Experimental oesophagitis in the rat is associated with decreased voluntary movement

Abstract

Growing interest has arisen regarding the mechanism of dyspeptic symptom generation. However, no evaluation system of these symptoms in animals has been developed. In this study, we examined whether voluntary movement of rats could be a measure to assess visceral symptoms of reflux oesophagitis. A chronic acid reflux oesophagitis model was made using rats, and the size of erosions was measured. Omeprazole was administered to the oesophagitis rats for 10 days. The amount of voluntary movement was measured by an infrared sensor. Intracellular spaces in oesophageal epithelium were also measured using a emission electron microscope. NP-40 soluble and insoluble fractions of claudins were examined by Western blot. Voluntary movement was significantly lower in the oesophagitis model rats than in the sham-operated rats (P < 0.01). Although omeprazole reduced the size of erosions, it did not significantly affect the total amount of voluntary movement (r = -0.033, P = 0.916). Intracellular spaces were significantly dilated in the oesophagitis model rats and claudin-3 showed a significantly lower relative quantity in the NP-40 insoluble fraction. Omeprazole significantly increased voluntary movement of oesophagitis model rats and the relative quantity of claudin-3 in the insoluble fraction (P < 0.05). Dilated intercellular spaces and the lower level of claudin-3 may relate to the voluntary movement of oesophagitis model rats. Decreases in voluntary movement of oesophagitis model rats may reflect visceral symptoms and be able to serve as an index of chronic abdominal symptoms.

Acid modulates the squamous epithelial barrier function by modulating the localization of claudins in the superficial layers

“…21 Claudin-1 was visualized predominantly in the suprabasal cell layers as a line, in contrast to the intense dot localization of occludin, ZO-1 or claudin-4 detected in the superficial layers. Although claudin-3 has been detected in rat esophagus 6 and claudin-18 has been detected in Barrett's esophageal epithelia, claudin-3 and claudin-18 were not detected in our normal human esophagus or ALI-cultured NHBE cells (data not shown).…”

“…In both animal models and humans, dilatation of intercellular spaces (DIS) has been noted in acid-exposed tissues by means of transmission electron microscopy (TEM). [3][4][5][6] However, the mechanism responsible for the selective localization of DIS in the basal and suprabasal cell layers is still unknown. 7 Furthermore, whether DIS is related to the diffusion of hydrogen ions through esophageal epithelium is uncertain.…”

Bile salts disrupt human esophageal squamous epithelial barrier function by modulating tight junction proteins

“…In the present experiments involving acidic bile salts, the levels of claudin-1 and -4 in the insoluble fraction significantly decreased following treatment with acidic GCA or TCA. Although claudin-3 has been detected in rat esophagus and claudin-18 has been detected in Barrett's esophageal epithelia (17,23,27), claudin-3 and claudin-18 were not detected in normal human esophagus or ALI-cultured cultured HEECs. As a limitation of the present study, although we previously detected the delocalization of claudin-4 in both colonic epithelial cell model and stratified epithelial cell model with NHBE cells after stimulation (29,31), differences in the staining pattern of TJ proteins after acidic bile acid stimulation were not detected in our HEECs model.…”

Gastrointestinal mucosal barrier function and diseases

“…Complicated expression patterns of various CLDNs in different species make the data confusing. For example, CLDN3 was detected in a rat esophagus, and it has been reported to be modulated in rat esophageal disorders including reflux esophagitis [19][20][21][22]. However, CLDN3 is not detectable in the human esophagus, suggesting that, if it is expressed, it must be expressed at a very low level.…”