Altered Chief Cell Morphology in the Gastric Gland of Streptozotocin-Diabetic Rats

SUMMARY: Diabetes mellitus (DM) is a metabolic disorder with rising incidences worldwide. Gastric symptoms of DM have been reported, including nausea, vomiting, bloating, and epigastric pain. Moreover, acute to chronic gastritis and atrophic gastritis occur in DM can affect the chief cells of the gastric gland. Chief cells are vital because of their ability to digest and separate vitamin B12 from protein. Lack of vitamin B12 leads to impaired DNA synthesis and abnormal metabolism in red blood cells, and eventually leading to pernicious anemia. Furthermore, decreased vibratory and positional senses, numbness, ataxia with subacute combined degeneration, and dementia are present in pernicious anemic patients. Twenty-four male adult Sprague-Dawley rats were used in this study. The rats were divided into control (n = 12) and diabetic (n = 12) groups. The rats were further separated into two categories: short-term (4 weeks) and long-term (24 weeks) groups. DM model was induced by manually injecting intraperitoneally with streptozotocin in citrate buffer at a dose of 60 mg/kg body weight. The same amount of buffer was injected into the control group. After sacrifice, three regions of the stomach (the cardia, body, and pylorus) were dissected. Histopathology was performed by staining with toluidine blue. Image analysis was used to quantify the zymogen granule accumulation in chief cells. The data were compared between the control and DM rats in each period using Student's t-test. In addition, transmission electron microscopy (TEM) was also used to examine the ultrastructures. There was a significant decrease in the percentage of zymogen granules in DM rats. Under TEM, the destructions of mitochondria, rough endoplasmic reticulum, and Golgi apparatus in the DM rat were observed in the chief cells. In rats with uncontrolled diabetes, there is damage to the chief cells all over the area of the stomach, affecting digestion and malabsorption of vitamin B12. Therefore, this result helps clinicians recognize that diabetic patients with gastric symptoms may have hidden pernicious anemia.

La diabetes mellitus (DM) es un trastorno metabólico con incidencia creciente a nivel mundial. Se han informado síntomas gástricos de DM, que incluyen náuseas, vómitos, distensión abdominal y dolor epigástrico. Además, la gastritis aguda a crónica y la gastritis atrófica que ocurren en la DM pueden afectar las células principales de la glándula gástrica. Las células principales son vitales debido a su capacidad para digerir y separar la vitamina B12 de las proteínas. La falta de vitamina B12 conduce a una síntesis de ADN deteriorada y un metabolismo anormal en los glóbulos rojos, lo que eventualmente conduce a una anemia perniciosa. Además, los pacientes con anemia perniciosa presentan disminución de los sentidos vibratorio y posicional, entumecimiento, ataxia con degeneración combinada subaguda y demencia. En este estudio se usaron 24 ratas Sprague-Dawley macho adultas. Las ratas se dividieron en grupos control (n = 12) y diabéticas (n = 12). Las ratas se separaron además en dos categorías: grupos a corto plazo (4 semanas) y a largo plazo (24 semanas). El modelo de DM se indujo inyectando manualmente por vía intraperitoneal estreptozotocina en tampón de citrato a una dosis de 60 mg/kg de peso corporal. Se inyectó la misma cantidad de tampón en el grupo control. Después del sacrificio, se disecaron tres regiones del estómago (cardias, cuerpo y píloro). La histopatología se realizó mediante tinción con azul de toluidina. El análisis de imágenes se utilizó para cuantificar la acumulación de gránulos de zimógeno en las células principales. Los datos se compararon entre las ratas control y DM en cada período utilizando la prueba t de Student. Además, se utilizó microscopía electrónica de transmisión (TEM) para examinar la ultraestructura celular. Hubo una disminución significativa en el porcentaje de gránulos de zimógeno en ratas DM. Bajo TEM, se observaron en las células principales las destrucción de las mitocondrias, del retículo endoplásmico rugoso y del complejo golgiense en la rata DM. En ratas con diabetes no controlada, hay daño en las células principales de toda el área del estómago, lo que afecta la digestión y la malabsorción de vitamina B12. Por lo tanto, este resultado ayuda a los médicos a reconocer que los pacientes diabéticos con síntomas gástricos pueden tener una anemia perniciosa oculta.

The Role of Pepsin in Laryngopharyngeal Reflux / 대한이비인후과학회지

Laryngopharyngeal reflux (LPR) is a very prevalent condition with a rising incidence. The diagnosis remains challenging and often controversial because the pathophysiology of LPR is often poorly understood and there is currently no diagnostic gold standard for LPR. Pepsin is produced by gastric chief cells in zymogen form as pepsinogen, and subsequently cleaved by the hydrochloric acid in the stomach, generating active pepsin protein. Pepsin is only produced in the stomach, and thus when detected in the laryngopharynx, it can be used as a specific marker for reflux. The carcinogenic properties of the gastric contents may also lead to cancer in target organs especially considering that they do not have intrinsic protective mechanisms as found in the esophagus. Many studies have demonstrated a high prevalence of LPR in patients with laryngeal cancer, but these studies are confounded by the cofactor such as smoking and alcohol consumption. This review focuses on the current studies about pepsin as a specific marker for LPR and putative relationship between pepsin and laryngeal cancer.

A review on gastric leptin: the exocrine secretion of a gastric hormone / 대한해부학회지

A major advance in the understanding of the regulation of food intake has been the discovery of the adipokine leptin a hormone secreted by the adipose tissue. After crossing the blood-brain barrier, leptin reaches its main site of action at the level of the hypothalamic cells where it plays fundamental roles in the control of appetite and in the regulation of energy expenditure. At first considered as a hormone specific to the white adipose tissue, it was rapidly found to be expressed by other tissues. Among these, the gastric mucosa has been demonstrated to secrete large amounts of leptin. Secretion of leptin by the gastric chief cells was found to be an exocrine secretion. Leptin is secreted towards the gastric lumen into the gastric juice. We found that while secretion of leptin by the white adipose tissue is constitutive, secretion by the gastric cells is a regulated one responding very rapidly to secretory stimuli such as food intake. Exocrine-secreted leptin survives the hydrolytic conditions of the gastric juice by forming a complex with its soluble receptor. This soluble receptor is synthesized by the gastric cells and the leptin-leptin receptor complex gets formed at the level of the gastric chief cell secretory granules before being released into the gastric lumen. The leptin-leptin receptor upon resisting the hydrolytic conditions of the gastric juice is channelled, to the duodenum. Transmembrane leptin receptors expressed at the luminal membrane of the duodenal enterocytes interact with the luminal leptin. Leptin is actively transcytosed by the duodenal enterocytes. From the apical membrane it is transferred to the Golgi apparatus where it binds again its soluble receptor. The newly formed leptin-leptin receptor complex is then secreted baso-laterally into the intestinal mucosa to reach the blood capillaries and circulation thus reaching the hypothalamus where its action regulates food intake. Exocrine-secreted gastric leptin participates in the short term regulation of food intake independently from that secreted by the adipose tissue. Adipose tissue leptin on the other hand, regulates in the long term energy storage. Both tissues work in tandem to ensure management of food intake and energy expenditure.

Effects of AG60 on Gastric Chief Cells of the Mouse Implanted with Ehrlich Carcinoma Cells / 대한해부학회지

This experiment was performed to evaluate the morphological responses of the gastric epithelial cells and the gastric chief cells of the mouse inoculated with Ehrlich carcinoma cells in the inguinal area following administration of acriflavine-guanosine composition (AG60). Healthy adult ICR mice were divided into normal and experimental groups. In the experimental groups, each mouse was inoculated with 1x10(7) Ehrlich carcinoma cells subcutaneously in the inguinal area. The day following the 7th injection of saline or AG60, each mouse was injected with methyl-3H-thymidine through tail vein. Seventy minutes after the thymidine injection, gastric tissues were taken and fixed in 10% buffered neutral formalin. Deparaffinized sections were coated with autoradiographic emulsion EM-1 and dried, and then placed in a light-tight box. The number of labeled epithelial cells in the gastric mucosae were observed and calculated. And for electron microscopic observation, gastric tissues were prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide solution. The ultrathin sections were stained with uranyl acetate and lead citrate. The size of zymogen granules and mitochondria in the gastric chief cells were observed and calculated. On the autoradiographic study, number of labeled cells in the area of 3.5 mm width (6 micrometer thickness) of mouse gastric mucosae of normal control, tumor control and AG60-treated groups were 319.7+/-66.46, 343.7+/-47.72 and 102.3+/-54.99 respectively. On the electron microscopic study, the size of zymogen granule in the gastric chief cells of normal control, tumor control and AG60-treated groups were 0.74+/-0.208 micrometer, 1.18+/-0.291 micrometer and 0.97+/-0.259 micrometer, respectively. And the mitochondrial size of the gastric chief cells of normal control, tumor control and AG60-treated groups were 0.86+/-0.364 micrometer, 1.02+/-0.466 micrometer and 0.92+/-0.390 micrometer, respectively. And in the AG60 treated group, most chief cells did not show any difference in ultrastructure, except that myelin figures were more frequently observed, in comparison with that of nornmal control group. From the above results, AG60 may suppress the DNA synthesis of the gastric epithelial cells, but does not results severe fine structural defect on the gastric chief cells. These results suggest that AG60 is expected as one of the most effective anticancer drugs.

Effect of mica monomer powder on chief and parietal cells as well as G and D cells in gastric mucosa of chronic atrophic gastritis in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the regulative action of mica monomer powder preparation on the chief and parietal cells as well as G and D cells in the gastric mucosa of the experimental atrophic gastritis (CAG) rats.</p><p><b>METHODS</b>Intervention therapy was given to the experimental CAG rats at three different doses of mica monomer powder preparation to evaluate the changes of chief and parietal cells as well as G and D cells in the gastric mucosa and the histopathological changes of gastric mucosa.</p><p><b>RESULTS</b>Mica monomer powder preparation at three different doses could increase the amount of chief and parietal cells as well as G and D cells in gastric mucosa of the experimental CAG rats and alleviate and control the inflammation of gastric mucosa and the atrophy of gastric mucosa glands. Especially, better effects were shown in the mid and high dose groups.</p><p><b>CONCLUSION</b>Mica has the pharmacological action of protecting the gastric mucosa, enhancing blood flow of the gastric mucosa, and consequently improving the inflammatory responses of the gastric mucosa. One of the mechanisms is associated with promoting the secretion of gastric acid and gastric pepsin and regulating the neuroendocrine mechanism including gut hormone secretion (gastrin and somatostatin) by increasing the number of chief and parietal cells as well as G and D cells.</p>

Ultrastructural Alterations in the Gastric Chief Cells of Mouse, induced by 5-Fluorouracil or Mitomycin C / 대한해부학회지

This experiment was performed to evaluate the morphological responses of the gastric chief cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of 5-fluorouracil or mitomycin C. Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (experimental control group, 5-fluorouracil-treated group and mitomycin C-treated group). In the experimental group, 1x107 Ehrlich carcinoma cells were inoculated subcutaneously in the inguinal area. From next day after inoculations, 0.2mL of saline (experimental control group), 5-fluorouracil (30 mg/kg, 5-fluorouracil-treated group), or mitomycin C (400 microg/kg, mitomycin C-treated group) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection, animals were sacrificed. Pieces of the tissue were taken from the gastric mucosa, prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide solution. The ultrathin sections were stained with uranyl acetate and lead citrate. The size of zymogen granule and the size of the mitochondrion in the gastric chief cells were observed and compared. In the 5-fluorouracil treated group, most chief cells did not show any difference in ultrastructure, except myelin figures were more frequently observed, in comparison with those of normal control group. But in the mitomycin Ctreated group, necrotic cells were more frequently observed than in normal control and 5-fluorouracil-treated group. The size of zymogen granule in the gastric chief cells of normal control, experimental control, 5-fluorouracil-treated and mitomycin C-treated groups were 0.98 (+/-0.108)microm, 1.05 (+/-0.092)microm, 0.94 (/-0.123)microm and 0.93 (+/-0.156)microm, respectively. And the size of mitochondrion in the gastric chief cells of normal control, experimental control, 5-fluorouracil-treated and mitomycin C-treated groups were 0.80 (+/-0.130)microm, 0.83 (+/-0.143)microm, 0.87 (+/-0.165)microm and 0.81 (+/-0.083)microm, respectively. From the above results, in the treatment of low therapeutic doses of anticancer drugs into the animals inoculated with Ehrlich carcinoma cells, 5-fluorouracil may not suppress function of the gastric chief cells, but mitomycin C may exert a vicious influence on the function of the gastric chief cells.

Estudo histológico e computadorizado das áreas com células parietais e principais no estômago de ratos Wistar tratados com pantoprazol e N-Nitroso-N-Methylurea (NMU) / Histological and computer study with parietal and chief cells stomach areas in Wistar rats treated with pantoprazole and N-Nitroso-N-Methylurea (NMU)

O uso prolongado dos inibidores da bomba de prótons tem sido considerado uma condição de risco para o desenvolvimento de gastrite atrófica e tumores gástricos. Objetivo: Estudar o efeito do uso de pantoprazol (PTZ) e carcinogênese pela "N-Nitroso-N-Methylurea" (NMU), por 15 semanas, sobre o estômago glandular de ratos Wistar, pela análise histológica e computadorizada das áreas com células parietais (AP), principais (AZ) e da mucosa não oxíntica (ANO), além do estudo das alterações histopatológicas identificadas. Métodos: Quarenta ratos Wistar machos foram distribuídos em 4 grupos: G1 (controle), G2 (NMU+PTZ), G3 (PTZ) e G4 (NMU). O pantoprazol foi administrado 2x/semana (14mg/kg de peso, i.p.) e a NMU oferecida, ad libitum, diluída na água de beber (100mg/ml). Após o estudo histológico AP, AZ e ANO foram determinadas por análise computadorizada das imagens dos estômagos, utilizando o programa "ImageJ 1.19z". Resultados: Mostraram redução da AP e aumento da ANO, em G2, G3 e G4 (p<0,001). Foram encontrados casos de atrofia, inflamação aguda e inflamação crônica, em número que impediu comparação estatística entre os grupos estudados. Conclusão: O uso contínuo de pantoprazol (i.p.), por 15 semanas, reduziu a área com células parietais e aumentou a área de mucosa não oxíntica no estômago glandular de ratos Wistar machos. O mesmo aconteceu no grupo de animais que receberam NMU isoladamente ou em associação com o pantoprazol.