Anti-inflammatory effect of the hydralcoholic extract of Zingiber officinale rhizomes on rat paw and skin edema.

Plant extracts have been used for centuries as a popular mode of treatment for several health disorders. Over the last ten years, the study of those extracts has attracted attention in different fields of the biological sciences. Ginger, the rhizome of Zingiber officinale Roscoe (Zingiberaceae), is a commom constituent of diet worldwide and it has been reported that its extracts present some pharmacological activities. Here we investigate the effects of the crude hydralcoholic extract of ginger rhizomes on the classical models of rat paw and skin edema. The carrageenan-, compound 48/80- or serotonin-induced rat paw edema were inhibited significantly by the intraperitoneal administration of alcoholic ginger extract. Ginger extract was also effective in inhibiting 48/80-induced rat skin edema at doses of 0.6 and 1.8 mg/site. Rat skin edema induced by substance P or bradikinin was not affected by treatment with Z. officinalle extract. The intraperitoneal administration of ginger extract (186 mg/kg(-1) body wt.) 1 h prior to serotonin injections, reduced significantly the serotonin-induced rat skin edema. Our results demonstrated that crude extract of Zingiber officinale was able to reduce rat paw and skin edema induced by carrageenan, 48/80 compound and serotonin. The antiedematogenic activity seems to be related, at least partially, to an antagonism of the serotonin receptor.

Contribution of C-fibers to leucocyte recruitment in bronchoalveolar lavage fluid and pleural cavity in the rat.

The effect of neonatal capsaicin (8 methyl-N-vanillyl-6-nonenamide) treatment on the leucocyte infiltration into the airways and pleural cavity was investigated in rats actively sensitized with ovalbumin. The animals were neonatally injected with either capsaicin (50 mg/kg, s.c., 2nd day of life) or vehicle (10% ethanol and 10% Tween 80). At adult ages, the animals were actively sensitized with ovalbumin (200 microg, s.c.) and 14 days later they were intratracheally (or intrapleurally) challenged with ovalbumin. The substance P level in bronchoalveolar lavage fluid of the capsaicin group was reduced by >90% compared to control group (vehicle), confirming the efficacy of capsaicin treatment. In the capsaicin group, the number of neutrophils (but not of eosinophils and mononuclear cells) in bronchoalveolar lavage fluid of sensitized animals was significantly higher than the control group. Intrapleural injection of ovalbumin in sensitized rats caused a significant neutrophil influx at 6 h that was markedly increased in the capsaicin-pretreated animals compared to control group. The counts of eosinophils and mononuclear cells in the pleural exudates did not differ significantly between capsaicin and control groups. The increased levels of immunoglobulin (Ig)E, IgG1 and IgG2a anti-ovalbumin antibodies in serum of sensitized rats did not differ between capsaicin and control groups. In conclusion, the exacerbated pulmonary neutrophil recruitment caused by the capsaicin neonatal treatment is unrelated to increase in serum immunoglobulin antibodies, and suggests a protective role for C-fibers in attenuating the allergic neutrophil infiltration.

Synthesis, anti-inflammatory and antimicrobial activities of new 1,2,4-oxadiazoles peptidomimetics.

A new series of 1,2,4-oxadizoles 6a-g have been synthesised in good yields using the peptide synthesis strategy. The prepared compounds were tested for anti-inflammatory and antimicrobial activities. The anti-inflammatory activities were determined in the rat paw oedema induced by carrageenin. Compounds 6a, c, f and g (i.v.) significantly inhibited the rat paw oedema induced by carrageenin depending upon the dose employed. The compounds were also evaluated for their in vitro antimicrobial activity. Some compounds were found to have significant activity against Gram positive and Gram negative microorganisms.

Inhibition of eosinophil chemotaxis by chronic blockade of nitric oxide biosynthesis.

The effect of chronic N omega-nitro-L-arginine methyl ester (L-NAME) treatment on the in vivo eosinophil migration induced by bradykinin, platelet-activating factor (PAF), lipopolysaccharide and carrageenin has been investigated in the rat using the pleurisy model. The in vitro (microchemotaxis chamber) eosinophil migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP), PAF and zymosan-activated serum was also evaluated in the rat. The eosinophils were obtained from the peritoneal cavity of male Wistar rats and isolated on a discontinuous metrizamide gradient. Chronic inhibition of nitric oxide biosynthesis was achieved by adding L-NAME to the drinking water to give an intake of approximately 75 mumol/rat/day for 4 weeks. Rats treated chronically with L-NAME developed a significant level of hypertension (163 +/- 4.8 mmHg; P < 0.01) compared with animals which received either the same dose of the inactive enantiomer D-NAME (124 +/- 3.2 mmHg) or tap water alone (119 +/- 1.6 mmHg). The intrapleural injection of bradykinin (50 micrograms), PAF (1 microgram), lipopolysaccharide (0.25 microgram) and carrageenin (125 micrograms) into untreated rats in vivo induced a significant level of eosinophil migration by 24 h post-injection. This migration was markedly reduced in L-NAME-treated rats. Eosinophils obtained from untreated rats showed a significant level of migration in vitro in response to fMLP (5 X 10(-8) M), PAF (10(-8) M) and zymosan-activated serum (27 microliters). In contrast, the migration induced by these chemotactic agents was markedly reduced in cells isolated from animals treated chronically with L-NAME. L-Arginine (5.5 mM), but not D-arginine (5.5 mM), restored the ability of eosinophils from L-NAME-treated animals to migrate in response to fMLP. Our results indicate that nitric oxide plays a major role in the in vivo and ex vivo migration of eosinophils.

Effect of chronic nitric oxide synthesis inhibition on the inflammatory responses induced by carrageenin in rats.

The effect of chronic inhibition of nitric oxide (NO) biosynthesis has been investigated in two models of acute inflammation induced by carrageenin, i.e., paw oedema and pleurisy. Chronic inhibition of NO biosynthesis was achieved by including N omega-nitro-L-arginine methyl ester (L-NAME) in the drinking water to give a dose of approximately 75 mumol/rat/day for 2 and 4 weeks. Control animals received either tap water alone or the inactive enantiomer D-NAME. Since chronic NO inhibition increases blood pressure, rats made hypertensive (2 kidney-1 clip model; 2K-1C) were used to evaluate the effect of hypertension on the carrageenin-induced paw oedema. In a separate set of experiments, L-NAME-treated animals concomitantly received captopril (140 mumol/rat/day) to prevent hypertension. Animals chronically treated with L-NAME (but not D-NAME) for 2 and 4 weeks developed hypertension to the same extent as 2K-1C rats. Carrageenin-induced paw oedema was significantly reduced in animals chronically treated with L-NAME, but not with D-NAME or in 2K-1C rats. Subplantar injection of iloprost completely reversed the inhibition of paw oedema caused by L-NAME. Captopril (140 mumol/rat/day) significantly lowered the high blood pressure levels induced by L-NAME but did not significantly affect the inhibition of paw oedema caused by L-NAME. No changes in vascular permeability, as assessed by Evans blue extravasation, were observed in L-NAME-treated animals. The chronic treatment with L-NAME for 2 and 4 weeks did not inhibit carrageenin-induced leucocyte migration and fluid exudation into the pleural cavity. Although carrageenin-induced paw oedema is reduced in L-NAME-treated rats, this response reflects a decrease in local blood flow rather than an effect on vascular permeability.

Action of colchicine on hepatic schistosomal granuloma.

Amorphous material and altered collagen fragments within dilated secretory vesicles and cisternae of fibroblast cytoplasm were the main ultrastructural changes seen in hepatic periovular granulomas formed in mice infected with Schistosoma mansoni and treated with colchicine. Despite promoting ultrastructural changes in the fibroblasts found in hepatic periovular granulomas, colchicine administration to infected mice did not significantly change the light microscopic appearance of the hepatic schistosomal lesions, did not diminish the amount of total hepatic collagen, and did not change the collagen isotypes in the granulomas, as observed after a comparative study with non-colchicine treated infected control mice. When administered to mice two weeks after curative treatment of schistosomiasis with praziquantel, colchicine did not seem to increase extracellular collagen degradation or to induce a more rapid resorption of hepatic periovular granulomas, although still promoting ultrastructural alterations in fibroblasts.

Morphology and collagen isotypes of carrageenin granuloma.

1. Injection of carrageenin into the liver of rats provoked a focal necrotic-hemorrhagic lesion that evolved through acute inflammation, accumulation of macrophages and fibroblasts and the formation of a relatively large amount of fibrous tissue that underwent resorption. The entire lesion disappeared within 15-18 days of the beginning of inoculation. 2. Ultrastructural analysis revealed that carrageenin granules were taken up by macrophages, fibroblasts and myofibroblasts and that signs of formation and degradation of collagen were constant features, the former predominating early and the latter being evident toward the second half of the evolution of the lesion. 3. The presence of fibronectin was prominent during the first days and Type I and Type III collagens were present in the extracellular matrix soon after induction of the carrageenin lesion. Both collagen isotypes subsequently underwent progressive and simultaneous resorption. 4. The rapid formation and degradation of both collagen isotypes during the evolution of carrageenin granuloma indicates that collagen stability is not fundamentally dependent on genetic isotype.

Morphology and collagen isotypes of carrageenin granuloma

1. Injection of carrageenin into the liver of rats provoked a focal necrotic-hemorrhagic lesion that evolved through acute inflammation, accumulation of macrophages and fibroblasts and the formation of a relatively large amount of fibrous tissue that underwent resorption. The entire lesion disappeared within15-18 days of the beginning of incolulation. 2. Ultrastructural analysis revealed that carrageenin granules were taken up by macrophages, fibroblasts and myofibroblasts and that signs of formation and degradation of collagen were constant features, the former predominating early and the latter being evident to ward the second half of the evolution of the lesion. 3. The presence of fibronection was prominent during the first days and Type I and type III collagens were present in the extracellular matrix soon after induction of the carrageenin lesion. Both collagen isotypes subsequently underwent progressive and simultaneous resorption. 4. The rapid formation and degradation of both collagen isotypes during the evolution of carrageenin granuloma indicates that collagen stability is not fundamentally dependent on genetic isotype

Differences in hepatic pathology resulting from bile duct obstruction in young and old rats.

1. Young and adult rats subjected to complete bile duct ligation from 4 to 40 days revealed different liver histopathologies at the end of the experimental period. 2. In young rats, ductal and ductular proliferation resulted in septal fibrosis which, originating from the portal spaces, tended to delimit areas of nodular parenchymal transformation (secondary biliary cirrhosis). In adult rats, proliferating ductal and ductular structures diffusely invaded the hepatic parenchyma, dissociating the liver cell plates in a pattern similar to that of a malignant neoplastic growth. 3. The different result of the lesions in young and old rats suggests that an age-related factor may be involved in the pathogenesis of lesions resulting from biliary obstruction.

The importance of collateral portal veins for resistance to schistosomiasis in mice.

Mice with portal hypertension and collateral circulation caused by partial portal vein ligation yielded fewer worms than intact or sham-operated controls when infected with 50 Schistosoma mansoni cercariae for 8 weeks. The collateral circulation probably diverted arriving immature worms back to the general circulation where they died as the result of being out of their natural habitat rather than from immune killing. The present data strongly support the concept that a leaky portal system is the main factor in resistance to reinfection in murine schistosomiasis.