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PubMed2003

Effects of ginseng saponin administered intraperitoneally on the hypothalamo-pituitary-adrenal axis in mice.

Intraperitoneal injection of ginseng total saponin (GTS; 5 and 20 mg/kg) raised plasma corticosterone levels in mice. However, interestingly, pretreatment of animals with the same doses of GTS (5 and 20 mg/kg) significantly attenuated the immobilization stress-induced increase in plasma corticosterone levels. Of the ginsenosides Rb(1), Rb(2), Rc, Rd, Re, Rf, Rg(1), 20(S)-Rg(3), and 20(R)-Rg(3) injected intraperitoneally at doses of 0.1-2 mg/kg, Rc (2 mg/kg) significantly inhibited the immobilization stress-induced increase in plasma corticosterone levels. GTS and Rc administered intraperitoneally did not affect the immobilization stress-induced elevation of plasma adrenocorticotropic hormone (ACTH) level. Pretreatment with GTS and Rc significantly attenuated the increase in plasma corticosterone levels induced by intraperitoneal injection of ACTH (30 microg/kg). These results suggest that GTS and Rc inhibit the immobilization stress-induced increase in plasma corticosterone levels by blocking ACTH action in the adrenal gland. Ginseng may be proposed to be useful for treatment of stress related disorders.

Adrenocorticotropic Hormone↗
PubMed1981

Studies on the increased potassium concentration of plasma produced by a hypertonic solution of low potent substances intraperitoneally administered to rats.

Intracranial hemorrhage was induced in rats by low potent substances, glucose, NaCl and Na2SO4, intraperitoneally injected in enormous amounts, that is, 2800 mOsmol/L (J. Toxicol. Sci. 5, 290, 1980). The present study was undertaken to examine a mechanism of the above mentioned phenomenon in detail from the aspects of the disturbance of water-electrolyte balances and the change in blood osmolality. After administration of hypertonic solutions, blood and abdominal fluid were obtained at intervals of 5 to 15 min and at death. Hypertonic solutions injected intraperitoneally induced rapid exchange in water and solute across the peritoneum, thus causing an increase in abdominal fluid volume and plasma osmolality. Most interesting was the fact that a marked potassemia was produced and that the value of plasma potassium reached 10 mEq/L at death in all of groups of intraperitoneally injected rats. Thus, it is clear that the intracranial hemorrhage is accompanied by an increase in the plasma concentration of potassium which does not always run parallel with an increase in sodium concentration and osmotic pressure in rat plasma.

Animals↗
PubMed1990

Roles of bile and bacteria in biliary peritonitis.

Bile is known to have an adverse effect in peritonitis but the mechanism(s) and site of action of bile are unknown, as are the relative roles of bile and bacteria. The present study was designed to answer some of these questions. Experiments in which rats were injected intraperitoneally and intravenously with bile, Escherichia coli or saline showed that bile had no systemic toxicity and that it increased the mortality rate only when introduced into the peritoneal cavity together with bacteria. Measurements of peritoneal fluid volumes and blood pressure did not confirm the theory that the increased mortality rate was a consequence of loss of plasma volume into the peritoneal cavity. The number of intraperitoneal bacteria decreased continuously in animals receiving intraperitoneal E. coli alone. When bile was added by intraperitoneal injection, the number of intraperitoneal bacteria started to rise at 2 h and then increased steadily with a consequent bacteraemia at 10 h. The number of bacteria per peritoneal phagocyte was significantly lower after intraperitoneal injection of E. coli and bile, when compared with injection of E. coli alone. It is concluded that bile exerts its detrimental effect within the peritoneal cavity in the presence of bacteria. Bile impairs local host defence in a way that remains unknown and may be related to the detergent-lytic effects of bile salts.

Animals↗
PubMed1997

Kinetics of bupivacaine after levcromakalim treatment in mice.

Previous workers have reported that 0.01 mg kg-1 of levcromakalim injected intraperitoneally did not modify bupivacaine-induced neurotoxicity but increased the duration of action of bupivacaine. This study was designed to document possible changes in the pharmacokinetic behaviour of bupivacaine and its main metabolite, N-desbutylbupivacaine in mice after a single 0.01 mg kg-1 intraperitoneal injection of levcromakalim. The kinetic parameters of bupivacaine were determined after a single 20 mg kg-1 intraperitoneal injection of bupivacaine in controls and in levcromakalim-treated mice. It was found that levcromakalim did not change any kinetic parameters of bupivacaine or of its main metabolite, N-desbutylbupivacaine. The previously reported findings of the influence of the low dose (0.01 mg kg-1) of levcromakalim on bupivacaine-induced toxicity agree well with the lack of influence of 0.01 mg kg-1 of levcromakalim on bupivacaine and N-desbutylbupivacaine pharmacokinetics, although the reported increase in the duration of action of bupivacaine after levcromakalim treatment can hardly be explained by the pharmacokinetics of bupivacaine when associated with levcromakalim. We suggest that levcromakalim might interfere directly with ion-channel block caused by bupivacaine by altering conduction properties or indirectly by enhancing bupivacaine-induced voltage and time-dependent sodium-channel block.

Anesthetics, Local↗
PubMed1989

[Studies on chemical protectors against radiation. XXVII. Survival effects of methanol extracts of various Chinese traditional medicines on radiation injury].

The survival effect of mice irradiated with a lethal dose of X-ray was studied by use of 60 kinds of Chinese traditional medicines. Methanol extracts of these medicines were prepared, and then each extract injected intraperitoneally into male mice before or after whole-body irradiation. As a result of these studies, the survival effects with Ogi-kentyu-to, Simotu-to, Sessyo-in, Zokumei-to and Boi-ogi-to were observed by intraperitoneal injection before irradiation. Of these effective methanol extracts, only Zokumei-to was shown to have a significant survival effect by intraperitoneal injection after irradiation.

Animals↗
PubMed1991

Satiating effect of bombesin is mediated by receptors perfused by celiac artery.

The abdominal site or sites for the satiety action of exogenous, peripherally administered bombesin (BN) were investigated. By use of a chronic arterial catheterization technique, the effects of 1, 2, and 4 micrograms/kg BN on liquid food intake of nondeprived male rats were assessed. Comparisons were made between the effects of these doses infused into the celiac or superior mesenteric arteries or injected intraperitoneally. The satiating potency of exogenous BN was significantly enhanced by direct administration into the celiac artery, which directly perfuses the stomach, pancreas, liver, spleen, and proximal duodenum. By this route, 4 micrograms/kg BN produced greater than 60% suppression of 15-min food intake. By contrast, BN infused into the superior mesenteric artery was no more effective than intraperitoneal injection. Celiac infusion of 1 micrograms/kg BN produced a suppression (30%) of intake that was equivalent to, or exceeded, that obtained after intraperitoneal injection or superior mesenteric infusion of 4 micrograms/kg. These results strongly support an upper abdominal, and possibly gastric, site for the satiety action of peripherally administered BN.

Animals↗
PubMed1990

[Studies on chemical protectors against radiation. XXIX. Protective effects of methanol extracts of various Chinese traditional medicines on skin injury induced by X-irradiation].

In order to investigate useful protective medicines for the relief of skin injury induced by irradiation, 60 methanol extracts of Chinese traditional medicines were used in the test of protective potency on skin injury. ICR male mice at 6 weeks of age were whole-body irradiated with 1100R by using a soft X-ray generator (30 kVp, 10 mA, 190 R/min). Each methanol extract of these medicines was injected intraperitoneally into mice before or after irradiation. The degrees of skin injury were determined by a score system of skin reaction within the observation period from 21st to 40th day after irradiation. Protective potency of each medicine on skin injury was calculated from the maximum mean scores of administrated group and un-administrated group. As a result of these studies, the protective potency was detected in Unsei-in, Kumibinro-to, Keisi-syakuyaku-chimo-to, Keigai-rengyo-to, Gosyuyu-to, Koso-san, Saiko-seikan-to, Syo-kankyo-to, Syo-saiko-to, Syoma-kakkon-to, Sen-kan-meimoku-to, Zokumei-to, Sokei-kakketu-to, Bokuryo-in, Mao-to and Rikkunsi-to by intraperitoneal injection before irradiation. Of these effective medicines, only Unsei-in and Mao-to are shown to have a significant protective effect by intraperitoneal injection after irradiation.

Animals↗
PubMed2003

[Relationship between learning ability and memory and free radical in hippocampus of old rats].

OBJECTIVE: To study the relationship between the amount of free radical in hippocampus and the learning ability and memory in old rats. METHODS: Morris water maze was used for 10 days to examine the learning scores, latency scores, and the loci of movement in the maze among 46 old rats (aged 20 months), 36 young rats (aged 6 months), and 34 adult rats (aged 12 months). Salicylate was injected intraperitoneally and hippocampus dialysis was performed. Chromatography was used to measure the basic values of 2,3DHBA and 2,5DHBA in dialysis fluid chemiluminometry was used to measure the superoxide dismutrase (SOD) in the sample. The rats were killed and their brains were taken out. Histological examination was conducted to calculate the number of neurons in CA1, CA4, and PM regions in hippocampus. RESULTS: The learning scores on the first, fifth, and tenth days were 36.5 +/- 5.9 sec, 38.6 +/- 5.9 sec, and 39.4 +/- 6.9 sec (P > 0.05) in the old rats; 60.2 +/- 5.4 sec, 156.8 +/- 5.8 sec, and 165.1 +/- 6.8 sec in the young rats; and 61.7 +/- 5.8 sec, 152.3 +/- 6.9 sec, and 168.7 +/- 6.5 sec in adult rats. The learning scores at any time point of old rats were significantly lower than those of the young and adults rats (all P < 0.01). The latency scores of the first, fifth, and tenth days were 25.7 +/- 1.2 sec, 27.5 +/- 1.9 sec, and 27.7 +/- 1.9 sec in the old rats without significant difference between any two of these values (P > 0.05), however, the 3 latency scores of the old rats were all significantly larger than those of the young and adult rats (21.8 +/- 1.7 sec, 5.9 +/- 1.0 sec, and 3.6 +/- 0.6 sec, and 21.8 +/- 1.6 sec, 5.0 +/- 0.9 sec, and 4.8 +/- 0.7 sec respectively, all P < 0.01). The basic value of 2,3DHBA after intraperitoneal injection of salicylate was 20.7 +/- 0.3 pmol/ml in the old rats, 5 times that of the young rats and 6 times that of the adult rats (P < 0.01). The basic value of 2,5DHBA after intraperitoneal injection of salicylate was 60.12 pmol/ml in the old rats, 6 times that of the young rats and 5.8 times that of the adult rats (P < 0.01). The SOD activity was 410 U x g(-1) x min(-1) +/- 50 U x g(-1) x min(-1), significantly lower than those in the young and adult rats (880 U x g(-1) x min(-1) +/- 62 U x g(-1) x min(-1) and 860 U x g(-1) x min(-1) +/- 60 U x g(-1) x min(-1) (both P < 0.01). The values of neuron density in CA1, CA4, and PM regions of the old rats were all significantly lower than those of the young and adult rats (all P < 0.01). CONCLUSION: The decrease of learning ability in old rat is positively correlated with the increase of free radicals and loss of neurons in hippocampus.

Aging↗
PubMed1996

Middle-sized molecule fractions isolated from uremic ultrafiltrate and normal urine inhibit ingestive behavior in the rat.

Uremic patients with suppressed food intake may regain appetite soon after starting dialysis, presumably because of the removal of one or more toxic factors that suppress appetite. To investigate this matter, this study used a new experimental model in free-moving, unstressed male Wistar rats (300 to 350 g) with feeding catheters channeled from the top of the skull to the oral cavity. When the rats recovered from surgery, they were tested under standardized conditions by being given an intraoral infusion (1 mL/min) of a 1 M sucrose solution or a 97 g/L protein solution or a mixed solution of carbohydrate, protein, and fat (Fortimel (Nutricia Nordica AB, Stockholm, Sweden)) while the time (volume) of ingestion was recorded. Solutions to be tested for their ability to inhibit ingestion were injected intraperitoneally (lp) and the intraoral infusion was started 20 min later. Plasma ultrafiltrate was collected from end-stage renal failure patients by isolated ultrafiltration at the beginning of their first hemodialysis and pooled. Ultrafiltrate was also obtained by filtering pooled plasma from healthy volunteers in vitro, using the same type of dialyzer and cellulose acetate membranes as those used in the uremic patients. Morning urine samples from healthy volunteers were pooled and subjected to the same in vitro filtration procedure as the normal plasma. Intraperitoneal injection of 20 mL normal ultrafiltrate had no effect on sucrose ingestion, whereas injection of 20 mL uremic ultrafiltrate reduced the ingestion of sucrose solution by 23% and the ingestion of Fortimel by 17%. Ten mL of ultrafiltrate from normal urine reduced the sucrose intake by 42%. The pooled ultrafiltrates from normal and uremic plasma and normal urine were subjected to molecular filtrations using a series of membranes with known cut-off points. The filtrations yielded four concentrated fractions with molecular weight ranges of 0.1 to 0.5 kilodaltons (kd), 0.5 to 1 kd, 1 to 5 kd, and 5 to 10 kd, respectively; the plasma fractions were concentrated a factor of about 25:1 and the urine fractions by about 15:1. After an ip injection of 2 mL of each concentrated plasma fraction, only the 1 to 5 kd fraction from the uremic ultrafiltrate inhibited sucrose intake, whereas the corresponding fraction from the normal ultrafiltrate had no effect. After injection of 1, 3, and 5 mL of the concentrated fractions of uremic ultrafiltrate, a dose-dependent inhibition of sucrose intake was achieved with the 1 to 5 kd fraction and, to a lesser extent, with the 5 to 10 kd fraction. Intraperitoneal injection of 0.5, 1.0, and 2 mL of the concentrated 1 to 5 kd fraction, but not of the other fractions from normal urine, also resulted in a dose-dependent inhibition of sucrose intake. The 1 to 5 kd fractions from the uremic ultrafiltrate and the normal urine ultrafiltrate also inhibited protein intake in a dose-dependent manner. These results suggest that one or more toxic compounds in the middle-molecule weight range, which are normally excreted in the urine, accumulate in uremia and suppress food intake.

Animals↗
PubMed1980

Failure to stimulate a local immune response in the mammary gland of the sow using intraperitoneal "priming".

An experiment was carried out to determine whether a local immune response could be produced in the mammary gland of sows by "priming" the animals with an intraperitoneal injection of antigen without adjuvant. Adjuvant was not used in the immunization regimen because it had been shown to induce acute peritonitis and multiple abscess formation when injected intraperitoneally in pigs. Four pregnant sows were "primed" by intraperitoneal injection of ferritin; a second dose of the antigen was given two weeks later into the lumen of the jejunum. Another group of pregnant sows was given two intra-muscular injections of ferritin two weeks apart and a third group of sows served as non-immunized controls. Antibody titres and concentrations of IgG, IgA and IgM in colostral and milk whey suggested that a local immune response had not been stimulated in the mammary glands of these sows. Mammary tissue was examined for the presence of immunoglobulin-containing and specific antibody-containing plasma cells. Results of these studies confirmed that intraperitoneal/intrajejunal injection of ferritin without adjuvant was not successful in inducing a local immune response in the mammary gland.

Animals↗
PubMed1991

Time-gated fluorescence spectroscopy of porphyrin derivatives and aluminium phthalocyanine incorporated in vivo in a murine ascitic tumour model.

The effect of systemic administration on drug uptake at cellular level was evaluated using time-gated fluorescence spectroscopy performed on a murine ascitic tumour model. Mice bearing L1210 leukaemia were injected intraperitoneally or intravenously with 25 mg per kg body weight hematoporphyrin derivative (HpD), 12.5 mg per kg body weight photofrin II (PII), 25 or 5 mg per kg body weight disulphonated aluminium phthalocyanine (AlS2Pc). Every 2 h and for up to 22 or 30 h, mice were sacrificed, leukaemic cells extracted from the peritoneum, washed, and resuspended in buffer for fluorescence measurements. HpD and PII emission spectra were almost identical 12 h after intraperitoneal injection with main peaks at 630 nm and no appreciable changes afterwards. In the first 12 h, the PII fluorescence spectrum was constant, while in the case of HpD a shoulder at 615 nm was detectable. Similar fluorescence behaviour was observed after intravenous administration of porphyrin derivatives. These results seem to confirm that the tumour localizing fraction is the part actually retained by the cells. The AlS2Pc spectrum peaked at 685 nm and did not change in any of our experiments. AlS2Pc is incorporated more rapidly with respect to porphyrins, as was clearly observed in the case of intravenous administration, where the AlS2Pc fluorescence was readily detectable after 2 h, whereas the PII emission became apparent only after 4-6 h.

Aluminum↗
PubMed1975

The lethal effect of mebendazole on secondary Echinococcus granulosus, cysticerci of Taenia pisiformis and tetrathyridia of Mesocestoides corti.

Oral administration of mebendazole at a rate of 1 g/kg feed (approximately 50 mg/kg body weight/day) for 14 days killed mature and immature cysticerci of Taenia pisiformis in rabbits, and multiplying tetrathyridia of Mesocestoides corti in mice. Progressive degrees of parasite damage caused by mebendazole treatment could be assessed by histological examination of calcereous corpuscles. A single subcutaneous injection of 10 percent mebendazole in carrier, at a rate of 100 mg/kg body weight, resulted in the death of all M. corti tetrathyridia in mice within 4 weeks, but the drug in saline was slowly mobilized and was relatively ineffective. Neither subcutaneous injections of mebendazole in saline or in carrier could kill cysticerci of T. pisiformis within 5 weeks, but the drug in carrier was effective after several months. Mebendazole in saline was effective when injected intraperitoneally, but adhesions often resulted from this route of administration. Echinococcus granulosus protoscoleces administered to mice by intraperitoneal injection were rapidly encapsulated by host lymphoid cells. The vesiculating protoscoleces were all contained within a fibrous capsule for more than 2 months after infection, but by 4 months almost all had grown free of the host reaction. Treatment of the encapsulated protoscoleces with mebendazole in feed for 14-21 days caused collapse of the outer cysts and death of the germinal membrane of all but the innermost protoscoleces. Six weeks later, however, cysts had regrown from surviving germinal tissue and a further treatment with mebendazole in feed for 14-21 days again did not destroy all germinal cells. Treatment of the 4-month-old scoleces with mebendazole in feed for 14 days caused all cysts to collapse and destroyed practically all E. granulosus germinal tissue. Three subcutaneous injections of mebendazole at fortnightly intervals, of drug in saline at 500 mg/kg body weight, or in carrier at 100 mg/dg body weight, were required in order apparently to kill all secondary cysts of E. granulosus. Host lymphoid cells were not able to traverse the laminated membrane of either untreated or collapsed cysts, and it has been shown that only a small amount of living germinative tissue is required to produce a new E. granulosus cyst. These factors could contribute to the relative ability of E. granulosus cysts to recover from mebendazole treatment, compared with cysticerci or tetrathyridia. The effectiveness of mebendazole thus seemed to depend on the formulation of the drug and its route of administration. Mebendazole is probably the first anthelmintic to have a lethal effect on larval cestodes. When applied orally there do not appear to be any adverse effects due to treatment.

Administration, Oral↗
PubMed1981

Bioassay of metals for carcinogenesis: whole animals.

Metals have been evaluated as potential carcinogens by administering pure elements or compounds by a large variety of routes. These include mixing the agent in the food, dissolving the test compound in the drinking water, or administering the material by gavage. The respiratory tract routes tested include inhalation, intratracheal instillation, the direct injection of particulates into the pleural cavity, or the implantation of hooks by surgical intervention. The parenteral routes used were intravenous injection, intraperitoneal injection, subcutaneous implantation, as well as intrafemoral and intramuscular injection. This latter route is the most commonly used. There are major objections to the subcutaneous implantations route, and data generated from these experiments are difficult to interpret for the foreign body reaction may give rise also to fibrosarcomas. This then is a nonspecific reaction. Exotic routes tested include intrarenal, intratesticular, and intracranial injections. The endpoints of the carcinogenic reactions are, in the main, sarcomas of certain types with fibrosarcomas predominating. Rhabdomyosarcomas are the next most frequent cancer found, and squamous cell carcinoma may account for less than 2% of the cancers reported. Much more research is necessary to clarify the nature of metal carcinogenesis. Dose-response information is almost nonexistent; the divided dose problem has not been studied adequately, and very little information is available on interspecies reactions. More work is needed to help interpret the mechanism of action.

Administration, Oral↗
PubMed1999

Evidence of splanchnic-brain signaling in inhibition of ingestive behavior by middle molecules.

Anorexia, nausea, and vomiting are common symptoms of uremic intoxication. Fractions in the middle molecule weight range, isolated from normal urine and uremic plasma ultrafiltrate, inhibit ingestive behavior in the rat. To investigate their site of action and specificity, male rats were injected intraperitoneally, intravenously, or intracerebroventricularly with concentrated fractions of uremic plasma ultrafiltrate or normal urine (molecular weight range: 1.0 to 5.0 kD) and tested for ingestive and sexual behavior. An intraperitoneal injection of 0.5 ml of urine fraction (10:1) or 2.0 ml of uremic plasma ultrafiltrate fraction (25:1) inhibited carbohydrate intake by 76.3 and 45.9%, respectively, but an intravenous injection had no effect. However, intravenous injection of higher doses inhibited carbohydrate ingestion. An intracerebroventricular injection of 5 or 10 microl of urine (20:1) middle molecule fraction inhibited carbohydrate intake by 13.4 and 41.6%, respectively. An injection of 5 or 10 microl of uremic plasma ultrafiltrate (125:1) middle molecule fraction inhibited carbohydrate intake by 22.6 and 49.5%, respectively. Injections of the corresponding fraction from normal plasma ultrafiltrate had no effect. Injection of urine or uremic plasma ultrafiltrate middle molecule fractions did not affect the display of sexual behavior. These results suggest that middle molecule fractions from uremic plasma ultrafiltrate or normal urine act in the splanchnic region and/or brain to inhibit food intake and that the effect is specific for ingestive behavior.

Animals↗
PubMed1991

Metabolic adaptation of renal carbohydrate metabolism. IV. The use of site-specific liver gluconeogenesis inhibitors to ascertain the role of renal gluconeogenesis.

The in vitro and in vivo effects of several different inhibitors of carbohydrate metabolism have been studied. The in vitro addition of 5-methoxyindole-2-carboxylic acid (MICA), pent-4-enoic acid, and quinolinic acid to the perfusion medium significantly inhibited liver gluconeogenesis in 48-hour-starved rats (100% inhibition when MICA and quinolinic acid were added at 0.8 and 2.4 mM, respectively). In vivo the level of inhibition varied greatly depending upon whether MICA was administered by intragastric tube or intraperitoneal injection. In all cases the inhibitory capacity of MICA on liver gluconeogenesis was significantly higher when injected intraperitoneally. On the other hand, the administration of MICA produced a significant, dose-dependent, increase in renal gluconeogenesis in both fed and 48-hour-starved rats, more so when the inhibitor was administered by intraperitoneal injection.

Animals↗
PubMed1975

Changes of certain pharmacological and biochemical indices in acute methylglyoxal poisoning.

Methylglyoxal in doses over 25 mg/kg injected intravenously in cats and rabbits produces distinct changes in the cardiovascular and respiratory systems, but has no effect on respiration or circulation when injected intraperitoneally even in doses up to 1 g/kg. The effect of MG on blood pressure depends on the species of the animal. The effects of MG are dose-related and dependent on the route of its administration. Biochemical studies showed a significant rise in serum activities of creatine kinase (EC 2-7-3-2), lactate dehydrogenase (EC 1-1-1-27) and aspartate aminotransferase (EC 2-6-1-1-) after intraperitoneal injection of MG in the dose of 200 mg/kg in rabbits and 500 mg/kg in rats. The observed changes probably indicate damage of muscle tissue by MG, presumably as a result of low content of one of the glyoxalases in the muscles of the experimental animals. Elevation of glucose levels by MG was probably an adrenergic effect. These biochemical changes can serve to evaluate toxicity of MG preparations, which exhibit variations probably owing to varying degree of polymerization.

Alanine Transaminase↗
PubMed2004

[Effect of melatonin on the expression of nuclear factor-kappa B and airway inflammation in asthmatic rats].

OBJECTIVE: Nuclear factor-kappa B (NF-kappaB) is a critical transcription factor governing the expression of many cytokines that are involved in the pathogenesis of inflammatory diseases, such as asthma and rheumatoid arthritis. Melatonin (MT), a relatively safe and potent antioxidant which has shown efficacy in several chronic inflammatory models, may inhibit the expression of NF-kappaB and therefore might have a therapeutic use in asthma. This study aimed at observing the effect of MT on the expression of NF-kappaB and airway inflammation in a rat model of bronchial asthma. METHODS: Twenty-four male Sprague-Dawley (SD) rats weighing 120 g to 170 g were randomly divided into three experimental groups (8 in each): (1) Asthmatic group: Rats were immunized on day 1 by intraperitoneal injection of 100 mg ovalbumin (OVA) in 1 ml of saline with 100 mg of alu minum hydroxide. From day 15 the animals were challenged with aerosolized OVA (1% in saline) for 20 minutes per day for 7 consecutive days. (2) MT group: OVA-sensitized rats were injected intraperitoneally with 10 mg/kg MT 30 minutes before each OVA challenge. (3) CONTROL GROUP: OVA for inhalation and MT for intraperitoneal injection was replaced with normal saline (NS). Airway responsiveness to aerosolized acetylcholine of 24 rats was detected six hours after the last challenge. Then the rats were lavaged and total and differentiated leukocytes counts in bronchoalveolar lavage fluid (BALF) were performed after staining with Wright-Giemsa staining. At the same time, levels of nitric oxide (NO) in BALF, inducible nitric oxide synthesis (iNOS) and constitute nitric oxide synthesis (cNOS) in the lung tissues were assessed with the use of nitrate reductase and chemical colorimetry, respectively. The expression of NF-kappaB in the lung tissues was observed by means of immunohistochemical staining. RESULTS: (1) After OVA challenge, there was a significant decrease in airway responsiveness, lymphocytes and eosinophils in BALF in MT group compared with asthmatic group (P < 0.01 respectively); (2) There was a significant decrease in amounts of NO(2)(-)/NO(3)(-) in the BALF and levels of iNOS in the lung tissues in MT group comparing with asthmatic group (P < 0.01 respectively); and the levels of iNOS in the lung tissues was correlated positively with NO(2)(-)/NO(3)(-) in the BALF (P < 0.01), but there were no significant differences in activity of cNOS in any of the groups analyzed. (3) There was a significant increase in expression of NF-kappaB in lung tissues in asthmatic group compared with the other groups (P < 0.01), and so was in MT group compared with control group (P < 0.05). CONCLUSIONS: MT could partially inhibit the expression of NF-kappaB and down-regulate the activity of iNOS in lung tissue, decrease the production of NO in BALF. These data suggest that the inhibitory effect of MT probably play a role in decreasing airway hyperresponsiveness and airway inflammation of asthmatic rats model.

Animals↗
PubMedDate not supplied

Effect of noradrenaline on the content, synthesis and catabolism of acetylcholine in the brain.

ACh synthesis and content in the cerebral cortex and brain stem as well as the activity of choline acetylase (AcCh) and acetylcholinesterase (AchE) in brain homogenates were determined after NA administration both in vivo and in in vitro. In in vivo experiments NA was injected intraperitoneally or into the lateral ventricle of the brain. Intraperitoneal injection of NA caused a significant fall of ACh content in the cerebral cortex. AchE activity was inhibited after intraventricular NA injection and in in vitro investigations, in which NA was added into the incubation medium. ACh synthesis and AcCh activity showed no abnormalities after NA administration in vivo and in vitro.

Acetylcholine↗