5-FU-induced gastrointestinal dysmotility outlasts intestinal mucositis.

These results suggest an important role of TNF-alpha, IL-1beta and KC in the pathogenesis of intestinal mucositis induced by CPT-11.

The aim of this study was to evaluate the protective effect of hydrogen sulfide (H 2 S) on ethanol-induced gastric lesions in mice and the influence of ATP-sensitive potassium (K ATP ) channels, capsaicin-sensitive sensory afferent neurons, and transient receptor potential vanilloid (TRPV) 1 receptors on such an effect. Saline and L-cysteine alone or with propargylglycine, sodium hydrogen sulfide (NaHS), or Lawesson's reagent were administrated for testing purposes. For other experiments, mice were pretreated with glibenclamide, neurotoxic doses of capsaicin, or capsazepine. Afterward, mice received L-cysteine, NaHS, or Lawesson's reagent. After 30 min, 50% ethanol was administrated by gavage. After 1 h, mice were sacrificed, and gastric damage was evaluated by macroscopic and microscopic analyses. L-Cysteine, NaHS, and Lawesson's reagent treatment prevented ethanol-induced macroscopic and microscopic gastric damage in a dose-dependent manner. Administration of propargylglycine, an inhibitor of endogenous H 2 S synthesis, reversed gastric protection induced by L-cysteine. Glibenclamide reversed L-cysteine, NaHS, or Lawesson's reagent gastroprotective effects against ethanol-induced macroscopic damage in a dose-dependent manner. Chemical ablation of sensory afferent neurons by capsaicin reversed gastroprotective effects of L-cysteine or H 2 S donors (NaHS or Lawesson's reagent) in ethanol-induced macroscopic gastric damage. Likewise, in the presence of the TRPV1 antagonist capsazepine, the gastroprotective effects of L-cysteine, NaHS, or Lawesson's reagent were also abolished. Our results suggest that H 2 S prevents ethanol-induced gastric damage. Although there are many mechanisms through which this effect can occur, our data support the hypothesis that the activation of K ATP channels and afferent neurons/TRPV1 receptors is of primary importance.

Background and purpose: Sildenafil is a selective inhibitor of cGMP‐specific phosphodiesterase. Sildenafil, acting via NO‐dependent mechanisms, prevents indomethacin‐induced gastropathy. Activation of ATP‐sensitive potassium channels (KATP) is involved in gastric defence. Our objective was to evaluate the role of the NO/cGMP/KATP pathway in the protective effects of sildenafil against ethanol‐induced gastric damage. Experimental approach: Rats were treated with L‐NAME (1 or 3 mg kg−1, i.p.) or with L‐arginine (200 mg kg−1, i.p.) +L‐NAME (3 mg kg−1, i.p.), the guanylate cyclase inhibitor, ODQ (10 mg kg−1, i.p.), glibenclamide (0.1, 0.3, 1 or 3 mg kg−1, i.p.) or with glibenclamide (1 mg kg−1, i.p.) + diazoxide (3 mg kg−1, i.p.). After thirty minutes, the rats received sildenafil (1 mg kg−1, by gavage), followed by intragastric instillation of absolute ethanol (4 ml kg−1) to induce gastric damage. One hour later, gastric damage (haemorrhagic or ulcerative lesions) was measured with a planimetry programme. Samples of stomach were also taken for histopathological assessment and for assays of tissue glutathione and haemoglobin. Key results: Sildenafil significantly reduced ethanol‐induced gastric damage in rats. L‐NAME alone, without L‐arginine, significantly reversed the protection afforded by sildenafil. Inhibition of guanylate cyclase by ODQ completely abolished the gastric protective effect of sildenafil against ethanol‐induced gastric damage. Glibenclamide alone reversed sildenafil's gastric protective effect. However, glibenclamide plus diazoxide did not alter the effects of sildenafil. Conclusions: Sildenafil had a protective effect against ethanol‐induced gastric damage through the activation of the NO/cGMP/KATP pathway. British Journal of Pharmacology (2008) 153, 721–727; doi:; published online 10 December 2007

Our data suggest that IL-4 participates as a pro-inflammatory cytokine in a 5-FU-induced intestinal damage model and suggests that IL-4 antagonists may be novel therapeutics for this condition.

We have investigated the antinociceptive effects of the essential oil of Ocimum gratissimum L. (Labiatae) (EOOG) in two classical models of pain in male Swiss mice (25-35 g), the writhing test and the formalin test. At doses of 30, 100 and 300 mg/kg (po), EOOG produced a dosedependent inhibition (from 58.3 ± 4.4 to 40.7 ± 6.3, 36.4 ± 3.6 and 24.6 ± 3.6, respectively; N = 8-10, P<0.05) of acetic acid-induced writhing, causing up to a ~60% inhibition at the highest dose used, comparable to that obtained with indomethacin (10 mg/kg, po). At the same doses, EOOG predominantly inhibited the late (inflammatory) phase of the formalin-induced pain response (from 59.3 ± 8.3 to 40.4 ± 4.8, 23.2 ± 2.8 and 25.3 ± 5.5, respectively; N = 6, P<0.05), with a maximal reduction of ~60% of the control, although a significant reduction of the initial (neurogenic) phase was also observed at 300 mg/kg (from 62.5 ± 6.07 to 37 ± 5.9; P<0.05). On the basis of these data, we conclude that EOOG possesses interesting antinociceptive properties in the writhing and formalin tests. Due to the relatively low toxicity of EOOG, further detailed examination is strongly indicated for a better characterization of its pharmacological properties and its potential therapeutic value.

Lactobacillus acidophilus improves the inflammatory and functional aspects of intestinal mucositis induced by 5-FU.

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