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Biomedical subjects

N S Parmar

Publications and source records attributed to N S Parmar.

At least 19 recordsLinked to original sources

Gastric and duodenal anti-ulcer activity of SKF 38393, a dopamine D1-receptor agonist in rats.

The effect of SKF 38393 (1-phenyl-7,8-diol-2,3,4,5-tetrahydro-1H-3-benzazepine), a specific dopamine D1-receptor agonist, was studied on pylorus-ligation and water immersion plus restraint stress-induced gastric ulcers, and cysteamine-induced duodenal ulcers in rats. Repeated administration of SKF 38393 (5 and 10 mg kg-1, p.o.) for six days was found to be effective in the prevention of gastric ulceration induced by water immersion plus restraint stress in rats. In 19-h pylorus-ligated rats, repeated treatment with SKF 38393 showed a significant reduction in the number and severity of ulcers. SKF 38393 did not alter the total gastric-mucosal carbohydrates:protein ratio; however, the gastric content volume and the free and total acidity were significantly reduced. In cysteamine-induced duodenal ulcers, the treatment with SKF 38393 for 6 days prevented the duodenal lesions. Our data suggests the involvement of dopamine D1 receptors in the anti-ulcer activity of SKF 38393, which could be largely attributed to its anti-secretory effect. Its anti-ulcer activity against water immersion plus restraint, also points towards a central mode of action, but its failure to alter the carbohydrate:protein ratio rules out any protective effect through the strengthening of the gastric mucosal barrier.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Gastric and duodenal anti-ulcer activity of sulpiride, a dopamine D2 receptor antagonist, in rats.

The gastric and duodenal anti-ulcer activity of sulpiride, a dopamine D2 receptor antagonist, was studied on various types of experimentally induced ulcers in rats, viz., pylorus ligation and water immersion + restraint stress-induced gastric ulcers, gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs and reserpine, and duodenal ulcers induced by cysteamine hydrochloride. It has been found to possess significant anti-ulcer activity against all these models. In 19 h pylorus ligated rats, it significantly reduced the gastric secretion, increased the fucose and sialic acid concentration of the gastric juice and reduced its protein content, thus increasing the total carbohydrate:protein (TC/PR) ratio. These results suggest that the antisecretory and gastric mucosal barrier strengthening effects of sulpiride may be responsible for its anti-ulcer activity. A central component also appears to be involved in its anti-ulcer action against water immersion + restraint stress model. The results of this study provide a rationale for its beneficial effect seen in the therapy of peptic ulcer disease.

Animals

Gastroprotective activity of ginger zingiber officinale rosc., in albino rats.

The cytoprotective and gastric anti-ulcer studies of ginger have been carried out in albino rats. Cytodestruction was produced by 80% ethanol, 0.6M HC1, 0.2M NaOH and 25% NaCl. Whereas gastric ulcers were produced by ulcerogenic agents including indomethacin, aspirin and reserpine, beside hypothermic restraint stress and by pylorus ligated Shay rat technique. The results of this study demonstrate that the extract in the dose of 500 mg/kg orally exert highly significant cytoprotection against 80% ethanol, 0.6M HC1, 0.2M NaOH and 25% NaCl induced gastric lesions. The extract also prevented the occurrence of gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs) and hypothermic restraint stress. These observations suggest cytoprotective and anti-ulcerogenic effect of the ginger.

Animals

Gastric anti-ulcer and cytoprotective effect of selenium in rats.

Selenium, a trace element, in the form of sodium selenite has been studied for its ability to protect the gastric mucosa against the injuries caused by hypothermic restraint stress, aspirin, indomethacin, reserpine, dimaprit, and various other gastric mucosal-damaging (necrotizing) agents in rats. The results demonstrate that oral administration of sodium selenite produces a significant inhibition of the gastric mucosal damage induced by all the procedures used in this study. Selenium, in a nonantisecretory dose, produced a marked cytoprotective effect against all the necrotizing agents. The cytoprotective effect of selenium against the effects of 80% ethanol and 0.6 M HCl was significantly reversed by prior treatment with a dose of indomethacin that inhibits prostaglandin biosynthesis. These data indicate that sodium selenite inhibits the formation of these lesions by the mucosal generation of prostaglandins. The concentrations of nonprotein sulfhydryls (NP-SH) were significantly decreased in the gastric mucosa following the administration of necrotizing agents--80% ethanol and 0.6 M HCl. Treatment with sodium selenite, which significantly reduced the intensity of gastric lesions, did not replenish the reduced levels of gastric mucosal NP-SH, thus ruling out the mediation of its protective effect through sulfhydryls. The antisecretory effect of sodium selenite, which becomes evident only in the high dose of 20 mumol/kg, may be responsible for the inhibition of gastric lesions induced by aspirin, indomethacin, reserpine, and dimaprit. Our findings show that selenium possesses significant anti-ulcer and adaptive cytoprotective effects. However, further detailed studies are required to confirm these effects, to establish its mechanism(s) of action, and to determine its role in the prophylaxis and treatment of peptic ulcer disease.

Administration, Oral

Cytological effects of khat (Catha edulis) in somatic and male germ cells of mice.

Cytological effects of khat (Catha edulis), a popular drug of abuse from Southern Arabia and Eastern Africa, have been studied in Swiss albino mice. The studies on the somatic system involved the use of micronucleus test and the cytological analysis of the mitotic index in the femoral cells of mice. In the micronucleus test, the mice were treated with different doses of khat extract (125, 250 and 500 mg/kg, p.o.) 30 and 6 hours before sacrificing the animals. The polychromatic erythrocytes were screened for the induction of micronuclei. For the analysis of bone marrow cytotoxicity, the mice were treated with the dose of 125, 250 and 500 mg/kg, body weight, p.o. daily for 5 consecutive days. The animals were sacrificed and the femoral cells were microscopically examined for the mitoses. Following the same schedule of treatment, studies on the cytogenetic analysis of meiotic chromosomal aberrations and the sperm head abnormality were undertaken. Khat extract significantly increased the frequency of micronucleated polychromatic erythrocytes, induced bone marrow depression and reduced the mitotic index of the somatic cells. It induced significant chromosomal aberrations viz., aneuploids, autosomal univalents, univalents of the sex chromosomes and polyploids. The frequency of abnormal sperms was also increased.

Animals

Gastric cytoprotection: a critical appraisal of the concept, methodology, implications, mechanisms and future research prospects.

Gastric cytoprotection is the property of certain substances, particularly prostaglandins, when used in non-antisecretory doses, to protect the gastric mucosa from becoming inflamed and necrotic on being exposed to noxious agents. An association between alterations in endogenous prostaglandins and gastric mucosal damage induced by a number of drugs has also been observed. The process of adaptive cytoprotection in which mild irritants protect the gastric mucosa against the damaging effects of various necrotizing agents has been shown to be prostaglandin mediated. However, the exact mechanisms underlying this cytoprotective activity have still not been elucidated although a number of hypotheses have been proposed. Recently, thromboxanes, leukotrienes and endogenous sulfhydryls have also been suggested to be involved in the pathogenesis of gastric mucosal damage induced by various necrotizing agents. This review attempts to provide an up-to-date appraisal of the concept, methodology, mechanisms and implications of this phenomenon and suggests that prostaglandins and endogenous sulfhydryls may play a significant role in the pathogenesis of gastric ulceration and may serve an important function in maintaining normal gastric mucosal integrity.

Animals

Clastogenic evaluation of cathinone and amphetamine in somatic cells of mice.

Clastogenic effects of cathinone, the active principle from khat (Catha edulis) and amphetamine, a compound having similar chemical structure and pharmacological activity, have been studied on the somatic cells of mice. Both of them produced marked clastogenic activity and affected the cell proliferation in the bone marrow of mice. They induced a significant increase in the frequency of micronucleated polychromatic erythrocytes at higher doses. These results substantiate our earlier observations on the clastogenic and mitodepressive activity of cathinone on the meristematic region of Allium cepa, and indicate that cathinone may be responsible for the mutagenic effect of khat reported by other workers. The clastogenic effects of amphetamine are being reported for the first time. Further studies are required to substantiate these findings and to study whether cathinone and amphetamine produce a direct clastogenic effect or whether they act as spindle poisons.

Alkaloids

Post-coital antifertility activity of the seeds of Coriandrum sativum in rats.

Effect of the aqueous extract of fresh coriander (Coriandrum sativum) seeds has been studied on female fertility in rats. Parameters included effects on oestrus cycle, implantation, foetal loss, abortion, teratogenicity and serum progesterone levels on days 5, 12 and 20 of the pregnancy. The extract at doses of 250 and 500 mg/kg orally produced a dose-dependent significant anti-implantation effect, but failed to produce complete infertility. Treatment of animals during day-8 to day-12 and day-12 to day-20 of the pregnancy did not produce any significant abortifacient activity. There was no significant change in the weight and length of the foetuses delivered by rats treated with the extract and no abnormalities were seen in the organs of the offsprings. The extracts produced a significant decrease in serum progesterone levels on day-5 of pregnancy which may be responsible for the anti-implantation effect observed in this study.

Abortifacient Agents

Proglumide, a cholecystokinin receptor antagonist, exacerbates alloxan-induced diabetes mellitus in Swiss mice.

The effect of proglumide ((+/-)-4-benzamido-N,N-dipropyl-glutaramic acid), a gastrin and cholecystokinin receptor antagonist, has been studied on the fasting plasma glucose (FPG) and insulin levels in normal and alloxan-diabetic mice. In normal mice, proglumide, administered as a single oral dose or twice daily for five consecutive days, did not produce any alteration in those parameters. Injection of alloxan monohydrate (70 mg kg-1 i.v.) produced a significant decrease in plasma insulin and a significant elevation of FPG levels on the 5th day after its administration as evidence of diabetes mellitus. Proglumide sodium, given as a single acute dose on the 5th day of alloxan injection, or as a twice daily dose for 5 days immediately after alloxan injection, significantly exacerbated the hyperglycaemia and further decreased the plasma insulin levels thus worsening the diabetogenic effect of alloxan. These observations point to a possible involvement of cholecystokinin (CCK) in alloxan-induced diabetes and indicate a need for monitoring the levels of FPG in diabetic patients being treated with a high dose of proglumide or other CCK-antagonists.

Animals

Evaluation of Artemisia inculta for anti-inflammatory activity in rats.

The ethanolic extract of Artemisia inculta has been screened for anti-inflammatory, analgesic and antipyretic activities on suitable experimental models. It has been found to produce significant inhibition of carrageenan induced paw edema and cotton pellet induced granuloma pouch and a significant decrease in the prothrombin time in rats. It failed to produce any analgesic or antipyretic activity on the hot plate reaction time and yeast induced hypyrexia tests in mice. It also did not produce any effect on the platelet aggregation and fibrinogen level in the rats. Amongst the phytoconstituents detected in this plant, flavonoids may be responsible for the observed anti-inflammatory effect of the ethanolic extract.

Animals

Effect of thromboxane A2 and leukotriene C4 inhibitors on the experimentally induced gastric lesions in the rat.

Effects of OKY-046, a thromboxane synthetase inhibitor; BM 13.177, a thromboxane A2-receptor antagonist and FPL 55712, a leukotriene antagonist have been studied on gastric lesions induced by necrotizing agents (80% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl and 100 mM sodium taurocholate), aspirin, indomethacin, reserpine and hypothermic restraint stress in rats. Ro 22-6923, a synthetic trimethyl prostanoid has been used for comparison. OKY-046, FPL 55712 and Ro 22-6923 produced dose dependent inhibition of gastric lesions induced by necrotizing agents and reduced the severity of aspirin, indomethacin, reserpine and hypothermic restraint stress induced lesions. BM 13.177 was not found effective against any of the models used in this study. These observations indicate towards the role of thromboxane A2 and leukotriene C4 in the genesis of gastric lesions induced by different methods. FPL 55712 required considerably lower doses than those of OKY-046 to display its protective effects in these models. Further studies on the levels of thromboxane A2 and leukotriene C4 in the gastric mucosa, are suggested to substantiate these observations.

Animals

Studies on the possible mechanism of morphine-induced potentiation of the gastroulcerogenic effect of indomethacin in rats.

Morphine has been shown to produce a significant potentiation of indomethacin-induced gastric lesions in rats. The exact mechanism of this response has still not been worked out. Hence, in the present study, the effects of pirenzepine, cimetidine, disodium cromoglycate, OKY-046 (a thromboxane A2 synthesis inhibitor), BM 13.177 (a thromboxane A2 receptor antagonist), FPL 55712 (a leukotriene C4 antagonist) and a synthetic trimethylprostanoid, Ro 22-6923 have been studied on the gastric ulcers produced by indomethacin and its combination with morphine in rats. Only naloxone, FPL 55712 and Ro 22-6923 significantly reduced the morphine-potentiated ulcerogenic response of indomethacin as compared to the indomethacin ulcers in the groups pretreated with these drugs. It is, therefore, proposed that the potentiating effect of morphine is mediated through the opiate receptors, which, in some way, increase leukotriene C4 and decrease prostaglandin-like activities in the gastric mucosa. Further studies on the levels of leukotriene C4 and endogenous prostaglandins are suggested to substantiate these findings.

Animals

Gastric and duodenal antiulcer and cytoprotective effects of proglumide in rats.

Proglumide has been studied for its ability to inhibit gastric secretion and to protect the gastroduodenal mucosa against the injuries caused by pyloric ligation, hypothermic restraint stress, acetic acid, nonsteroid anti-inflammatory drugs, reserpine, cysteamine and the cytodestructing agents: 80% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl and 30 mg of acetylsalicylic acid in 0.35 M HCl in rats. The results of this study demonstrate that proglumide has both prophylactic and curative effects on various experimentally induced ulcers. It produced a dose-dependent inhibition of gastric secretion in the pylorus-ligated rats and reduced significantly the intensity of gastric lesions induced by pyloric ligation, hypothermic restraint stress, acetic acid, mucosal damaging agents and that of duodenal ulcers induced by cysteamine. The intensity of gastric lesions induced by nonsteroid anti-inflammatory drugs and reserpine was also reduced significantly by proglumide. Cimetidine, which was used as a standard antiulcer drug for comparison, also produced a similar protective effect in most of the models used by us. It was found to have a more potent antisecretory effect but failed to protect the rats against the gastric mucosal damage induced by hyperthermic restraint stress and 0.2 M NaOH. Our findings suggest that proglumide exerts these antiulcer effects by its antisecretory, gastric mucosal resistance increasing and cytoprotective activities. Further studies are required to find out its exact mechanism of action and therapeutic usefulness.

Animals

Studies on the gastroulcerogenic effects of pylorus ligation, hypothermic restraint stress, aspirin, indomethacin and reserpine in morphine dependent rats.

The gastric mucosal damage induced by pylorus ligation for 6 h, hypothermic restraint stress, aspirin, indomethacin and reserpine was studied in morphine dependent rats. Morphine tolerance and dependence were produced by administering the gradually increasing concentrations of morphine sulphate in drinking water for 21-24 days. The tolerance and dependence produced by morphine were confirmed by a decreased analgesic response to morphine in the hot plate test and by producing a naloxone precipitated withdrawal syndrome respectively. The intensity of gastric mucosal damage induced by pylorus ligation, aspirin and indomethacin was significantly higher in morphine dependent rats than that observed in the naive animals. Studies on the gastric secretion did not reveal any significant change in the volume of gastric secretion, titrable acidity and gastric output of 6 h pylorus ligated rats. The average lesion scores in the reserpine treated and hypothermic restraint stressed rats were not significantly different from those obtained in the naive animals. Further studies are required to establish the exact mechanisms underlying these observations.

Animals

Studies on ethanol and/or nicotine induced acute changes in the levels of plasma amino acids and other biochemical parameters of male Wistar rats.

The effects of acute administration of ethanol and nicotine either singly or in combination, have been studied on the plasma amino acids levels and certain biochemical and hematological parameters in the rats. Both ethanol and its combination with nicotine produced significant reduction in the levels of a number of amino acids and the total amino acid pool. Only the levels of taurine and hydroxyproline were increased in the ethanol treated rats, whereas its combination with nicotine resulted in markedly elevated levels of hydroxyproline, ornithine and taurine. These changes were also accompanied by a significant rise in blood glucose, ALT, AST, blood urea and uric acid and a significant reduction in the total protein and triglycerides levels. Nicotine by itself produced less profound effect on the plasma amino acids and other biochemical parameters.

Alanine Transaminase

Anti-inflammatory activity of the flavonoid fraction of khat (Catha edulis Forsk).

The administration of the flavonid fraction, isolated from Khat (Catha edulis Forsk), in a dose of 200 mg/kg orally, produced a significant anti-inflammatory activity against the carrageenan induced paw oedema and cotton pellet granuloma in albino rats. The results were comparable with the standard anti-inflammatory drug oxyphenbutazone.

Animals

Anti-inflammatory activity of Commiphora molmol.

The petroleum ether extract of the oleo-gum resin of Commiphora molmol, at a dose of 500 mg/kg body weight, produced significant inhibition of carrageenan induced inflammation and cotton pellet granuloma. The extract also showed significant antipyretic activity in mice. Further studies on the fractionation of phytoconstituents and their mechanism of action are in progress.

Animals

Anti-inflammatory activity of some Saudi Arabian medicinal plants.

Five plants which have been used for the treatment of rheumatism, arthritis and gout in the traditional medicine of Saudi Arabia, were evaluated for their anti-inflammatory properties. Of these the ethanolic extract of Capparis decidua and the aqueous extract of Capparis spinosa were found to possess significant anti-inflammatory activity against carrageenan induced oedema in rats. These two plants were also tested for their antipyretic and analgesic activity. C. decidua was found to possess significant antipyretic effect. Both of them are devoid of analgesic activity.

Animals