven efficacy, however, in maintenance therapy [36]. One of the enigmas of previous work done with experimental colitis models is that corticosteroids had minimal effect on colonic inflammation [3,11,13,14]. Using the dosing regimen described by Higgs et al [37], we were able to obtain significant attenuation of colonic inflammation with corticosteriods.…”

Section: Discussionmentioning

confidence: 85%

“…In general, the administration of agents clinically effective in treating ulcerative colitis (e.g. sulfasalazine or corticosteroids) to animals with various types of experimentally induced colitis has resulted in only modest attenuation of colonic inflammation [11,12] or had no effect at all [3,13,14]. Few studies [15][16][17] have specifically investigated the efficacy of these or other agents which might be effective against acetic acid induced colitis in the rat.…”

Section: Introductionmentioning

confidence: 99%

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

Fitzpatrick¹,

Bostwick²,

Renzetti³

et al. 1990

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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.

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Studies on the mechanisms of mucous cell depletion in experimental colitis

Kaftan

Wright

1989

The Journal of Pathology

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Mucous cell depletion is an important histological discriminator in favour of ulcerative colitis. The mechanism of this change was investigated in guinea pigs with experimental colitis induced by intrarectal instillation of acetic acid or dinitrochlorobenzene (DNCB) in sensitized animals. Both models showed mucous cell depletion. Increased numbers of mucous cells were flash-labelled with tritiated thymidine (3HTdR), indicating an increased pool of proliferating (oligo-) mucous cells; mucous cell production was in fact increased absolutely compared with control animals, and there was a marked increase in the rate of turnover of mucous cells. The results indicate that in colitis there is (i) increased mucous cell production and (ii) an increased rate of mucous cell turnover due to increased loss of older mucous cells. It is concluded that the disease process in experimental colitis leads to premature discharge of mucin, so that mucous cells are no longer recognizable by light microscopy. This explains the increase in mucin production in ulcerative colitis, which occurs even in the presence of significant mucous cell depletion.

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Actions of anticolitic drugs on a guinea-pig model of immune colitis

Cited by 13 publications

References 18 publications

Changes in colonic tissue levels of inflammatory mediators in a guinea-pig model of immune colitis

Changes in colonic tissue levels of inflammatory mediators in a guinea-pig model of immune colitis

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

Studies on the mechanisms of mucous cell depletion in experimental colitis

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