Acrocarpus fraxinifolius Wight and Arn. Bark; phenolics, toxicity studies, antioxidant and anti-inflammatory activities

The purpose of the survey was to determine acute & chronic toxicity; in vivo antioxidant and anti-inflammatory actions of the different extracts of A. fraxinifolius Wight and Arn bark; along with estimation of the phenolic, flavonoidal contents and investigation of phenolic metabolites that may attribute to the activities. LD50 of the total ethanol extract (TEE) was 7.1 g/kg b. wt, the radical scavenging activity of DPPH showed 60.31% inhibition, FRAP ability and ABTS+ activity showed 55.024 and 67.217 µmol Trolox/100 g dry weight, respectively. TEE followed by ethyl acetate extract (EAE) at 100 mg/kg b.w exhibited the highest in vivo antioxidant activity (94.51% and 91.08% potency, respectively) compared with Vit E (100%). The TEE & EAE exhibited the highest anti-inflammatory activity (3.81±0.08 & 3.79±.0.04) respectively in comparison with indomethacin 3.83±0.01 measured as edema diameter after 4 hours of extract administration. The total phenolic and total flavonoid contents in the total ethanol extract (TEE) estimated as gallic acid and catechin equivalents were 61.06± 0.08 µg eq GA/g, 40.33± 0.20 µg CE/g extract respectively. EAE revealed five phenolic acids and eight flavonoid compounds isolated for the first time from the plant

Effect of Trimebutine on hepatic injury caused by carbon tetrachloride in the rat

We investigated the effects of trimebutine, a peripheral opiate agonist, used in therapy of irritable bowel syndrome on the development of hepatic injury in rats treated with carbon tetrachloride. When administred s.c., at 30, 60 and 120 mg/kg, the drug increased the degree of hepatic damage caused by CCL[4] in a dose-dependent manner as reflected by serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP] and liver histopathology determined 14 days after drug administration. The effect was dose-dependant one, being most evident after administration of 60 and 120 mg/kg dose of the drug. Thus, compared with the CCl[4][control group, serum ALT increased by 28.9, 47.2%, AST by 16.2, 24.8% and ALP by 28.8, 47.2% after the administration of trimebutine at 60 and 120 mg/kg, respectively. When silymarin was combined with 120 mg/kg of trimebutine, the activities of ALT and AST were comparable with those seen after the administration of silymarin alone, suggesting a protective effect for silymarin against the increases in tranaminases by trimebutine. Histopathologic examination of the liver of rats treated with CCl[4] + trimebutine at a dose of 120 mg/kg showed massive inflammatory cellular infiltrate, fatty change and vacuolar degeneration. These changes were less marked in rats treated with CCl[4] + silymarin + 120 mg/kg trimebutine. It is concluded that the opiate agonist trimebutine aggrevates hepatocellular injury caused by CCl[4] in rats, which can be lessened by coadminisration of silymarin. We suggest monitoring of hepatic functions in patients on long term use of this drug, especially in those with already known hepatic dysfunction such as steatosis or HCV infected individuals. The administration of silymarin in patients on long-term use of trimebutine is advisable

experimental studies of the anti-inflammatory and gastric effects of ribavirin in rats

In the present study we examined effects of the broad-spectrum antiviral agent ribavirin on inflammation and gastric integrity in rats. Ribavirin 30120 mg/kg. i.p., administered 30 min beforehand, had no significant effect on carrageenan induced oedema, meanwhile a higher dose of 240 mg/kg significantly inhibited the formalin-induced paw oedema for 2 h. Injection of ribavirin in rats treated with indomethacin, rofecoxib or meloxican caused a further decrease in paw volume of carrageenan injected rats by 21.7, 23.6 and 71.2% at 4 h., respectively. It is suggested that ribavirin administered via systemic route possesses anti-inflammatory properties. Ribavirin 30-120 mg/kg, s.c, reduced the number and severity of gastric lesions caused by indomethacin [20 mg/kg, i.p.] in a dose-dependent manner. In urethane-anaesthetised rats, the drug inhibited gastric acid secretion induced by distention or distension plus histamine stimulation. The drug increases the anti-inflammatory action of NSAIDs, while reducing their gastric side effects

Investigation of the effect of unfractionated and low molecular weight heparins on inflammation and gastrointestinal mucosal injury in rats

The aim of the present work was to investigate the effect of unfractionated heparin [UFH; 1000-4000 IU/kg] in addition to three already marketed low molecular weight heparin [LMWH] preparations [nadroparin [1500-3000 anti-Xa IU/kg], tinzaparin [1500-3000 anti-Xa IU/kg], enoxaparin [300-600 anti-Xa IU/kg] on acute inflammation and on gastrointestinal mucosal integrity in rats. Acute inflammation was induced by intraplantar injection of carrageenan into rat hindpaw. Gastrointestinal mucosal injury was evoked by subcutaneous injection of indomethacin [20 mg/kg]. The results showed that: [1] Different heparin preparations given s.c., 30 mm prior to carrageenan injection exerted variable effects on the carrageenan oedema response. Oedema was not significantly changed after conventional UFH, but decreased after tinzaparin and nadroparin, the lower doses being more effective in reducing inflammation. Oedema was unchanged after enoxaparin at 600 IU/kg, but the lower dose of 300 IU/kg reduced oedema formation by 21.6% 1 h post-carrageenan.; [2] No significant change was noted in the number and severity of gastric mucosal lesions in rats treated with UFH. A significant decrease in number and severity of gastric mucosal lesions was noted in rats treated with the lower doses of either tinzaparin or enoxaparin compared with either the indomethacin control group or with the UFH [2000 IU/kg]-treated group. It is concluded that heparin preparations exert complex effects on acute [carrageenan-induced] inflammation and might have beneficial effects on gastric mucosal lesions caused by Indomethacin

Studies on the effect of the opioid receptor agonist "trimebutine" on inflammation, pain and gastric ulceration in rats

The effects of trimebutine, a peripheral opiate agonist, were investigated on the development of paw oedema by carrageenan, on visceral nociception caused by i.p. injection of acetic acid, on gastric mucosal injury induced by indomethacin and on gastric acid secretion in rats. I.p administration of trimebutine at 30, 60 or 120 mg/kg, at 30-min pretreatment, decreased paw oedema caused by carrageenan injection by 18.2-21.6%, 27.3%- 22.8% and 33.6%- 29.3%, respectively, with maximal inhibition being observed at 1-2 hr post-carrageenan. In addition, trimebutine in doses of 30, 60 or 120 mg/kg [i.p.] 30 mm after carrageenan challenge inhibited the paw oedema response by -21.2, -17%, 22.3, -21.2% and -33.1, -30% at 3 and 4 hr post-carrageenan, respectively. Trimebutine [60 mg/kg] co-administered with meloxicam [3.8 mg/kg], indomethacin [18 mg/kg] or dexamethasone [0.2 mg/kg] resulted in an additive effect. Abdominal writhes induced by i.p. injection of acetic acid were effectively inhibited by trimebutine. The drug enhanced the development of lesions by indomethacin in a dose-dependent manner. In anaesthetised rats, trimebutine caused dose-dependent inhibition of gastric acid secretion. Results indicate that trimebutine possesses anti-inflammatory properties in addition to its visceral analgesic effects. The drug likely exacerbates gastric mucosal lesions by non-steroidal anti inflammatory drugs and consequently their concurrent administration is not advisable

Comparison of the anti-inflammatory, analgesic and gastric effects of vinpocetine and piracetam in rats

The nootropic agents vinpocetine and piracetam are widely used in the treatment of memory and neurodegenerative disorders. The current study compared the effects of the two drugs in experimental models of inflammation and on the development of gastric mucosal damage evoked by indomethacin in rats. In paw oedema caused by subplantar injection of carrageenan, vinpocetine, given s.c., at doses of 0.45-1.8 mg/kg, produced only a slight decrease in paw volume. By contrast, piracetam administered s.c., at 75 mg/kg, significantly inhibited the oedema response, but at a higher dose 300 mg/kg produced a sustained dose-related increases in paw volume. In the hot-plate test of thermal pain, vinpocetine, but not piracetam, produced a dose-related reduction in nociceptive responses. Gastric mucosal lesions induced by s.c. indomethacin [20 mg/kg] were inhibited by vinpocetine [0.45-1.8 mg/kg, s.c.], but increased after piracetam [75-300 mg/kg, s.c.] in a dose-dependent manner. It is concluded that the nootropic drugs exert different effects on inflammation and gastric mucosal integrity in rats

Effect of the new anti-ischaemic drug "trimetazidine" on hepatic injury caused by carbon tetrachloride in rats

The effects of trimetazidine, a novel anti-ischaemic agent, on the development of hepatic injury induced in rats with carbon tetrachloride, were investigated. Hepatotoxicity was induced by CCl[4] orally [0.2 ml/kg followed by 0.1 ml/kg after one week]. Trimetazidine at three dose levels [3.6, 7.2 and 14.4 mg/kg], silymarin [25 mg/kg] and combination of trimetazidine [7.2 mg/kg] and silymarin [25 mg/kg] were administered orally daily for 15 days, starting at time of administration of CCL. The daily administration of trimetazidine conferred significant protection against the hepatotoxic effects of CCL, in rats. It decreased the increases in serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP] and also prevented the development of hepatic necrosis caused by CCL as determined 15 days after drug administration. Thus, compared with the CCL control group, serum ALT decreased by 35.1, 49.5 and 57%, AST by 28.2, 31.6 and 36% and ALP by 32, 39.7 and 40.6%, after the administration of trimetazidine at 3.6, 7.2 and 14.4 mg/kg, respectively. Silymarin administered alone, at the dose of 25 mg/kg reduced serum ALT by 30%, AST by 29.1% and ALP by 38.4% compared to CCL control. When silymarin was combined with 7.2 mg/kg of trimetazidine, the activities of ALT, AST and ALP were markedly decreased by 47.2%, 47.2% and 50.6%, respectively, compared with the CCl[4]control, indicating a beneficial additive effect. Histopathologic examination of the liver of rats treated with CCl[4] + trimetazidine showed less fibrosis compared with the CCl[4] -control group. Co-treatment with silymarin and trimetazidine, on the other hand resulted in marked histologic protection. It is concluded that the anti-ischaemic agent trimetazidine lessened hepatocellular injury caused by CCl[4], in rats, and had additive effect with silymarin. It was suggested, therefore, that trimetazidine alone or in combination with silymarin might have a place in the therapy of chronic liver diseases

Hepatic and renal toxicity of rifampicin and isoniazid in albino rats

Antituberculous drugs, rifampicin and isoniazid proved to be toxic to the liver and kidneys both biochemically and histopathologically when given singly in a dose of 5.4 mg/l00 gm body weight [b.wt] Intra peritoneally [I.P] twice weekly for two months and their toxic effect became more pronounced when given in combination.Isoniazid proved to be more toxic to the liver as reflected on hepatic enzymes [aspartate aminotransferase AST and alanine aminotransferase ALT] and kidney functions [serum creatinine and blood urea] compared to rifampicin Significant decrease in animals body weights compared to that of the controls was also pronounced with the combination, less with isoniazid and least with rifampicin but internal organs weights were not affected.After termination of therapy recovery of liver and kidney functions occured with rifampicin after one month, with isoniazid after two months and more than two months with the combination therapy

Modulation of the anti-inflammatory activity of aspirin, diclofenac and piroxicam in rats treated with oral contraceptive

The effect of oral contraceptives on the inflammatory process has been studied in two models; the carrageenan induced rat paw edema and granuloma formation. The percentage edema induced in oral contraceptive treated control was less than that induced in normal control. Also the granuloma weight was significantly reduced in oral contraceptive treated rats. The anti-inflammatory activity of aspirin, [20 mg/kg] diclofenac [5 mg/kg] in oral contraceptive treated rats was significantly less than that in normal rats