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Biomedical subjects

A M Ageel

Publications and source records attributed to A M Ageel.

At least 19 recordsLinked to original sources

Toxicity studies in mice of common spices, Cinnamomum zeylanicum bark and Piper longum fruits.

Acute (24 hours) and chronic (90 days) oral toxicity studies on the ethanolic extracts of common spices Cinnamomum zeylanicum Nees bark and Piper longum L. fruits were carried out in mice. Acute dosages were 0.5, 1.0 and 3 g/kg while the chronic dosage was 100 mg/kg/day. All external morphological, hematological and spermatogenic changes, in addition to body weight and vital organ weights, were recorded. The extracts of both the plants caused no significant acute or chronic mortality compared to the control during this study. During chronic treatment there was no significant change in the pre- and post treatment body weight of the test animals while the weight gain in the control group was significant. C. zeylanicum treatment caused reduction in liver weight while P. longum caused a significant increase in the weight of the lungs and spleen of the treated animals compared to the control. Hematological studies revealed a significant fall in hemoglobin level of C. zeylanicum treated animals. Both of the extracts induced a significant increase in reproductive organ weights, sperm motility, sperm count and failed to illicit any spermatotoxic effect.

Animals

Biochemical basis of sodium valproate hepatotoxicity and renal tubular disorder: time dependence of peroxidative injury.

Mice fed with sodium valproate for 7, 14 and 21 days were evaluated for hepatotoxicity and renal tubular disorder. The drug was administered as an aqueous solution with an increasing concentration up to five days gradually reaching up to 0.71% w/v, which persisted throughout the study period. Mice fed with sodium valproate for 7, 14 and 21 days showed, marked hepatic injury and renal tubular disorder, evidenced by increased levels of malondialdehyde as a measure of lipid peroxidation. Administration of sodium valproate affected the glutathione contents both in liver and kidney tissue at all the three time points. However, this reduction in glutathione concentration was more pronounced in kidney when compared to control group. These results support the hypothesis that lipid peroxidation mediates the effect of sodium valproate on liver and kidney. Furthermore, the valproate induced toxicity is time related and the increase in lipid peroxide levels and depletion of glutathione occur time dependent even if the dose is clinically appropriate.

Animals

Evaluation of the antiinflammatory activity of sodium valproate in rats and mice.

1. Treatment of rats with sodium valproate (100, 200 and 400 mg/kg i.p.) reduced the paw oedema induced by carrageenan by 36, 15 and 48%, respectively, within 3 h . 2. The effect produced by the higher dose (400 mg/kg) was equivalent to that produced by indomethacin (100 mg/kg). At 100 and 400 mg/kg, sodium valproate decreased the granuloma formation by a significant level. Similar doses of sodium valproate did not affect the rectal temperature in yeast-fevered mice, except with a dose of 200 mg/kg, which showed a significant decrease at 180 and 240 min posttreatment. 3. In comparison, sodium salicylate reduced the hyperthermia very significantly throughout the study period. 4. In normothermic mice, the rectal temperature changed only with a 400 mg/kg dose, but did not respond to lower SV doses. 5. The results indicate that sodium valproate, useful clinically as an epileptic drug, may have a potential therapeutic use as a mild antiinflammatory agent.

Animals

Effect of (-)-cathinone, a psychoactive alkaloid from khat (Catha edulis Forsk.) and caffeine on sexual behaviour in rats.

The effect of (-)-cathinone, caffeine and their combinations was studied on the sexual behaviour of male rats. Male sexual activities were assessed by recording the erectile responses (grooming of genitalis, yawning/stretching and homosexual mounting), in the absence of females. The copulatory behaviour was observed by caging males with receptive females brought into oestrus with s.c. injection of oestradiol benzoate and progesterone. The copulatory pattern of male rats (mounting, intromissions, ejaculations and refractory period) was recorded. The oral treatment of cathinone (5 mg kg-1 day-1), caffeine (50 mg kg-1 day-1) and their combinations for 15 days increased arousal (motivation) in male rats as evidenced by increased mounting performance and anogenital investigatory behaviour. However, erectile and ejaculatory responses, measured in the present study, showed no stimulant effect. It is conceivable from the present results that cathinone, the psychostimulant constituent of khat modified masculine pattern behaviour and caffeine also changed the effect of cathinone when administered concomitantly. However, our data provide no evidence that cathinone could be considered as an aphrodisiac.

Administration, Oral

Comparative skin testing with PPD tuberculin, Mycobacterium avium and M. scrofulaceum sensitin in schoolchildren in Saudi Arabia.

SETTING: Jizan region, Saudi Arabia. OBJECTIVE: To test methodology for studies of tuberculin sensitivity and effectiveness of BCG vaccination programme. DESIGN: School children (n = 315) aged 6-12 years simultaneously tested intradermally with PPD tuberculin RT23, 2TU and 0.1 microgram Mycobacterium avium or M. scrofulaceum sensitin. Presence of BCG scar as evidence of previous BCG vaccination. Cervical lymph nodes palpated. RESULTS: BCG coverage was 75%. The prevalences of positive reactions (induration > or = 6 mm) were higher among children with than without scar. Prevalences of positive reactions to PPD and M. scrofulaceum sensitin were higher among girls than boys. In children with scar, the mean size of positive reactions to PPD was larger among girls than boys, and the prevalence of positive reactions was smaller in this group among children with than without palpable cervical lymph nodes. The sizes of reactions both to M. avium and to M. scrofulaceum sensitin were correlated to the size of the tuberculin reactions. Previous admission to hospital was reported less often by children with than without scar. CONCLUSIONS: The technique applied and training of staff was satisfactory. In further studies, however, we will apply three simultaneous tests to each person.

Age Factors

The quipazine- and TFMPP-increased conditioned avoidance response in rats: role of 5HT1C/5-HT2 receptors.

The role of serotonin (5-HT) in the acquisition of the conditioned avoidance response was investigated. The effects of different serotonin agonists and antagonists, administered prior to learning sessions, were studied in groups of naive rats using the two-way shuttle box. Quipazine, an agonist at 5-HT1B/1C/2 receptors, significantly increased avoidance responding in a dose-dependent manner (1.25-10 mg/kg, s.c.). The putative 5-HT1B/1C receptor agonist TFMPP (1-[m-trifluoromethylphenyl] piperazine) at doses of 1.25 and 2.5 mg/kg (s.c.), increased acquisition of conditioned avoidance but showed no significant difference from control at doses of 5 and 10 mg/kg. The 5-HT1A agonist, buspirone, significantly decreased acquisition of conditioned avoidance. Increased acquisition of conditioned avoidance induced by either quipazine or TFMPP was effectively antagonized by the mixed 5-HT 1C/2 receptor antagonists, ketanserin (0.2 and 2 mg/kg, s.c.) and mianserin (1 mg/kg, s.c.). In contrast, spiperone (5-HT1A/2 receptors antagonist: 0.2 mg/kg, s.c.) only inhibited the increased acquisition induced by TFMPP. On the other hand, the 5-HT1A/1B receptors antagonist, pindolol, failed to antagonize the increase in acquisition of conditioned avoidance caused by quipazine or TFMPP. These results suggest that quipazine increases the conditioned avoidance behaviour by an action that might be mediated through stimulation of 5-HT1C receptors. The acquisition of conditioned avoidance induced by TFMPP, which was blocked by ketanserin, mianserin and spiperone but not by pindolol, suggests the involvement of 5-HT1C/2 receptors in the action of TFMPP.

Animals

Protective effect of Swertia chirata against indomethacin and other ulcerogenic agent-induced gastric ulcers.

The effect of Swertia chirata has been studied on experimentally induced gastric ulcers in rats. The ethanolic extract of chirata significantly reduced the intensity of gastric mucosal damage induced by indomethacin and necrotizing agents. It produced a significant decrease in gastric secretion in pylorus-ligated rats. The extract inhibited acetylcholine-induced contraction of guinea pig ileum, suggesting its anti-cholinergic activity. Pretreatment of rats with the extract significantly prevented ethanol-induced gastric wall mucus depletion and restored the non-protein sulfhydryl (NP-SH) content in the glandular stomachs. These findings support the use of chirata for the treatment of gastric ulcers in traditional medicine.

Animals

Effect of praziquantel and oxamniquine on prostacyclin synthesis by the rat arterial and myometrial tissues.

1. The influence of the two antischistosomal drugs (+/-) praziquantel and (+/-) oxamniquine on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium in vitro was investigated using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with praziquantel (64-512 microM) or oxamniquine (36-288 microM) for 30 min at 37 degrees C significantly inhibited basal PGI2 synthesis in a concentration-dependent manner (P less than 0.005, n = 5-6). 3. Both drugs failed to inhibit PGI2 synthesis in presence of exogenous arachidonic acid (AA) (16.6 microM). 4. Furthermore, they did not antagonize AA (4 nmol kg-1)-induced hypotension in urethane-anaesthetized rats. Thus, the drugs seemed to act via inhibition of phospholipase A2 enzyme (PLA2). 5. The highly lipophilic drugs may interact with membrane phospholipids resulting in prevention of interaction between the substrates and the enzyme's active site.

Animals

Toxicity studies on Alpinia galanga and Curcuma longa.

Acute (24 h) and chronic (90 days) oral toxicity studies on the ethanolic extracts of the rhizomes of Alpinia galanga and Curcuma longa were carried out in mice. Acute dosages were 0.5, 1.0, and 3 g/kg body weight while the chronic dosage was 100 mg/kg/day as the extract. All external morphological, hematological, and spermatogenic changes, in addition to body weight and vital organ weights were recorded. During this investigation no significant mortality as compared to the controls was observed. The weight gain in the A. galanga treated animals was significant as in the control group while the C. longa-treated animals gained no significant weight after chronic treatment. C. longa treatment induced significant changes in heart and lungs weights upon chronic treatment. Hematological studies revealed a significant rise in the RBC level of A. galanga-treated animals and a significant fall in the WBC and RBC levels of the C. longa-treated animals as compared to the controls. The gain in weights of sexual organs and increased sperm motility and sperm counts were observed in both groups of extract-treated male mice, however, these changes were highly significant in the A. galanga-treated group. Both extracts failed to show any spermatotoxic effects.

Animals

Effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanol amines on the spontaneous and evoked contractions in the rat isolated uterus.

1. The effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanol amine (compounds M & E), respectively and diltiazem (D) were examined on the spontaneous and evoked uterine contractions of pregnant rats in vitro. 2. Addition of compound M (75-300 microM), compound E (15-60 microM) or D (100-400 nM) to the uterine tissues, inhibited the spontaneous contractions in a dose-dependent manner. The potency order was D greater than E greater than M. 3. The inhibitions were reversed by elevating the extracellular Ca2+ concentration by 20 mM. The compounds also antagonised CaCl2-evoked contractions. 4. Treatment of rats with either compound during pregnancy days (1-16) did not affect the implantation process and did not induce any teratogenicity. 5. The uterine inhibitory effects of the compounds may be due to blockade of uterine Ca2+ channels.

Animals

Influence of diethylcarbamazine and mefloquine on PGI2 synthesis by the rat thoracic aorta and myometrial tissues.

1. The influence of the antifilarial drug diethylcarbamazine citrate (D) and DL-erythro mefloquine hydrochloride (Mf) on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium was investigated in vitro using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with D (25.5-204 microM) or Mf (24-192 microM) for 30 min at 37 degrees C significantly inhibited PGI2 synthesis in a concentration-dependent manner. 3. D exhibited its inhibitory effect even in presence of exogenous arachidonic acid (AA) (16.6 microM) whereas Mf lost its inhibitory effect in presence of AA. 4. Pretreatment of urethane-anaesthetized rats with D (32 mumol kg-1) but not Mf (7.5 mumol kg-1) for 30 min significantly antagonized AA (4 nmol kg-1)-induced hypotension. 5. Furthermore, D (0.25-0.5 microM) antagonized AA-induced aggregation in rabbit platelet-rich plasma without affecting that of ADP. 6. D seemed to interfere with the action of the PG endoperoxide synthase (PG cyclooxygenase) whereas Mf seemed to interfere with the action of phospholipase A2 (PLA2) enzyme. 7. D may have exerted its effect via release of toxic O2 radicals whereas Mf effect may have been due to an interaction with PLA2 substrate phospholipids. 8. The demonstrated inherent property of these two drugs to inhibit the synthesis of the potent vasodilator, platelet antiaggregatory, anticonvulsant and antiinflammatory mediator PGI2 may partly contribute towards better understanding of the biochemical mechanisms that underly some of the previously known but poorly understood actions of these drugs.

Adenosine Diphosphate

Toxicity studies in mice of ethanol extracts of Foeniculum vulgare fruit and Ruta chalepensis aerial parts.

Acute (24-h) and chronic (90-day) oral toxicity studies on the ethanolic extracts of Foeniculum vulgare fruit and Ruta chalepensis aerial parts were carried out in mice. Acute dosages were 0.5, 1.0 and 3 g/kg while the chronic dosage was 100 mg/kg per day of extract. All external morphological, haematological and spermatogenic changes, in addition to body and vital organ weights were recorded. The extracts caused no significant acute or chronic mortality as compared to controls during this investigation. The treated male mice gained significant weight during chronic treatment while a loss or no significant change in weight was noticed in the female mice treated with the same extracts. Haematological studies revealed a significant fall in RBC level of R. chalepensis-treated animals. Both the extracts failed to show spermatotoxic effects.

Animals

Influence of chemotherapeutic agents on prostacyclin synthesis. II. Effects of tetracycline and penicillin G on prostacyclin synthesis by the rat thoracic aorta and myometrial tissues.

The influence of the two antibiotics tetracycline hydrochloride (T) and penicillin G sodium (P) on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium was investigated in vitro using a rat platelet antiaggregatory bioassay method. Pretreatment of the tissues for 30 min at 37 degrees C with T (21-168 microM) or P (28-224 microM) significantly inhibited PGI2 synthesis in absence or presence of exogenous arachidonic acid (AA) (16.6 microM), (P less than 0.01, n = 5-6). Furthermore, pretreatment of rats with the two drugs (T 11 and P 175 mu mole kg-1 for 30 min) significantly antagonised AA (4 n mole kg-1)-induced hypotension in urethane-anaesthetised rats. They also (T 0.5-4 and P 1-6 microM) antagonised AA-induced aggregation in rabbit citrated platelet-rich plasma. T failed to affect ADP-induced aggregation to any significant level whereas P (3-6 microM) reduced ADP-induced aggregation. The drugs seemed to interfere with the action of the PG endoperoxide synthase (or PG cyclooxygenase) enzyme resulting in decreased formation of PGG2 and PGH2. Such an effect may have resulted from the induced formation of toxic [OH-] radicals and/or inhibition of O2 uptake by the tissues under the influence of the drugs. The demonstrated inherent property of these two antibiotics to inhibit the synthesis of the potent vasodilator, platelet antiaggregatory, anticonvulsant and inhibitor of gastric acid secretion--PGI2, may partly contribute towards better understanding of the biochemical mechanisms that underlie some of the previously known but poorly understood actions of these antibiotics. Furthermore, since good evidence exists for the involvement of excessive uterine prostaglandin synthesis in dysmenorrhoea and premature deliveries, it is suggested that the potential benefits of T or P in these two disorders be investigated.

Animals

The toxicity of Catha edulis (khat) in mice.

A large number of people in East Africa and Southern Arabia chew khat leaves because of its pleasurable and stimulating effects. Due to its habit forming property, the khat has been classified as a "Substance of Abuse" by the World Health Organization. In view of the large number of medical problems reported in khat chewers, the present study was undertaken to investigate the chronic toxicity of khat in mice. Three groups of mice were treated with aqueous solution of khat extract in the dose of 50, 100, and 200 mg/kg. body weight daily by oral intubation route for 6 weeks. The results indicated a dose-dependent decrease in body weight, an increase in the incidence of mortality and induction of site specific body and eye lesions. The histopathological examination of the lesions revealed reactive hyperplasia and necrosis in the lymphoid tissues. The necrotic areas in the subcutaneous tissues showed the presence of numerous polymorphs.

Animals

Pharmacological studies on aerial parts of Calotropis procera.

The decoction of the aerial part of Calotropis procera is commonly used in Saudi Arabian traditional medicine for the treatment of variety of diseases including fever, joint pain, muscular spasm and constipation. The present investigation was undertaken to confirm its claimed activity in traditional medicine. The ethanol extract of the plant was tested on laboratory animals for its antipyretic, analgesic, anti-inflammatory, antibacterial, purgative and muscle relaxant activities. The results of this study showed a significant antipyretic, analgesic and neuromuscular blocking activity. On smooth muscle of guinea pig ileum, the extract produced contractions which was blocked by atropine supporting its use in constipation. The extract failed to produce significant anti-inflammatory and antibacterial activities. Our phytochemical studies on the aerial parts of C. procera showed the presence of alkaloids, cardiac glycosides, tannins, flavonoids, sterols and/or triterpenes. However, the chemical constituents responsible for the pharmacological activities remains to be investigated. The safety evaluation studies revealed that the use of extract in single high doses (up to 3 g/kg) does not produce any visible toxic symptoms or mortality. However, prolong treatment (90 days) causes significantly higher mortality as compared to control group.

Animals

An evaluation of the male reproductive toxicity of cathinone.

(-)-Cathinone is the major psychoactive component of khat plant (Catha edulis Forssk.). Khat has been shown to produce reproductive toxicity in human beings and experimental animals. However, the chemical constituents of khat leaves responsible for sexual dysfunction are not known. In the present study cathinone enantiomers have been investigated for their reproductive toxicity in rats. Cathinone produced a dose-dependent decrease in food consumption and suppressed the gain in body weight. There was a significant decrease in sperm count and motility and increase in the number of abnormal sperms in cathinone treated animals. Histopathological examination of testes revealed degeneration of interstitial tissue, cellular infiltration and atrophy of Sertoli and Leydig's cells in cathinone treated animals. Cathinone also produced a significant decrease in plasma testosterone levels of the rats. Although both enantiomers of cathinone produced deleterious effects on male reproductive system, (-)-cathinone was found to be more toxic. From this study it may be concluded that the cathinone content in khat may be partially or totally responsible for the reproductive toxicity in khat chewers.

Alkaloids

The induction of dominant lethal mutations upon chronic administration of khat (Catha edulis) in albino mice.

The mutagenicity of a methanolic extract of khat has been evaluated on male germ cells using the dominant lethal test in albino mice. An aqueous solution of khat extract was administered orally in doses of 50, 100 and 200 mg/kg body wt., respectively, to 3 different groups of male mice for a period of 6 weeks. At the end of treatment each male mouse was allowed to mate with 2 different groups of 3 females each, on 2 consecutive weeks. These females were necropsied on the 13th day of their presumptive mating, and the number of implants in each female and the ratio of live and dead embryos were determined. The results of this study showed that the treatment of male mice over a period of 6 weeks produced a dose-dependent reduction in the rate of fertility in the first week after mating, which was irreversible in the second week at the highest dose (200 mg/kg). Khat extract also induced post-implantation loss during the first week following treatment. However, a comparison of the results of the first and second weeks showed a reversible pattern of dominant lethality.

Animals

Preliminary toxicity studies on ethanol extracts of the aerial parts of Artemisia abyssinica and A. Inculta in mice.

Ethanolic extracts of the aerial parts of Artemisia abyssinica and A. inculta were subjected to acute toxicity observations in mice for 24 h and chronic toxicity evaluation for 3 months. External morphological changes, visceral toxicity, haematological changes, spermatogenic dysfunction and effect on body weight and vital organ weight were recorded. In both the chronically treated groups, no significant acute mortality was observed up to 3 g/kg p.o. There was no weight gain in A. abyssinica chronically-treated mice while the weight gain of A. inculta-treated animals matched that of the control group. Significant sperm damage was observed in A. abyssinica-treated mice while A. inculta failed to produce any significant spermatotoxic effect.

Alopecia