Effect of fresh garlic homogenate [FGH] on rat heart after exposure to hot water immersion stress

The present study aims to investigate the possible cardioprotective role of garlic on adult male Sprague-Dawely albino rats after stress exposure. Animals were exposed to stress by immersion in hot water for one day, one week and three weeks of stress. The myocardial activity was evaluated by estimating ECG, heart to body weight ratio, serum creatine phosphokinase [CPK-MB] activity, antioxidant enzymes activities, as well as histopathological alterations in cardiac muscle. Garlic was administered to the animals at a dosage of 250 mg/kg b.w.. Exposure for one day stress was of weak effect, while one week and three weeks of stress exposure were nearly of the same effect, causing significant changes in ECG, cardiac hypertrophy, elevation in serum CPK [MB] activity, significant decrease in the antioxidant enzyme activities and increase in MDA content, and significant alterations in histopathological analysis when compared with control. Supplementation of garlic [250 mg/kg b.w.] orally for one day stress exposed and one week stress exposed animals could not produce any significant change when compared to untreated stress exposed animals. However, after 28 days aqueous garlic homogenate supplementation has significantly improved ECG, decreased cardiac hypertrophy, decreased serum CPK [MB] activity, increased all the antioxidant enzyme activities and decreased MDA content as well as improved the myocardial histopathology compared the three weeks stress exposed group. The results indicated that stress exposure affects the myocardial function through direct effect: on the heart muscle, leading to arrhythmia and hypertrophy, and indirect effect: by generating free radicals and oxidative stress

Optimization of the sensitivity of the forced swimming technique for evaluating the antidepressant effect of drugs

Biphenyl Dimethyl Dicarboxylate [DDB] is attracting a growing attention for its pharmacotherapeutic properties as a protector against viral and chemical hepatotoxicity, and possibly as an immunomodulator. It has been also shown to possess some neurobehavioral effects on laboratory animals. Thus, the rising wide spread use of DDB, together with the demonstration of its neurobehavioral potential; have stimulated our interest to investigate its effect on the state of depression. The present work was designed to study the effect of combination of tail suspension and forced swimming techniques on the state of depression, and to compare the effect of fluoxetine and DDB on the combined technique. In addition, serotonin [5-HT], dopamine [DA] and norepinephrine [NE] contents were assayed in the whole brain in each case. The study was carried out on adult male mice. Fluoxetine was administered as a single dose [15 mg/kg, i.p.] and DDB was administered daily for 7 consecutive days [100 mg/kg/day, p.o.]. The obtained results showed that DDB exerted similar effect on immobility time as fluoxetine. However, it produced different neurochemical effects

study of the possible influence of biphenyl dimethyl dicarboxylate [DDB] on the social behavior developed by the sensory contact model in mice

The sensory contact model allows forming different psychopathological states produced by repeated agonistic interactions in male mice. It gives the opportunity of using animals with behavioral pathology to investigate the action of novel [along with widely used] psychotropic drugs and to conduct their screening in the simulated clinical conditions. Due to wide use of Biphenyl Dimethyl Dicarboxylate [DDB] together with its neurobehavioral effect, the present work aimed to investigate the possible effects of DDB on social behavior by studying its protective and medicative effects on the process of transformation to aggressive and submissive behaviors using the sensory contact model. Besides, measuring behavioral changes [using the open field test and the elevated plus maze test], neurotransmitters [serotonin, norepinephrine, and dopamine] and immunological changes [total leucocyte count, differential leucocytic count, and evaluation of bone marrow lymphocytes count and viability assessment] were evaluated. The work was conducted using adult male Swiss mice. DDB was administered orally in a dose of 100 mg/kg/day for two weeks and in two regimens. First as a protective treatment: it was applied for two weeks from the fifth day to the last day of the sensory contact model. Second, as a medicative treatment: DDP was administered after the end of the sensory contact model where the animals were kept in comfortable housing condition without daily interaction and received the treatment for two weeks. The present results concluded that, administration of DDB to the sensory contact model involved animals was showen to be associated with significant impacts on the animals' behavior, brain contents of neurotransmitters as well as the examined immunity related parameters. The produced effects were developed on the frame of DDB administration, whether it is administred as a possible protective agent or as a possible medicative one

Neurobehavioral effects of biphenyl dimethyl dicarboxylate in rats

The present study aimed at evaluating the possible potential of DDB to affect behavior and exploring the corresponding changes in brain monoamines levels. The work was conducted using adult male Sprague-Dawely rats. Animals were classified into three groups. Group I given a relatively low dose [50 mg/Kg] of DDB, group II given a higher dose [100 mg/Kg] of DDB, while group III given vehicle and served as control. Doses were given daily along 14 consecutive days using an oral gavage. The estimated behavioral parameters were locomotion and neuromuscular co-ordination [open field test and swimming test], exploration and curiosity [evasion test], learning and memory [conditioned avoidance response], depression and despair [forced swimming test], aggressive behavior and sociability [isolation technique, home cage observation and resident intruder paradigm]. In addition, brain monamines levels, namely Dopamine [DA], Norepinephrine [NE] and Serotonin [5-HT] were evaluated in various brain regions spectrophotoflourimetrically. DDB clearly affected animals' behavior, manifested by significant increase of locomotor and exploratory activities with a parallel enhancement of cognition, learning and memory. In addition, DDB possessed a positive effect on the animals' aggressiveness and hostility, which was correlated with significant modifications of monoamines levels in various brain regions, especially DA and NE levels. The obtained results show that DDB possesses a significant potential as a behaviorally active drug. They point to the possibility of using DDB as a tonic and/or stimulant medication to enhance motor co-ordination, cognition and memory. Furthermore, DDB might be clinically valuable as an anxiolytic or antidepressant treatment according to the dose administrated

study of the pharmacotherapeutic amelioration of the victims of aggression in mice

The sensory contact model [SCM] allows production of alternative types of social behavior [aggressive or submissive] in male mice. The aim of the present work was to validate the ability of the SCM by comparing the resulting groups of animals using a behaviorally relevant test [open field test] and to assess the effect of caffeine on the behavior of the defeated subjects. Caffeine [10 mg/Kg i.p] was given to the defeated mice daily for 15 consecutive days, just after the social conflict session. Animals were then introduced to the open field test [OFT]. In addition, total weight gain was also evaluated. Results showed a significant decrease in the body weight of the defeated mice that was partially compensated in mice received caffeine. In the OFT, defeated mice showed significant decrease in the ambulation, rearing, defecation and time spent in the centre of the arena. Such decrease was partially compensated by administration of caffeine while aggressive animals demonstrated a distinctive behavioral pattern. The obtained results demonstrated the ability of the SCM to obtain subjects with different behavioral patterns and also the partial potential of caffeine to diminish the negative effects of social defeat on animals' behavior

Influence of biphenyl dimethyl dicarboxylate [DDB] on social play behavior of young rats

Biphenyl Dimethyl Dicarboxylate [DDB] is a synthetic analogue of schisandrin C, a component of Fructus schisandrae. It is a widely prescribed agent for the improvement of liver function of hepatitis patients and has been recently proved to possess immunomodulatory properties. In our earlier work, DDB was shown to interfere with behavior. The present work was to assess the possible effect of DDB on the play behavior. The study was carried out on young Sprague Dawley Rats. DDB was administered orally for seven consecutive days [100mg/kg/day]. Animals were isolated for about 28hr before the day of the experiment. Each pair was placed in an aquarium glass cage where the play behavior of a pair of animals was recorded by a special Infrared Video Camera allowing super night shots, for 25 min. Three major categories were assessed, namely "play social behavior", "non-play social behavior" and "non-social behavior". DDB was found to affect the play behavior of the partner rat where the "pounce on" and "pinning" were significantly increased. Parallel changes in brain NE were found. In conclusion, DDB was shown to change the play behavior of the partner rat

immunomodulatory effects of nigella sativa oil in protein malnourished mice

The present study aims at evaluating the immunomodulatory effects of Nigella sativa oil [NSO] in protein malnourished mice. Protein malnutrition [PM] was induced by keeping mice at nourishment with standard synthetic diet containing 8% casein content, while normally fed mice received 20% casein diet. NSO was given daily by the oral route, along two weeks in two dose levels [50mg/kg and 100 mg/kg]. It was found to restore the PM reduced relative weights of thymus, liver and spleen, as well as the induced decrease in total leucocytic count [TLC] which was expressed in reductions of lymphocytes and eosinophils count. Moreover, NSO could counteract the PM induced lowering in opsonophagocytic activity as indicated by lowering the phagocytosis percent as well as phagocytic and opsonophagocytic indices. In addition, the PM caused decline in both serum IgG and IgM, where only that of IgG was alleviated under the influence of NSO. The used high dose of NSO could correct the PM induced reduction in bone marrow lymphocytes count. The obtained data indicate that NSO possesses immunomodulatory actions and that it may be regarded as a candidate drug for counteracting the adverse immunological consequences that are induced by PM

study on the possible doxycycline-ginkgo biloba extract phototoxic interaction in mice

Doxycycline is considered as the most phototoxic drug in tetracycline group. Its phototoxic potential has been demonstrated in human being as well as in laboratory animals. The aim of the resent work was to evaluate the possible protective effect of Ginkgo biloba extract, against doxycycline-induced phototoxicity. The study was performed on Swiss albino mice. Doxycycline [400 mg/kg] was administered orally. Two dose levels of Ginkgo biloba extract were utilized [100 and 200 mg/kg p.o.]. Mice were exposed to UV-A radiation one hour after administration of doxycycline. UV-A radiation was directed to the animal's ears for 210 min. at a dose of 25 Jol/cm[2]. Immediately after irradiation, animals were given a single dose of Ginkgo biloba extract. Twenty four hours later, the erythmatous photoreaction was examined by the naked eye according to a score index. Edema was evaluated by measuring ear pinna thickness using digital micrometer. Ears were then excised and subjected to histopathological evaluation. The obtained results showed significant protection by Kingo biloba extract against doxycycline-induced phototoxicity. The protection was dose dependent, where each of erytherma and ear pinna thickness were reduced by 33% and 44%, and 28% and 39% following the low and high used doses of Ginkgo biloba extract, respectively

bioequivalence study on two preparations of furosemide in health volunteers

The two products under evaluation as a test and reference were found to be pharmaceutically equivalent. They were subjected for in vivo evaluation in healthy volunteers for furosemide plasma levels, and urinary levels and excretion rate of sodium where the computed relative bioavailability were 98.36% and 93.45% for furosemide plasma levels and urinary excretion of sodium, respectively. The needs and advantages of utilizing sodium determination in urine as an adjunct for bioequivalence measurements were discussed

bioequivalence study on glafenine tablets in normal volunteers

The in vivo availability study has been performed on reference and test products of glafenine 200 mg tablets. The study was based on urinary excretion of glafenic acid in nine healthy volunteers. The given dose [400 mg] was administered according to a cross over design with 10 days as a washout interval. Tmax, Cmax and AUC of glafenic acid in urine demonstrated the possible bioequivalence of preparation under evaluation. The present work proposed the utility of use of optical density index [instead of glafenic acid concentration] for computation of the pharmacokinetic parameters

Comparative evaluation of the bio-efficacy of sucralfate products in laboratory animals

The present work introduced an experimental biological approach for comparative assessment of bioequivalency of sucralfate products. The therapeutic effect of sucralfate depends on its ability to form an adherent and protective layer at the site of ulceration. Two complementary experiments were utilized: Evaluation of healing of neurogenically produced gastric ulcers in rats, and estimation of aluminum in the sucralfate protective layer at the linings of the gastrointestinal tract in rabbits suffering from mechanically produced gastric ulcers. Sucralfate was administered twice daily for seven days post-ulcer indication. The dose for rats was 285 mg/10 ml water/kg. The dose for rabbits was 0.5 g [0.5 tablet] per animal. Two commercially available products were compared. The applied approach was found useful in assessment of bioequivalence of sucralfate products. A major advantage was the utilization of therapeutically relevant pharmacodynamic quantifiable measures by use of laboratory animals

Comparative percutaneous absorption of diclofenac emulgel preparations in normal volunteers

The bioequivalency of two diclofenac emulgel test products in comparison to diclofenac emulgel as a reference product were evaluated. The three products were nearly pharmaceutically equivalent. The comparative bioavailabilities of diclofenac were assessed using the drug plasma levels as a basic indicator. Twenty-one healthy volunteers were participated in the study. The drug was carefully applied and spread on the forehead of the volunteer. Standard procedures of preapplication skin stripping and for occlusion of the applied product were followed. Plasma samples withdrawn through 10 hours post-dose [including a zero time sample] were assayed for diclofenac by an HPLC technique. Tmax in the three products were 4 hours. Cmax and AUC were significantly lower for the test products indicating their bioinequivalency. Quantitative pharmacokinetic differences among the three products were obtained. Advantages of the utilized model for evaluating the in vivo availability of diclofenac emulgel were discussed

Influence of protein malnutrition on susceptibility to induction of cleft palate by cortisone in mice 1,2

The objective of the present work is to evaluate the possible influence of protein malnutrition on drug teratogenicity by utilizing the well established experimental model for cleft palate induction by cortisone in mice. The study was performed on 150 female pregnant albino Swiss mice. Animals were fed throughout pregnancy either by balanced normal diet [20% casein] or by low protein diet [5% casein]. Hydrocortisone acetate was administered intramuscularly in the dose levels of 2.5 and 5.0 mg daily from the 11th to the 14th day of gestation [vaginal plug marks day 1]. The outcome of pregnancy was examined at day 18th for implantations, resorptions, viability of fetuses, fetal body weights and external anomalies. The fetal palates were examined histologically. The obtained results showed that protein malnutrition increases the incidence of resorptions and decreases the fetal body weights. These effects were potentiated following cortisone treatment. The state of protein malnutrition did not induce cleft palates, but it increased the incidence of cleft palates from 77.5 to 97.0% and from 84.4 to 100% following the administration of 2.5 and 5.0 mg/kg of hydrocortisone, respectively. Thus, protein malnutrition potentiates the teratogenecity of cortisone in mice. The possible mechanisms for this action are discussed

simple integrated battery of tests for assessing the behavioral effects of drugs in rats

A program is under construction at present time in NODCAR for building up a neurobehavioral check-list of experiments, which can be easily and integratedly used in toxicological evaluations of drugs and chemicals. The present work is a part of this program. Its objective has been to evaluate the use of the open field test, the swimming test and the conditioned avoidance and escape behavior testing as an integrated battery for assessing the behavioral effects of drugs. The used animals were Sprague-Dawley rats. Two reference behaviorally action drugs were utilized, Chlorpromazine [1.5 and 3.0 mg/kg i.p.] and Amphetamine [1.0 and 2.0 mg/kg i.p.]. The evaluated parameters were latency, ambulation, rearing and grooming in the open field, swimming latency, swimming time direction in the swimming test, in addition to the avoidance behavior. The above mentioned methodologies were able to demonstrate the dose-dependent potential interference of Chlorpromazine and Amphetamine with emotionality, memory learning, motor activity and muscular coordination

Influence of protein malnutrition on behavioral response to drugs in rats

The aim of the present work was to study the effect of PM on susceptibility of rats to the behavioral response of drugs. Chlorpromazine [CPZ] and Amphetamine [AMP] were utilized as reference drugs. PM was started from birth. The performed tests were the swimming test, the open-field test and the test for escape and conditioned avoidance response. They were performed when rats were in the ages of 50-60 days, 92-102 days, and 134-144 days, respectively. Chlorpromazine [1.5 and 3.0 mg/kg] and Amphetamine [1 and 2 mg/kg] were given intraperitoneally. The obtained results showed that PM and normally fed [NF] animals behave differently. PM decreased the swimming latency time but did not affect the swimming time or direction. It decreased the latency time and increased the ambulation frequency in the open-field tests. In the escape and conditioned avoidance experiments, no effects were produced by PM, however, the number of trials for learning were significantly higher in PM animals. On administering CPZ or AMP, the obtained neurobehavioral responses in protein malnourished animals were similar to those obtained in NF animals with the following exceptions: Longer swimming latency time after CPZ and shorter one after AMP, shorter swimming time following low dose of CPZ and AMP, higher degree of ambulation following the high dose of CPZ, shorter exploration latency time following low dose of AMP [Open Field], lower degree of interference with avoidance response following CPZ administration. The obtained results will be discussed in view of the neurobehavioral properties of PM, CPZ and AMP

Effect of caffeine on sulfamethazine N-acetylation and urinary excretion in healthy volunteers

The aim of the present work has been to study the influence of caffeine on the gastrointestinal absorption as well as the elimination of sulfamethazine following their concomitant oral administration in man. Five healthy volunteers [2 males and 3 females] participated in the study. Sulfamethazine was orally given in the does of 1 g either alone or preceded by 100 mg caffeine. Urinary excreted amounts of sulfamethazine and N-acetylsulfamethazine were determined at different time intervals during at least 36 hours. The following pharmacokinetic parameters were computed for sulfamethazine and its N- acetyl derivative in each individual: Cumulative amount excreted, urinary excretion rate, Cmax, Tmax, rate constant of elimination and AUC. The obtained data showed that the effect of caffeine on the gastrointestinal absorption of sulfamethazine is individual-dependent. Significant decrease in absorption occurred in 3 volunteers. The extent of N-acetylation was not affected. The obtained findings are discussed in view of the pharmacodynamics of caffeine as well as the possible pharmacotherapeutic consequences

Cytotoxicity of caffeine

Toxicity of caffeine was studied in vitro on two types of cells using the cell culture technique. The evaluated parameters were cell detachment and cell growth. Five concentrations of caffeine in the range of 2x10-6 to 2x10-2 M were tested. Similar patterns of cytotoxicity were observed on the used types of cells. Results were evaluated in comparison with the toxic potential of other chemical agents. According to the obtained results, caffeine may be classified as a substance of mild cell toxicity potential

effect of calcium on acute toxicity of verapamil

In previous studies, we showed the beneficial effect of calcium [Ca] in reversing the undesirable toxic effects of verapamil [V]. The aim of this study is to clarify the effect of Ca on the acute toxicity of V. The intraperitoneal [I.P.] LD[50] of V was estimated in mice. Re-estimation of the LD[50]of V was carried out in presence of 1/4 the LD[50] of Ca. In addition the LD[50]of Ca, was estimated in mice, followed by re-estimation in presence of 1/4 the LD[50]of V. The results revealed that the presence of Ca inhibits the acute toxicity of V and vice versa