Biomedical subjects
Publications and source records attributed to I Arai.
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Anti-inflammatory, analgesic and anti-pyretic activities of orally administered TA were investigated in experimental animals. Against acetic acid-induced vascular permeability in mice, carrageenin-induced hind paw edema in rats and ultra-violet ray-induced erythema in guinea pigs, TA produced a dose related inhibition at doses of 40-160 mg/kg, 10-40 mg/kg and 10-40 mg/kg, respectively. TA produced no inhibition against histamine-induced vascular permeability even at a dose of 200 mg/kg in rats. Cotton pellet-induced granuloma and adjuvant-induced arthritis in rats were significantly inhibited by repeated administration of TA at a dose of 50 mg/kg/day for 6 days and 25 mg/kg/day for 6 days, respectively. TA showed a dose related analgesic effect at a dose of 50-200 mg/kg in acetic acid writhing, Randall-Selitto and adjuvant arthritic pain methods. A high dose of TA was needed to produce an analgesic effect in the pressure method using mice. TA produced an anti-pyretic effect against the pyrexia induced by yeast in rats. On the other hand, TA showed no effect against normal body temperature in rats. These results suggest that anti-inflammatory, analgesic and anti-pyretic activities of TA are generally a little weaker than those of ibuprofen, and the mode of action of TA is similar to that of a typical acidic non-steroidal anti-inflammatory drug such as ibuprofen, indomethacin or phenylbutazone. The ulcerogenic activity of TA was about 2 and 4 times weaker than that of ibuprofen in rats and mice, respectively. TA showed a protective effect against gastric necrosis induced by HCl.(ABSTRACT TRUNCATED AT 250 WORDS)
TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11-methylenedioxy-6-dibenzo[a,c]cyclooctenol) is one of the lignan compounds isolated from Schisandra fruits. 1) Effect of TJN-101 on liver fibrosis was investigated in rats which were injected with CCl4 (1 ml/kg) subcutaneously twice a week for 12 weeks. TJN-101 was given orally at the dose of 10 or 30 mg/kg/day for 6 or 3 weeks beginning on the 6th or 9th week after the start of CCl4-intoxication, respectively. The elevations of serum transaminase activities and the increase of liver 4-hydroxyproline content were observed depending on the period of CCl4-intoxication. These changes were marked on the 9th and 12th weeks after. In the histopathological study, the degenerative fatty change on the 6th week after and the formation of pseudolobule caused by fibrosis proliferation on the 9th or 12th week after were mainly observed. When rats were treated with TJN-101, the abnormalities in biochemical parameters and the fibrosis proliferation caused by CCl4-intoxication were improved. 2) Chronic liver injury was induced by the treatment with CCl4 (1 ml/kg) subcutaneously twice a week for 10 weeks to investigate the effect of TJN-101 on liver regeneration after partial hepatectomy. TJN-101, which was given orally at the dose of 10, 30 or 100 mg/kg/day for 6 days from the 1st day after partial hepatectomy, dose-dependently increased the liver regeneration rate and improved the serum BSP retention rate. These results suggest that TJN-101 suppresses the fibrosis proliferation and accelerates both the liver regeneration and the recovery of liver function after partial hepatectomy in chronic liver injury.
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Gastric ulcerations induced in rats by a combination of indomethacin and cold-stress (5 +/- 1 degrees C) for 6 hr were more severe than those induced by indomethacin or cold-stress alone. The acidity of gastric juice was increased in rats treated with indomethacin plus cold-stressed. Histamine H2 receptor antagonists, (H+-K+) ATPase inhibitors and prostaglandins inhibited gastric ulcer formation in indomethacin plus cold-stress treated rats, whereas anticholinergics aggravated the ulceration. The indomethacin plus cold-stress induced acid secretion was inhibited by cimetidine and omeprazole in pylorus-ligated rats. Atropine had less effect on the increase in acidity than cimetidine and omeprazole. These findings indicate that the ulcer formation in indomethacin plus cold-stress treated rats is related the increased in acidity of gastric juice. This gastric ulcer model may be useful for evaluating antiulcer agents.
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The effects of restraint and water-immersion stress (RWIS) on the cardiovascular system (including blood pressure, heart rate, blood flow in the gastric region, and blood flow in the common carotid artery and descending aorta) and body temperature were studied in rats. The blood pressure of RWIS rats did not differ from that of restraint stress (RS) rats. The heart rate, blood flow in the gastric region, common carotid artery and descending aorta as well as body temperature were significantly decreased by RWIS, but not by RS. The decrease in heart rate in RWIS rats was not influenced by pretreatment with atropine, hexamethonium or vagotomy. The reduction of gastric regional blood flow was not influenced by pretreatment with atropine and phenoxybenzamine. The changes in these three parameters were closely correlated in all the RWIS rats tested. These results suggest that the decrease in gastric regional blood flow is due to a lowering of the body temperature via decreasing cardiac output.
Effects of oral administration of gomisin A, one of the components isolated from Schizandra fruits, on liver injuries induced by CCl4, d-galactosamine and dl-ethionine and on liver microsomal drug-metabolizing enzyme activities were investigated. Gomisin A suppressed the increase of serum transaminase activities and the appearances of histological changes such as degeneration and necrosis of hepatocyte, inflammatory cell infiltration and fatty deposition in each type of liver injury. The repeated administration of gomisin A (30 or 100 mg/kg, p.o., daily for 4 days) induced an apparent increase of liver weight in liver-injured and normal rats. Gomisin A decreased serum triglyceride and lipid contents of the liver in biochemical studies. Increases of microsomal cytochrome b5 and P-450, elevations of NADPH cytochrome C reductase, aminopyrine N-demethylase and 7-ethoxycoumarin O-deethylase activities and decrease of 3,4-benzo(a)pyrene hydroxylase activity per cytochrome P-450 were observed after the administration of gomisin A. In addition, gomisin A was found to enhance the incorporation of 14C-phenylalanine into liver protein and to shorten the hexobarbital-induced sleeping time. These changes caused by gomisin A were similar to those by phenobarbital. However, gomisin A is distinctly different from phenobarbital in the finding that phenobarbital lessened the survival ratio of CCl4-intoxicated mice, but gomisin A did not. Our observation suggest that gomisin A shows an antihepatotoxic action by oral application and also has hypolipidemic (mainly triglyceridemic) and liver protein synthesis-facilitating actions and that the enlargement of the liver seen with gomisin A is the adaptive hypertrophy which is due to the induction of drug-metabolizing enzymes.
Effects of TJN-101, one of the components isolated from Schizandra fruits, on liver regeneration after partial hepatectomy, and on regional hepatic blood flow and fine structure of the liver were investigated in normal rats. TJN-101, which was administered orally at the doses of 10, 30 and 100 mg/kg/day for 4 days after partial hepatectomy, increased the regeneration rate of the liver and improved the serum retention rate of BSP which had been dose-dependently decreased after the operation. Elevation of serum protein to control levels, elevation of serum LCAT activity, decrease in plasma insulin and increase in plasma glucagon were all dose-dependent responses to TJN-101. The mitotic index on the 5th day after the operation was hardly influenced by TJN-101. Regional hepatic blood flow was increased after intraduodenal administration of TJN-101 (30 and 100 mg/kg). Ultrastructural studies of liver tissue using the transmission electron microscope revealed that TJN-101 stimulated an increase in rough and smooth endoplasmic reticulum in the groups receiving 100 and 300 mg/kg/day. These results suggest that TJN-101 accelerates both the proliferation of hepatocytes and the recovery of liver function after partial hepatectomy and increases hepatic blood flow. It is also thought that the liver enlargement caused by repeated administration of TJN-101 is associated with the proliferation of endoplasmic reticulum.
The effect of water temperature during restraint and water-immersion stress (RWIS) on gastric regional blood flow, acid secretion and ulcer formation were compared to those of restraint stress (RS) alone in rats. RS had no effect on the gastric regional blood flow. In contrast, the gastric regional blood flow was significantly decreased by RWIS. A water temperature dependent reduction of gastric regional blood flow induced by RWIS was observed between 20 degrees C and 30 degrees C. The decrease in gastric regional blood flow for RWIS rats was related to a lowering of the body temperature, which almost coincided with the temperature of water for the immersion. The gastric acid output was not influenced by RS. However, RWIS significantly increased the gastric acid output. The temperature of water in order of increasing acid output induced by RWIS was 25 degrees C greater than 30 degrees C greater than 20 degrees C. Little ulcer formation was found in RS rats, while exposure to RWIS caused marked ulceration. The temperature of water in order of severity of ulceration by RWIS was 25 degrees C greater than 20 degrees C greater than 30 degrees C. The severity of ulceration was not related to the decrease in gastric regional blood flow or increase of acid output, but was correlated to the ratio of the gastric blood flow/the acid output. These findings suggest that the decrease of gastric regional blood flow is in good agreement with the fall of body temperature, and the combined effects of the gastric blood flow and the acid secretion are involved in the ulceration caused by RWIS.
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Sofalcone prevented the formation of lesions by 50% ethanol and aspirin dose dependently, prevented the decrease in the gastric mucosal macromolecular glycoprotein content caused by these treatments, and prevented the decrease in the incorporation of 3H-glucosamine caused by ethanol and aspirin into the macromolecular glycoprotein. 35S-Sulfate incorporation, which was slightly decreased, by the administration of ethanol and aspirin, was significantly increased, and the specific activity of sulfated macromolecular glycoprotein synthesis which was not changed by ethanol or aspirin was increased by the administration of sofalcone prior to these treatments. These results suggest that the maintenance of the mucosal macromolecular glycoprotein content is involved in the protective effects of sofalcone against the formation of acute gastric lesions induced by ethanol and aspirin.
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The effects of wuweizisu C, a lignan component of schizandra fruits, on liver injuries induced by carbon tetrachloride (CCl4), d-galactosamine and dl-ethionine were investigated by means of serum-biochemical and histopathological examinations in rats. Pretreatment or combined administration of wuweizisu C dose-dependently reduced the elevation of serum transaminase activity and histological changes such as fatty degeneration, cell necrosis, inflammatory cell infiltration, etc., which were caused by the single administration of 1 ml/kg, p.o., or the repeated administration of 0.2 ml/kg, s.c., daily for 4 days of CCl4, respectively. The effects of wuweizisu C on the liver injuries induced by a low dose (200 mg/kg, i.p.) and a high dose (400 mg/kg, i.p.) of d-galactosamine were compared with those of uridine. Wuweizisu C significantly lowered the rise of serum transaminase activity after the administration of a low dose of d-galactosamine in the serum-biochemical analysis. A tendency was also shown to inhibit cell necrosis and inflammatory cell infiltration caused by both doses of d-galactosamine in the histopathological examination. On the other hand, uridine markedly repaired the serum-biochemical and histopathological changes after the administrations of both doses of d-galactosamine. Also wuweizisu C cured the liver injury by the repeated administration of 150 mg/kg, i.p., daily for 4 days of d-galactosamine. After the repeated administration of 250 mg/kg, s.c., daily for 4 days of ethionine, liver cell atrophy, diffuse fatty degeneration and decrease of serum triglyceride were observed, but not cell necrosis. Wuweizisu C dose-dependently inhibited fatty degeneration and decrease of serum triglyceride. These findings suggest that wuweizisu C can be protective and/or therapeutic on hepatocellular phenomena such as cell necrosis, fatty degeneration, inflammatory cell infiltration, etc., in human hepatitis.
Effects of several non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin (ASA), indomethacin (IM), flurbiprofen (FP), ibuprofen (IP), phenylbutazone (PBZ) and flufenamic acid (FA) were studied on the gastric ulceration and gastric acid secretion induced by restraint and water-immersion stress (RWIS) or various secretagogues in rats. These drugs significantly increased ulcer formation. IM (1, 3 and 10 mg/kg, s.c.) reduced gastric mucosal prostaglandin (PG) content dose-dependently. There was an appreciable correlation between this decrease in the PG content of gastric tissue and associated ulceration. The gastric acid secretion induced by the peripheral secretagogues, methacholine, gastrin and histamine, was not significantly influenced by IM pretreatment. In contrast, the gastric acid secretion induced by the vagal mediated secretagogues, insulin, 2-deoxy-D-glucose (2-D-G) and RWIS, was markedly increased by IM pretreatment. These effects were not observed in vagotomized rats. By intracerebroventricular (i.c.v.) injection of IM, no influence was observed on the gastric acid secretion and ulcer formation induced by 2-D-G or RWIS. These results suggest that acidic NSAIDs potentiate the gastric acid output induced by stimulation of vagus nerve activity, and prostaglandins (PGs) may influence gastric acid output by regulating vagus nerve activity.