RESUMO
The purpose of this review, based on studies from our laboratory as well as from others, is to summarize salient features of mast cell immunobiology and to describe their associations with gastrointestinal mucosal defense. Gastrointestinal mast cells are involved in many pathologic effects, such as food hypersensitivity. On the other hand, they also play a protective role in defense against parasitic and microbial infections. Thus, they have both positive and negative effects, but presently the mechanisms that control the balance of these various effects are poorly known. It has been suggested that stabilization of mast cells may be a key mechanism to protect the gastrointestinal tract from injury. Few molecules are known to possess both mast cell stabilizing and gastrointestinal cytoprotective activity. These include zinc compounds, sodium cromoglycate, FPL 52694, ketotifen, aloe vera, certain flavonoids such as quercetin, some sulfated proteoglycans such as chondroitin sulfate and dehydroleucodine. Dehydroleucodine, a sesquiterpene lactone isolated from Artemisia douglasiana Besser, exhibits anti-inflammatory and gastrointestinal cytoprotective action. The lactone stimulates mucus production, and inhibits histamine and serotonin release from intestinal mast cells. The lactone could act as a selective mast cell stabilizer by releasing cytoprotective factors and inhibiting pro-inflammatory mast cell mediators. (AU)
Assuntos
Humanos , Sistema Digestório/citologia , Sistema Digestório/imunologia , Mastócitos/citologia , Mastócitos/imunologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Mucosa Gástrica/citologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Imunidade nas Mucosas/imunologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Lactonas/farmacologia , Lactonas/uso terapêutico , Mastócitos/efeitos dos fármacos , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêuticoRESUMO
The purpose of this review, based on studies from our laboratory as well as from others, is to summarize salient features of mast cell immunobiology and to describe their associations with gastrointestinal mucosal defense. Gastrointestinal mast cells are involved in many pathologic effects, such as food hypersensitivity. On the other hand, they also play a protective role in defense against parasitic and microbial infections. Thus, they have both positive and negative effects, but presently the mechanisms that control the balance of these various effects are poorly known. It has been suggested that stabilization of mast cells may be a key mechanism to protect the gastrointestinal tract from injury. Few molecules are known to possess both mast cell stabilizing and gastrointestinal cytoprotective activity. These include zinc compounds, sodium cromoglycate, FPL 52694, ketotifen, aloe vera, certain flavonoids such as quercetin, some sulfated proteoglycans such as chondroitin sulfate and dehydroleucodine. Dehydroleucodine, a sesquiterpene lactone isolated from Artemisia douglasiana Besser, exhibits anti-inflammatory and gastrointestinal cytoprotective action. The lactone stimulates mucus production, and inhibits histamine and serotonin release from intestinal mast cells. The lactone could act as a selective mast cell stabilizer by releasing cytoprotective factors and inhibiting pro-inflammatory mast cell mediators.
Assuntos
Humanos , Sistema Digestório , Mastócitos/citologia , Mastócitos/imunologia , Anti-Inflamatórios , Imunidade nas Mucosas/imunologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Lactonas/farmacologia , Lactonas/uso terapêutico , Mastócitos/efeitos dos fármacos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Mucosa Gástrica/citologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêuticoRESUMO
OBJECTIVE AND DESIGN: DhL, a lactone isolated from Artemisia douglasiana, prevents gastrointestinal damage elicited by necrosis-inducing agents and exhibits antiinflammatory action. This work examines the effect of DhL on compound 48/80-induced histamine and serotonin release in the isolated mouse jejunum, to determine whether DhL inhibits mediator release from mast cells at the enteric level. MATERIAL: Thirty jejuna from male Balb-c mice were used for the studies. TREATMENT: Samples were incubated sequentially in 9 test tubes containing RBS or 10 microg/ml compound 48/80 or 1.6 mmol/l + 10 microg/ml compound 48/80 at 37 degrees C for 90 minutes (10 min per tube). METHODS: Histamine and serotonin release studies, quantification of granulated mast cells, and evaluation of mast cell ultrastructure were carried out. Differences between groups were determined using analysis of variance followed by Tukey-Kramer multiple comparisons test. RESULTS: Compound 48/80 increased histamine and serotonin release by the tissue (141.95 +/- 62.58 pg/mg tissue vs basal 5.45 +/- 1.04, P<0.01 and 20.04 +/- 2.81 vs basal 9.24 +/- 1.56 ng/ mg tissue, P<0.01, respectively), decreased the number of granulated submucosal mast cells (0.077 +/- 0.0035 vs basal 0.14 +/- 0.015, P<0.05), and elicited evident granule ultrastructural changes. These effects were reduced by dehydroleucodine (19.51 +/- 7.88, P<0.01; 12.69 +/- 1, P<0.05 and 0.143 +/- 0.014, P<0.05, respectively). CONCLUSION: The lactone inhibits compound 48/80-induced histamine and serotonin release from mast cells in the isolated mouse jejunum.
Assuntos
Antiulcerosos/farmacologia , Histamina/metabolismo , Jejuno/metabolismo , Lactonas/farmacologia , Mastócitos/metabolismo , Serotonina/metabolismo , Sesquiterpenos/farmacologia , Animais , Antagonistas dos Receptores Histamínicos H1/farmacologia , Processamento de Imagem Assistida por Computador , Técnicas In Vitro , Jejuno/citologia , Jejuno/efeitos dos fármacos , Cetotifeno/farmacologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica , Microscopia de Vídeo , p-Metoxi-N-metilfenetilamina/farmacologiaRESUMO
Changes in the morphology of viscacha Sertoli cells were studied during the annual reproductive cycle. Sertoli cells exhibited marked nuclear and cytoplasmic changes. Seasonal variation in nuclear size and shape, chromatin texture, and nucleolus characteristics was observed. The seasonal patterns of the volume densities of the endoplasmic reticulum (ER), mitochondria, Golgi complex, dense bodies and lipid inclusions were distinct. Morphometric analysis revealed that the Golgi complex is the organelle most sensitive to seasonal change. It declined drastically in the regressed testes and its recovery was slow. The ER and mitochondria exhibited seasonal variations in their pattern and content, that was minimal during winter. In contrast, an accumulation of lipid and dense bodies, such as primary and secondary lysosomes, accompanied the spermatogenic arrest. The volume densities of both organelles were maximum during the restoration of spermatogenesis. The length and organization of the inter-Sertoli junctions also changed with the reproductive cycle. The Sertoli cell number per tubular cross section decreased significantly during the testicular regression, coincident with the presence of Sertoli cells with marked signs of involution. The degree of regression and recovery exhibited by the viscacha Sertoli cells was closely related to that shown by the associated germ cells. Therefore, seasonal endocrine fluctuations and local factors could be involved in the regulation of the morphological and functional characteristics of the viscacha Sertoli cells. These hormonal fluctuations are synchronized by the photoperiod through the pineal gland and its hormone, melatonin.
Assuntos
Reprodução/fisiologia , Roedores/anatomia & histologia , Estações do Ano , Células de Sertoli/ultraestrutura , Animais , Contagem de Células , Masculino , Microscopia Eletrônica , Organelas/metabolismo , Organelas/ultraestrutura , Roedores/metabolismo , Células de Sertoli/metabolismoRESUMO
Randomly distributed extracellular colloidal accumulations were observed in the pars distalis of viscacha (Lagostomus maximus maximus). They were preferentially located in the peripheral zone of the gland and showed variability in shape and size. Two different types of colloidal accumulations were found by electron microscopy: 1) those surrounded by nongranulated follicular cells that correspond to characteristic follicles, and 2) those surrounded by granulated cells. In the follicles lined by nongranulated follicular cells, long, prominent microvilli and cytoplasmic processes protruded into the lumen. The frequency of these accumulations varies during the year in adult male animals, showing an increase in number during summer and a decrease during winter. The lowest value was registered in August (winter). The mean follicular diameter did not vary seasonally. The number of colloidal accumulations did not vary seasonally in adult female viscachas, but a significant difference in the mean follicular diameter between pregnant and non-pregnant females was observed. Pituitaries of immature animals contain fewer colloidal accumulations than those of adults. In fetuses, these accumulations were absent. The administration of melatonin provoked a decrease in the number of these structures. The numeric changes of the colloidal accumulations observed in this study are associated with: 1) the seasonal reproductive activity in adult males, and 2) the reproductive condition, body weight and sexual maturity in males and females. The fact that melatonin administration decreases the population of colloidal accumulations in males suggests participation of the pineal gland in these changes.
Assuntos
Hipófise/crescimento & desenvolvimento , Hipófise/fisiologia , Roedores/fisiologia , Estações do Ano , Fatores Etários , Animais , Peso Corporal , Coloides/análise , Feminino , Masculino , Melatonina/farmacologia , Microscopia Eletrônica , Neurônios/efeitos dos fármacos , Neurônios/ultraestrutura , Hipófise/ultraestrutura , Gravidez , Fatores SexuaisRESUMO
We have demonstrated that dehydroleucodine (DhL), a lactone isolated from Artemisia douglasiana Besser, prevents gastroduodenal damage induced by necrosis-inducing agents such as absolute ethanol. We have also reported, in a qualitative study, that this effect is related to the ability of the drug to stimulate mucus production. The present study was designed to quantitatively evaluate the effect of DhL on adherent mucus layer thickness, to obtain a more objective approach to the mechanism of action of the drug. Mice were divided into two groups: (I) controls were treated with orally administered carboxymethylcellulose (CMC) and (II) experimental animals received DhL in CMC. The thickness of the mucus gel layer was measured in unfixed stomachs and duodena, using an image analysis system. We observed an increase in the adherent mucus layer thickness in the experimental samples. This confirms that one of the main mechanisms involved in the cytoprotective action of the drug is mucus secretion.
Assuntos
Antiulcerosos/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Lactonas/farmacologia , Muco/metabolismo , Sesquiterpenos/farmacologia , Animais , Mucosa Gástrica/metabolismo , Mucosa Intestinal/metabolismo , Masculino , CamundongosRESUMO
The adult male viscacha (Lagostomus maximus maximus) is a seasonal rodent. It exhibits a short period of testicular regression with partial arrest of spermatogenesis during winter (July-August). The present study provides the first description of the viscacha spermatogenic cycle during the period of maximum gonadal activity (summer-autumn). The testes were processed by using conventional techniques of light and electron microscopy. One-micrometer-thick sections stained with toluidine blue were used to clearly define the different cell associations. Spermatogenesis in this rodent is well organized and synchronized and has been divided into nine stages. The present classification is based on the morphogenesis of the acrosomal system (stages I-V) and the degree of elongation and condensation of the heads of the differentiating spermatids (stages VI-IX). Stage I is principally defined by round spermatids with a well-developed, juxtanuclear Golgi complex and without acrosomal components that are visible under the light microscope. Sperm release from the viscacha seminiferous epithelium occurs either in late stage III or in early stage IV. Stage IX is characterized by diplotene spermatocytes, figures of meiosis I or II, and secondary spermatocytes.
Assuntos
Roedores/fisiologia , Epitélio Seminífero/citologia , Epitélio Seminífero/fisiologia , Espermatogênese/fisiologia , Fatores Etários , Animais , Masculino , Microscopia Eletrônica , Estações do Ano , Epitélio Seminífero/ultraestrutura , Espermátides/ultraestrutura , Espermatogônias/ultraestruturaRESUMO
In previous work we have demonstrated that dehydroleucodine (DhL) prevents gastric damage induced by necrosis-inducing agents such as absolute ethanol (EtOH). In this study we examine the effects of DhL on gastroduodenal morphology and monoamine levels by histological and biochemical methods, respectively, as an approach to elucidating the cytoprotective mechanism of the drug. Histological evidence shows that DhL prevents formation of gastroduodenal mucosal lesions induced by EtOH and that this protective effect is related to the ability of the drug to stimulate mucus production. DhL itself does not affect the tissue concentration of NE, DA and 5-HT. However, it prevents the depletion of DA and 5-HT provoked by EtOH. We propose that the abundant mucoid blanket secreted after treatment with DhL acts as a diffusion barrier against EtOH. It is also possible that DhL could act as a "cell stabilizer," by inhibiting the degranulation of cells containing monoamines.
Assuntos
Antiulcerosos/farmacologia , Dopamina/fisiologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Lactonas/farmacologia , Muco/metabolismo , Norepinefrina/fisiologia , Serotonina/fisiologia , Sesquiterpenos/farmacologia , Animais , Duodeno/efeitos dos fármacos , Etanol/toxicidade , Mucosa Gástrica/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Microscopia Eletrônica de VarreduraRESUMO
The Leydig cells of viscacha (seasonal rodent) show cytoplasmic hypertrophy and regional distribution during the breeding period (summer-autumn). The dominant organelles are smooth endoplasmic reticulum (SER) and mitochondria. A moderately well-developed Golgi, abundant lipid inclusions, dense bodies like lysosomes in different stages, and centrioles are observed. Extensive or focal desmosome and gap-like junctions between neighbouring Leydig cells are present. These cells exhibit an evident hypotrophy and an increase in the number of dense bodies during the gonadal regression in winter (July and August). Cells in different stages of involution are observed in this period. Their nuclei are irregular and heterochromatic. The cytoplasm contains few mitochondria. The vesicular SER is scarse. Irregular and large intercellular spaces with microvilli and amorphous material are present. The junctional complexes are absent. The nuclear and cytoplasmic volume and development of SER and mitochondria increase during the recovery period (spring). The lipid inclusions decrease. Dilatations of the intercellular space with microvilli and limited by focal desmosome-like junctions are observed. In conclusion, the Leydig cells of Lagostomus maximus maximus show deep changes alongside the reproductive cycle. The photoperiod variations, through pineal hypothalamus pituitary axis and the hormone melatonin, are probably responsible for them. Moreover, the fall of serum and tubular testosterone would be one of the factors responsible for gonadal regression.
RESUMO
The aerial part of Artemisia douglasiana Besser (6) has been used in folk medicine as a cytoprotective agent against the development of peptic ulcer. The dehydroleucodine (DhL), its active principle, significantly prevents the formation of gastric lesions induced by the exposure of the rats to absolute ethanol orally administered. The stomachs of control and experimental rats (after ethanol and pretreated with DhL) were removed, opened along the greater curvature and studied under stereo microscope and with light and scanning electron microscope. Absolute ethanol produced focal visible hemorrhagic lesions, extensive hyperemia, vascular stasis, cell disruption, and necrosis of the mucosa. Abundant mass of mucus was observed with scanning. The stomachs of rats pretreated with DhL showed a reduction of lesions. No hemorrhage and hyperemia were observed. The epithelia of the mucosa had a cobblestone appearance, similar to control rats and was covered by a fine layer of mucus. The mechanism of the protective action of DhL is unknown although it seems to be related to endogenous prostaglandins (PG).
Assuntos
Antiulcerosos/farmacologia , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Animais , Mucosa Gástrica/patologia , Mucosa Gástrica/ultraestrutura , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/prevenção & controle , Masculino , Microscopia Eletrônica de Varredura , Necrose , Plantas Medicinais , Ratos , Ratos WistarRESUMO
The aerial part of Artemisia douglasiana Besser (6) has been used in folk medicine as a cytoprotective agent against the development of peptic ulcer. The dehydroleucodine (DhL), its active principle, significantly prevents the formation of gastric lesions induced by the exposure of the rats to absolute ethanol orally administered. The stomachs of control and experimental rats (after ethanol and pretreated with DhL) were removed, opened along the greater curvature and studied under stereo microscope and with light and scanning electron microscope. Absolute ethanol produced focal visible hemorrhagic lesions, extensive hyperemia, vascular stasis, cell disruption, and necrosis of the mucosa. Abundant mass of mucus was observed with scanning. The stomachs of rats pretreated with DhL showed a reduction of lesions. No hemorrhage and hyperemia were observed. The epithelia of the mucosa had a cobblestone appearance, similar to control rats and was covered by a fine layer of mucus. The mechanism of the protective action of DhL is unknown although it seems to be related to endogenous prostaglandins (PG).
RESUMO
The aerial part of Artemisia douglasiana Besser (6) has been used in folk medicine as a cytoprotective agent against the development of peptic ulcer. The dehydroleucodine (DhL), its active principle, significantly prevents the formation of gastric lesions induced by the exposure of the rats to absolute ethanol orally administered. The stomachs of control and experimental rats (after ethanol and pretreated with DhL) were removed, opened along the greater curvature and studied under stereo microscope and with light and scanning electron microscope. Absolute ethanol produced focal visible hemorrhagic lesions, extensive hyperemia, vascular stasis, cell disruption, and necrosis of the mucosa. Abundant mass of mucus was observed with scanning. The stomachs of rats pretreated with DhL showed a reduction of lesions. No hemorrhage and hyperemia were observed. The epithelia of the mucosa had a cobblestone appearance, similar to control rats and was covered by a fine layer of mucus. The mechanism of the protective action of DhL is unknown although it seems to be related to endogenous prostaglandins (PG).
RESUMO
The aerial part of Artemisia douglasiana Besser (6) has been used in folk medicine as a cytoprotective agent against the development of peptic ulcer. The dehydroleucodine (DhL), its active principle, significantly prevents the formation of gastric lesions induced by the exposure of the rats to absolute ethanol orally administered. The stomachs of control and experimental rats (after ethanol and pretreated with DhL) were removed, opened along the greater curvature and studied under stereo microscope and with light and scanning electron microscope. Absolute ethanol produced focal visible hemorrhagic lesions, extensive hyperemia, vascular stasis, cell disruption, and necrosis of the mucosa. Abundant mass of mucus was observed with scanning. The stomachs of rats pretreated with DhL showed a reduction of lesions. No hemorrhage and hyperemia were observed. The epithelia of the mucosa had a cobblestone appearance, similar to control rats and was covered by a fine layer of mucus. The mechanism of the protective action of DhL is unknown although it seems to be related to endogenous prostaglandins (PG).
RESUMO
The aerial part of Artemisia douglasiana Besser (6) has been used in folk medicine as a cytoprotective agent against the development of peptic ulcer. The dehydroleucodine (DhL), its active principle, significantly prevents the formation of gastric lesions induced by the exposure of the rats to absolute ethanol orally administered. The stomachs of control and experimental rats (after ethanol and pretreated with DhL) were removed, opened along the greater curvature and studied under stereo microscope and with light and scanning electron microscope. Absolute ethanol produced focal visible hemorrhagic lesions, extensive hyperemia, vascular stasis, cell disruption, and necrosis of the mucosa. Abundant mass of mucus was observed with scanning. The stomachs of rats pretreated with DhL showed a reduction of lesions. No hemorrhage and hyperemia were observed. The epithelia of the mucosa had a cobblestone appearance, similar to control rats and was covered by a fine layer of mucus. The mechanism of the protective action of DhL is unknown although it seems to be related to endogenous prostaglandins (PG).
RESUMO
Seasonal changes in reproductive activity in the adult male vizcacha (Lagostomus maximus maximus), a South American rodent, were investigated. Monthly, for 2 yr, the animals were killed and decapitated during the night near their burrows in the vicinity of San Luis, Argentina. The testes, epididymides, and pineal glands were removed and used for biochemical and structural studies. Significant changes associated with seasonal cycles were found. 1) In July-August (winter in South America), a short hibernal period of sexual quiescence, decline in testicular and epididymal weights, arrest of spermatogenesis, and decrease of serum testosterone were observed. The gonads regressed during this period, with regression most pronounced in August. 2) During September-November (spring), a recovery period--without arrest of spermatogenesis--was observed, with significant expression of gonadal activity during April-May (autumn). In this season, gonadal weight was increased and spermatogenesis was complete. These results indicate an increase in sexual activity as well as in the ability to secrete testosterone. A gradual reduction of testicular activity appeared in June-July (early winter). Conversely, in this period, the pineal hydroxyindole-O-methyl transferase activity decreased in contrast to the highest values observed in winter. Our findings indicate that the male adult vizcacha under natural conditions exhibits an annual reproductive cycle. A possible relationship between increased pineal activity and gonadal regression is also suggested.
Assuntos
Epididimo/fisiologia , Roedores/fisiologia , Estações do Ano , Testículo/fisiologia , Acetilserotonina O-Metiltransferasa/metabolismo , Animais , Epididimo/anatomia & histologia , Masculino , Tamanho do Órgão , Glândula Pineal/enzimologia , Reprodução/fisiologia , Espermatogênese , Testículo/anatomia & histologia , Testosterona/sangueRESUMO
The enzymes cytochrome-c-oxidase and P-450 were measured in adrenal cortex of male adult rats, under four experimental conditions: G1, controls; G2, orchidectomized; G3, orchidectomized and treated with testosterone and G4, orchidectomized and treated with testosterone plus dexamethasone. No differences were observed in cytochrome-c-oxidase between groups G1, G2 and G4. The highest activity was found in G3, which differs significantly from the rest of the groups. No differences were observed from cytochrome P-450 between G1 and G3 groups, while G2 and G4 differ from the G1 group. These studies support new evidences for an interaction between adrenal cortex and gonads in relation to steroidogenic and respiratory activity.
Assuntos
Córtex Suprarrenal/metabolismo , Castração , Sistema Enzimático do Citocromo P-450/metabolismo , Dexametasona/farmacologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Testosterona/farmacologia , Animais , Masculino , Ratos , Ratos EndogâmicosRESUMO
The intravascular perfusion of nickel nitrate-glutaraldehyde showed a free penetration into neonatal and adult adrenal cortex. Tracer deposits were found surrounding the cortical cells without interruption; they formed a permeate network of intercommunicated intercellular spaces in connection with the vessels. No penetration of the tracer was observed between the chromaffin cells of the medulla. During the first day after birth, canalicular structures appeared among the cortical cells. In the adrenals of 4 and 7-day-old rats the lateral contacts between adjacent cells were more extensive. In 10-day-old rats nickel delimited the cellular profile, revealing numerous infolded cellular membranes. Gap and septate-like junctions were present. In the adult rats the structure of the cell membrane was unfolded. The observations made in adrenal cortex of 10 and 90-day-old rats perfused with lanthanum hydroxide were similar to those on nickel-treated material. The structural characteristics of this network of intercommunicated spaces and the attachments between cortical cells change during neonatal development, probably favoring cell interactions.