Influence of rhein anthrone on peristaltic reflex of guinea‐pig isolated ileum: involvement of prostaglandins

Nijs, Greg; Witte, Peter de; Geboes, Karel; Meulemans, Ann; Schuurkes, J. A. J.; Lemli, J

doi:10.1111/j.1476-5381.1993.tb13473.x

Cited by 8 publications

(5 citation statements)

References 19 publications

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“…Apopto sis of damaged small and large intestinal epi thelial cells is followed by shedding of these cells into the lumen (rat) or by phagocytosis of the apoptotic cell bodies by macrophages (guinea pig and probably man) [1][2][3]. The last condition is associated with pseudomelanosis or pseudolipofuscinosis [4], Experimental data suggest that sennosides act at least partly through induction of release of mediators, especially prostaglandins [5,6]. Prostaglandins of the E series have several effects upon the gastrointestinal mucosa in cluding a 'cytoprotective' effect but also a tro phic effect increasing gastric mucosal cell pro duction [7][8][9][10], A weak proliferative response in the colon has also been reported [11].…”

Section: Introductionmentioning

confidence: 99%

Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation

Nijs

Mengs²,

Geboes

et al. 1993

Pharmacology

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Experimental studies indicate that laxatives may induce epithelial damage. In addition, some laxatives induce the release of prostaglandins. Epithelial cell damage and release of prostaglandins are two pathways by which epithelial cell proliferation could be influenced. Furthermore, fermentable laxatives like lactulose may influence large intestine cell proliferation by the trophic effect of the fermentation products such as short-chain fatty acids. For these reasons an in vivo study in rats was performed to compare the short- and long-term effect of sennosides, bisacodyl, sodium picosulfate and lactulose on epithelial cell proliferation in the ileum and large intestine. Cell proliferation was examined by the BrdUrd labelling technique after 2, 6 and 12 weeks of continuous treatment. Studies in control animals show that the Labeling Index (LI) is higher in the cecum compared with other segments of the colon, and higher in the ileum than in the colon. Treatment with sennosides, bisacodyl and sodium picosulfate does not influence the LI in the ileum and induces no statistically significant increase of the LI when the treated groups are compared with the control group. The proliferative pattern along the crypts remains unchanged with all the laxatives throughout the study. It appears therefore that ‘contact’ laxatives have no major influence on ileal and colonic epithelial cell proliferation and should not be regarded as tumor-promoting substances.

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Section: Introductionmentioning

confidence: 99%

Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation

Nijs

Mengs²,

Geboes

et al. 1993

Pharmacology

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“…It is also well known that rhein, an active metabolic product derived from microbial fermentation of the natural occurring sennosides, induces motor changes in the colon resulting in a faster passage of faeces (Capasso & Gaginella, 1997). However, only recently it has been demonstrated in vitro that sennosides derivatives increase circular muscle contractility (Rumsey et al , 1993) and peristalsis (Nijs et al , 1993), but it is not clear if this effect is due to a direct action on circular muscle, to activation of circular muscle motorneurons or to a multisynaptic pathways involving nicotinic synapses.…”

Section: Discussionmentioning

confidence: 99%

“…Rhein affects intestinal peristalsis in the guinea‐pig isolated ileum (Nijs et al , 1993). Peristalsis involves two polarized reflexes, the ascending contraction and descending relaxation, which both move aborally and thus propel the intraluminal content (Furness & Costa, 1987).…”

Section: Discussionmentioning

confidence: 99%

“…This is probably due to the difficulty to reproduce in vitro their stimulating effect on intestinal motility observed in vivo (Leng‐Peschlow, 1992). Indeed previous studies in vitro have documented that rhein decreases intestinal contractility in the rat intestine (Odenthal & Ziegler, 1988), but recently it has been shown that increased intestinal peristalsis in the guinea‐pig ileum (Nijs et al , 1993) and increased circular smooth muscle contractility in the rat intestine is produced by sennoside aglycones (Rumsey et al , 1993). However, it is still not clear whether sennosides derivatives act on smooth muscle, nerves or via activation of intrinsic reflexes.…”

Section: Introductionmentioning

confidence: 99%

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Effect of sodium rhein on electrically‐evoked and agonist‐induced contractions of the guinea‐pig isolated ileal circular muscle

Izzo¹,

Mascolo²,

Capasso³

1998

British J Pharmacology

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1 This study examined the e ects of sodium rhein (0.03 ± 30 mM) on the contractions of the isolated circular muscle of guinea-pig ileum induced by acetylcholine (100 nM), substance P (3 nM) and electrical stimulation (10 Hz for 0.3 s, 100 mA, 0.5 ms pulse duration). The e ect of sodium rhein was also evaluated on the ascending excitatory re¯ex using a partitioned bath (oral and anal compartments). Ascending excitatory enteric nerve pathways were activated by electrical ®eld stimulation (10 Hz for 2 s, 20 mA, 0.5 pulse duration) in the anal compartment and the resulting contraction of the guinea-pig intestinal circular muscle in the oral compartment was recorded. 2 Sodium rhein (0.3, 3 and 30 mM) signi®cantly potentiated (52+11% at 30 mM) acetylcholine-induced contractions. In the presence of tetrodotoxin (0.6 mM) or o-conotoxin GVIA (10 nM) sodium rhein (3 and 30 mM) did not enhance, but signi®cantly reduced (49+10% and 44+8%, respectively, at 30 mM) acetylcholine-induced contractions. 3 Sodium rhein (0.3, 3 and 30 mM) signi®cantly increased (65+11% at 30 mM) substance P-induced contractions. In the presence of tetrodotoxin (0.6 mM), o-conotoxin GVIA (10 nM) or atropine (0.1 mM), sodium rhein (3 and 30 mM) signi®cantly reduced (50+10%, 55+8% and 46+10%, respectively, at 30 mM) substance P-induced contractions. 4 N G -nitro-L-arginine methyl ester (L-NAME, 100 mM) abolished the potentiating e ect of sodium rhein on acetylcholine and substance P-induced contractions. At the highest concentration (30 mM), sodium rhein, in presence of L-NAME, reduced the acetylcholine (30+6%)-or substance P (36+6%)-induced contractions. 5 Sodium rhein (30 mM) signi®cantly potentiated (29+9%) the electrically-evoked contractions. L-NAME (100 mM), but not phentolamine, enhanced the e ect of sodium rhein. Sodium rhein (30 mM) signi®cantly increased (32+9%) the ascending excitatory re¯ex when applied in the oral, but not in the anal compartment. 6 These results indicate that sodium rhein (i) activates excitatory cholinergic nerves on circular smooth muscle presumably through a facilitation of Ca 2+ entry through the N-type Ca 2+ channel, (ii) has a direct inhibitory e ect on circular smooth muscle and (iii) does not a ect enteric ascending neuroneural transmission. Nitric oxide could have a modulatory excitatory role on sodium rhein-induced changes of agonist-induced contractions and an inhibitory modulator role on sodium rhein-induced changes of electrically-induced contractions.

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“…The influence on secretion and motility has clearly been ob served in in vivo experiments but it has thus far been difficult to demonstrate the effect on motility in in vitro conditions. This has recent ly been done, however, with a modified Tren delenburg technique when the drug was ap plied to the mucosal side [2], Further experi mental evidence suggests that an intact mucosa is essential for the laxative effect of rhein anthrone, the active component of sennosides.…”

Section: Introductionmentioning

confidence: 99%

Anthranoids and the Mucosal Immune System of the Colon

et al. 1993

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The mechanism of action of anthranoids in general and of sennosides at the cellular level is not precisely known. Pseudomelanosis or pseudolipofuscinosis, a condition characterized by the accumulation of pigmented macrophages in the lamina propria, is one of the well-known effects of these products. It is most probably the result of an interaction between apoptotic epithelial cells and the lamina propria cellular infiltrate. Treatment of cell suspensions of intestinal epithelial cells and of human intestinal epithelial cells in culture with rhein anthrone, the active compound of sennosides, demonstrates a direct influence of the drug on these epithelial cells. Low doses induce alterations in cellular shape and organelles consistent with increased metabolism. High doses induce apoptotic changes. The interaction between the epithelial cells and cells of the monocyte/macrophage lineage induces also the release of prostaglandins of the E series as shown by experiments on cell cultures of epithelial cells and peripheral blood cells. An increase of PGE2 release to about 140% of the control value is noted following administration of low doses of rhein anthrone to a combination of human intestinal epithelial cells and human peripheral blood mononuclear cells. This finding indicates that rhein anthrone is activating cellular components of the intestinal immune system and may by this pathway induce secretion and motility.

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Influence of rhein anthrone on peristaltic reflex of guinea‐pig isolated ileum: involvement of prostaglandins

Cited by 8 publications

References 19 publications

Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation

Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation

Effect of sodium rhein on electrically‐evoked and agonist‐induced contractions of the guinea‐pig isolated ileal circular muscle

Anthranoids and the Mucosal Immune System of the Colon

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Influence of rhein anthrone on peristaltic reflex of guinea‐pig isolated ileum: involvement of prostaglandins

Cited by 8 publications

References 19 publications

Effects of &lsquo;Contact Laxatives&rsquo; on Intestinal and Colonic Epithelial Cell Proliferation

Effects of &lsquo;Contact Laxatives&rsquo; on Intestinal and Colonic Epithelial Cell Proliferation

Effect of sodium rhein on electrically‐evoked and agonist‐induced contractions of the guinea‐pig isolated ileal circular muscle

Anthranoids and the Mucosal Immune System of the Colon

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Product

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Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation

Effects of ‘Contact Laxatives’ on Intestinal and Colonic Epithelial Cell Proliferation