Bile salt stimulation of colonic epithelial proliferation. Evidence for involvement of lipoxygenase products.

DeRubertis, Frederick R.; Craven, Patricia A.; Saito, Reisuke

doi:10.1172/jci111577

Cited by 117 publications

(40 citation statements)

References 33 publications

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“…), and the colon intestine was exposed through a midline abdominal incision. Test agents were administered intracolonically as previously described in detail (1). Briefly, a 20-gauge needle was inserted into the lumen of the large intestine at the cecal junction.…”

Section: Methods Determination Ofodc and [3h]tdr Incorporation Into Cmentioning

confidence: 99%

“…Homogenates were centrifuged at 38,000 g for 20 min and the supernatants were assayed immediately. Enzyme activity was determined from the release of "4C02 from DL-[ I-'4C] ornithine as previously described (1,17). Briefly, reaction mixtures contained 0.02 mM pyridoxal phosphate, 4 mM dithiothreitol, 1 mM EDTA, 0.4 mM L-ornithine, 40 mM sodium phosphate (pH 7.2), 100 Ml of the colonic mucosal soluble fraction (l100 Mg of protein) and 0.5 MCi of DL- [1-'4C] ornithine in a final volume of 0.25 ml.…”

Section: Methods Determination Ofodc and [3h]tdr Incorporation Into Cmentioning

confidence: 99%

“…The ability of bile salts to increase the proliferative activity ofcolonic epithelium is associated with bile salt-induced release of arachidonate from colon and the conversion of arachidonate to prostaglandins (PGs) and lipoxygenase products (1). Phenidone, an antioxidant that blocks both cyclooxygenase and lipoxygenase activities, suppresses bile salt-induced increases in colonic proliferative activity and inhibits colonic prostaglandin E2 (PGE2) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) production (1). By contrast, indomethacin, which suppresses cyclooxygenase but not lipoxygenase product formation, stimulates basal proliferative activity of colonic epithelium and potentiates this response to bile salts (1).…”

Section: Introductionmentioning

confidence: 99%

“…Phenidone, an antioxidant that blocks both cyclooxygenase and lipoxygenase activities, suppresses bile salt-induced increases in colonic proliferative activity and inhibits colonic prostaglandin E2 (PGE2) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) production (1). By contrast, indomethacin, which suppresses cyclooxygenase but not lipoxygenase product formation, stimulates basal proliferative activity of colonic epithelium and potentiates this response to bile salts (1). These findings had suggested a role for release ofarachidonate and its subsequent oxygenation in the stimulation of the proliferative activity of colonic epithelium by bile salts.…”

Section: Introductionmentioning

confidence: 99%

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Role of reactive oxygen in bile salt stimulation of colonic epithelial proliferation.

Craven¹,

Pfanstiel²,

DeRubertis³

1986

J. Clin. Invest.

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151

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Our previous studies had suggested a link between bile salt stimulation of colonic epithelial proliferation and the release and oxygenation of arachidonate via the lipoxygenase pathway. In the present study, we examined the role of reactive oxygen versus end products of arachidonate metabolism via the cyclooxygenase and lipoxygenase pathways in bile salt stimulation of rat colonic epithelial proliferation. Intracolonic instillation of 5 mM deoxycholate increased mucosal ornithine decarboxylase activity and MIHthymidine incorporation into DNA. Responses to deoxycholate were abolished by the superoxide dismutase mimetic Cull (3,5 diisopropylsalicylic acid)2 (CuDIPS), and by phenidone or esculetin, which inhibit both lipoxygenase and cyclooxygenase activities. By contrast, indomethacin potentiated the response. Phenidone and esculetin suppressed deoxycholate-induced increases in prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 5,12, and 15-hydroxyeicosatetraenoic acid (HETE), whereas CuDIPS had no effect. Indomethacin suppressed only PGE2. Deoxycholate (0.5-5 mM) increased superoxide dismutase sensitive chemiluminescence 2-10-fold and stimulated superoxide production as measured by cytochrome c reduction in colonic mucosal scrapings or crypt epithelium. Bile salt-induced increases in chemiluminescence were abolished by CuDIPS, phenidone, and esculetin, but not by indomethacin. Intracolonic generation ofreactive oxygen by xanthixanthine oxidase increased colonic mucosal ornithine decarboxylase activity and V3Hjthymidine incorporation into DNA approximately twofold. These effects were abolished by superoxide dismutase. The findings support a key role for reactive oxygen, rather than more distal products of either the lipoxygenase or cyclooxygenase pathways, in the stimulation of colonic mucosal proliferation by bile salts.

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Section: Methods Determination Ofodc and [3h]tdr Incorporation Into Cmentioning

confidence: 99%

Section: Methods Determination Ofodc and [3h]tdr Incorporation Into Cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role of reactive oxygen in bile salt stimulation of colonic epithelial proliferation.

Craven¹,

Pfanstiel²,

DeRubertis³

1986

J. Clin. Invest.

Self Cite

151

View full text Add to dashboard Cite

show abstract

“…Bile salts can enhance the release of arachidonate from colonocytes and subsequently the synthesis of PGE2. This could be another explanation of the link between cell proliferation and bile acids [35]. A third effect could be on a family of enzymes within the cell membrane known as protein kinases.…”

Section: Cytotoxicity O F Bile Acidsmentioning

confidence: 99%

Role of bile acids in colorectal carcinogenesis

Nagengast

Grubben

Munster

1995

European Journal of Cancer

316

180

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Dietary factors are considered important environmental risk determinants for colorectal cancer development. Epidemiological studies have shown that a high fat (or meat) intake is associated positively and a high starch, fibre (non-starch polysaccharide), vegetable and fruit intake negatively with colorectal cancer incidence. One mechanism by which these effects are possibly exerted is through the metabolism of secondary bile acids. Secondary bile acids are formed after enzymatic deconjugation and dehydroxylation of primary bile acids in the large bowel by anaerobic bacteria. It has been shown that these compounds can have tumour-promoting capacities in animal experiments. In epidemiological studies, colonic cancer risk is related to the faecal bile acid concentration. In serum and bile of patients with colonic adenomas, more deoxycholic acid was detected than in healthy controls. Secondary bile acids are toxic to several cell systems at physiological concentrations. The exact mechanism by which these amphiphilic molecules exert their action is not well understood. It might act through membrane damage, intracellular mitochondrial action or genotoxic effects. So far the evidence that bile acids are involved in colonic carcinogenesis is largely circumstantial. It is, however, well accepted that environmental factors, such as dietary habits influence genetic susceptibility. Bile acids could play a promoting role in this process.

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