Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry and AngII reactivity in a rat model of DM. Streptozotocin (STZ, 55 mg/kg) was administered to induce DM to 24 adult male Wistar rats. Diabetic rats displayed all the characteristic signs of type 1 DM (T1DM) and fecal excretion increased about 4-fold over 14 days, while the excretion of controls remained unaltered. Compared to controls, diabetic ileum and colon presented an increase in both macroscopic (length, perimeter and weight) and microscopic (muscular wall thickness) parameters. Functionally, AngII-induced smooth muscle contraction was lower in diabetic rats, except in the distal colon. These differences in the contractile response to AngII may result from an imbalance between AngII type 1 (antagonized by candesartan, 10 nM) and type 2 receptors activation (antagonized by PD123319, 100 nM). Taken together, these results indicate that an early and refined STZ-induced T1DM rat model already shows structural remodelling of the gut wall and decreased contractile response to AngII, findings that may help to explain diabetic dysmotility.

Interaction between the Renin-Angiotensin System and Enteric Neurotransmission Contributes to Colonic Dysmotility in the TNBS-Induced Model of Colitis.

Angiotensin II (Ang II) regulates colon contraction, acting not only directly on smooth muscle but also indirectly, interfering with myenteric neuromodulation mediated by the activation of AT1 /AT2 receptors. In this article, we aimed to explore which mediators and cells were involved in Ang II-mediated colonic contraction in the TNBS-induced rat model of colitis. The contractile responses to Ang II were evaluated in distinct regions of the colon of control animals or animals with colitis in the absence and presence of different antagonists/inhibitors. Endogenous levels of Ang II in the colon were assessed by ELISA and the number of AT1/AT2 receptors by qPCR. Ang II caused AT1 receptor-mediated colonic contraction that was markedly decreased along the colons of TNBS-induced rats, consistent with reduced AT1 mRNA expression. However, the effect mediated by Ang II is much more intricate, involving (in addition to smooth muscle cells and nerve terminals) ICC and EGC, which communicate by releasing ACh and NO in a complex mechanism that changes colitis, unveiling new therapeutic targets.

2,4,6-trinitrobenzenesulfonic acid-induced colitis in Rattus norgevicus: a categorization proposal.

Reproducibility in animal research is crucial for its reliance and translational relevance. The 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced model of inflammatory bowel disease (IBD) is widely used but inconsistently and incompletely characterized throughout the literature. This hinders comparisons between studies and influences the low rate of translation of effective preclinical molecules. The purpose of this study was to categorize TNBS-induced colitis, based on macroscopic and microscopic scoring systems, and to identify basic routine parameters that could anticipate those categories. We retrospectively analysed male Wistar Rattus norvegicus (n=28 for the control group and n=87 for the TNBS group) and categorized TNBS-induced colitis in three phenotypes: Mild, Moderate and Severe colitis, as for human IBD. Also, we showed that the time course of food intake and fecal excretion (but not body weight, fluid intake or welfare scores) could foresee those categories. So, routine evaluation of food intake and fecal excretion may guide researchers in planning their experiments, selecting the animals with the severity of colitis that better matches their aims, or applying early humane endpoints to animals that will not be used in the experiments. In conclusion, categorizing TNBS-induced colitis enhances the reproducibility of data gathered with this experimental model and strengths its translational relevance.

Characterization of ethyl acetate and n-butanol extracts of Cymbopogon schoenanthus and Helianthemum lippii and their effect on the smooth muscle of the rat distal colon.

ETHNOPHARMACOLOGY RELEVANCE: Cymbopogon schoenanthus (C. schoenanthus) and Helianthemum lippii (H. lippii) are Saharan species found in the South West of Algeria, in the region of Bechar. Both plants are used in traditional medicine to treat gastrointestinal disorders. OBJECTIVE: The aim of our study was to characterize the composition of the ethyl acetate (EtOAc) and n-Butanol (n-BuOH) extracts of C. schoenanthus and H. lippii, and to elucidate and compare their effect on the reactivity of the rat distal colon. MAIN METHODS: The plants were macerated in a hydroalcoholic solution. After concentration, the aqueous solutions of the residues were submitted to liquid-liquid extractions to obtain EtOAc and n-BuOH extracts. The phenolic and flavonoid content of the extracts was determined by high performance liquid chromatography coupled with mass spectrometry with a time of flight analyzer (HPLC-TOF/MS). The effect of the extracts was tested on the rat distal colon, namely on the basal tone and on KCl- and Ach-induced precontracted preparations. RESULTS: HPLC-TOF/MS identified 32 phenols and flavonoids in the extracts. The four extracts relaxed the rat distal colon, the effect being noticed on the basal tone and on the KCl- and Ach-induced precontractions. The EtOAc and the n-BuOH extracts of H. lippii decreased the basal tone of the rat distal colon more markedly than the correspondent extracts of C. schoenanthus. Moreover, the n-BuOH extract of C. schoenanthus decreased the basal tone more markedly than the EtOAc extract of this plant but there was no difference between extracts of H. lippii. The EtOAc extracts of both C. schoenanthus and H. lippii totally reverted both the KCl- and the Ach-induced precontraction of the rat distal colon. However, the n-BuOH extracts of the two plants reverted the Ach-precontracted colon but not the colon that has been precontracted with KCl. CONCLUSION: Extracts of H. lippii contain a higher level of phenols compared to the extracts of C. schoenanthus. All extracts of C. schoenanthus and H. lippii caused marked relaxation of the isolated rat distal colon, either when applied directly or when tested over KCl- and Ach-induced precontraction. These results give support to the use of C. shoenanthus and H. lippii in traditional medicine, namely for gastrointestinal diseases.