Department of Pharmacology, Faculty of Veterinary Medicine, Benha University, 13736 Moshtohor

Background: To shed some light on full characterization and utilization of non-steroidal anti-inflammatory drugs (NSAIDs) in veterinary medicine, this study, therefore, was designed to clarify the pharmacological effects of two NSAIDs (one selective, that is meloxicam, and the other is non-selective, that is piroxicam) on intestinal contractility of rabbit as a farm animal species.Methods: Rabbits were humanely slaughtered, and segments from different parts of intestinal tracts were dissected out and an intestinal segment of about 2 cm long was fixed in an organ bath containing warm oxygenated Tyrode’s solution at 37°C. The tissue was subjected to a resting tension of 2 g and allowed to equilibrate for 30 min and then the effects of graded increased concentrations of piroxicam and meloxicam were demonstrated on the normal rhythmic motility of the isolated intestinal segments. The sites of action of piroxicam and meloxicam were tried.Results: Piroxicam and meloxicam exhibited concentration-dependent relaxations of intestinal smooth muscle segments with minimal and maximal effects of more potency by prioxicam than meloxicam. Calculated inhibitory concentration 50% were 15.45 and 23.10 μg/ml bath for piroxicam and meloxicam, respectively. Effects of either piroxicam or meloxicam did not involve cholinergic, adrenergic, histaminergic, nitrergic, or purinergic pathways as the application of the corresponding agonists/antagonists did not affect the inhibitory response of piroxicam and meloxicam. It was assumed that the effects of the drugs were attributed to the direct effects of the drugs on the intestines in addition to inhibiting endogenous prostaglandin synthesis activity via their cyclo-oxygenase inhibiting properties.Conclusions: Data of the present study may indicate that piroxicam and meloxicam could be used effectively and safely in rabbits for their anti-inflammatory actions in small therapeutic doses. However, in large doses, they (particularly, piroxicam) may produce depressant effects on gastrointestinal tract motility that should be taken in consideration in the case of introducing these drugs in therapy with larger doses

Anti-inflammatory potential of Agaricus in carrageenan-induced model of local inflammation in rats

Background: The concept of effects of Agaricus on inflammatory responses is still controversial. This study, therefore, was designed to assess the potential of the anti-inflammatory effect of Agaricus 100% extract on acute inflammation using the model of carrageenan-induced paw edema in rats.Methods: Four groups among five (six rats each) have been injected with carrageenan (0.1 mL of 3% solution), intra-plantar in the right hind paw; the first group was injected with saline instead in the same manner and kept as control. An hour earlier, rats received different treatments, either saline (inflamed control), or diclofenac (inflamed, standard-treated), or Agaricus extract (5 mL/kg as small dose or 10 mL/kg as a large dose). The volume of the developed paw edema has been measured at an hour interval fashion (1~6 hrs) and at 24 hrs.Results: Agaricus extract showed inhibitory effects on the carrageenan-induced edema in time- and dose-dependent manner, at the late phase (2~ hrs) of the inflammatory response (small dose) and at both early (~2 hrs) and late phases (large dose). The effects were comparable to those of diclofenac being 11.74, 08.46, 08.99, 09.72 and 09.89% at 2-6 hrs (small dose); 14.04, 23.91, 21.92, 17.99, 15.63 and 16.96% at 1-6 hrs (large dose); 16.85, 31.30, 35.38, 35.97, 34.72 and 34.63% (diclofenac). The anti-inflammatory effect of Agaricus could be attributed to its phytochemical content which may inhibit the inducible inflammatory mediators (as prostaglandins and nitric oxide) in the late phase (small dose) and/or inhibiting both early (histamine and oxygen free radicals) and late mediators (large dose).Conclusions: These data may indicate that Agaricus extract has the potential of anti-inflammatory activity that could be applied in acute inflammatory disorders

SYNTHESIS OF NEW PYRIMIDINE DERIVATIVES AND EVALUATION OF THEIR ANTICANCER AND ANTIMICROBIAL ACTIVITIES

ABSTRACTObjectives: The objective of this work is to synthesize new pyrimidine derivatives starting from ethyl 2,4-dioxo-4-(thiophen-2-yl)butanoate.Several oxadiazole, triazole, and thiadiazole moieties were incorporated into the pyrimidine backbone. The structure of the novel compounds wascharacterized by elemental analysis and spectroscopic methods.Methods: Synthesis of the target compounds was materialized starting from 2-oxo-6-(thiophen-2-yl)-2,3-dihydropyrimidine-4-carbohydrazide (4)which was prepared from the appropriate ethyl 2-oxo-6-(thiophen-2-yl)-2,3 dihydropyrimidine-4-carboxylate (2). Several synthetic pathways wereused for the preparation of the targets. Some of the newly synthesized compounds were subjected to in vitro cytotoxic screening against breastcarcinoma and colon carcinoma cell lines. On the other hand, the antimicrobial activity evaluation of some newly prepared compounds was performedusing cup plate diffusion method.Results: It was observed that the oxadiazole derivative 7b was the most potent compound against breast carcinoma cell line (IC=7.6 μg/ml). However,pyrimidine carrying substituted 1,2,4-triazole-2-thione moiety at position 6, 11 showed the highest cytotoxic activity against colon carcinoma cellline (IC50=4.7 μg/ml). On the other hand, compound 5c was the most active broad spectrum antimicrobial agent against the chosen microbial strains.Conclusion: From the observed results, further investigations recommended for the synthesis of heterocycles incorporated to pyrimidine backboneas cytotoxic as well as broad spectrum antimicrobial agents.Keywords: Pyrimidine, Oxadiazole, Triazole, Thiadiazole, In vitro anticancer study, Antimicrobial study.5

Lipid profile improving effect of Coriandrum sativum seed extract in rats

Background: Hyperlipidaemia is a common disease in middle-aged and elderly people. It has received attention, as it indirectly affects the normal metabolism, blood viscosity and vital organ functions. It is a risk factor for cardiovascular and cerebrovascular diseases. Therefore, the aim of the present study was to evaluate the possible antihyperlipidemic effect of Coriander sativum seed extract (CSSE) in rats fed on high-fat diet.Methods: A parallel study design was adopted on 42 albino rats, divided randomly into 7 groups with different treatments. After a 6 week-experimental course, blood samples were collected and analysed for lipid and organ function parameters. Phytochemical analysis was conducted on the used seed extract to detect the active principles underlying its effects.Results: CSSE (150 and 300 mg/kg, orally, once daily) along with a high-fat (1.5% cholesterol+1.5% coconut oil, in diet) diet resulted in a significant (p≤0.05) improvement in plasma lipid parameters, including, total cholesterol, triacyglycerols and lipoproteins, compared to the high-fat group. group. The extract significantly (p≤0.05) improved hepatic (total proteins, albumin, globulins, total conjugated and unconjugated bilirubins, AST, ALT, GGT), cardiac (CK-MB and troponin-I) and renal (urea, creatinine & uric acid) biomarkers. Phytoanalysis of CSSE revealed presence of phlobatannin and flavonoids. The protection % produced by small and large doses of CSSE were dose-dependent and parallel to those of the standard antihyperlipidemic rosuvastatin (2 mg/dl orally, daily).Conclusions: These data indicate that CSSE has a marked antihyperlipidemic effect and could be a source for a promising nutraceutical antihyperlipidemic drug depending on its high phenolic and flavonoid content

Ciprofloxacin and levofloxacin adversely affect male infertility indicated by pharmacological, andrological and pathological evidence

Background: Drug-induced reproductive organs toxicities is an important aetiology in investigation of male infertility. The aim is to study levofloxacin effect on male reproductive system in comparison to ciprofloxacin.Methods: Twenty-five male wister rats weighted 230±20 gm and aged 8 weeks were randomly divided into five groups of five. The first group received ciprofloxacin with dose 78.23 mg/kg/day in 2 doses (therapeutic dose). The second group received the double dose of the first group ciprofloxacin. The third group received levofloxacin with dose 39.11 mg/kg/day once daily (OD) (therapeutic dose). The Fourth group received the double dose of the third group levofloxacin. However, the fifth group served as a control and received normal saline with carboxymethylcellulose OD. All treatments were administered orally for 14 days. On the 15th day, blood samples and reproductive organs were obtained from all rats. Testicular tissues were prepared for genetic testing and chemical and microscopical examination.Results: Ciprofloxacin and levofloxacin negatively altered reproductive organ weights, sperm parameters and serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) level (p<0.05). Additionally, serum testosterone level was significantly deceased in ciprofloxacin-treated group (the double dose) (p<0.05) relative to control. The difference between ciprofloxacin and levofloxacin was significant in seminal vesicle weight and serum LH and FSH level (p<0.05). Testicular histopathological changes were also found with the two drugs with different degrees. Effects of levofloxacin and ciprofloxacin were dose-dependent.Conclusions: Both ciprofloxacin and levofloxacin adversely affect andrological function that should be monitored and controlled during application of these drugs

Gentamicin and amikacin adversely affect male infertility indicated by pharmacological, andrological and pathological evidence

Background: Many drugs are implicated in male infertility and screening for medication history is an important for diagnosis and treatment of the problem. The aim is to study amikacin effect on male reproductive system in comparison to gentamicin.Methods: Twenty-five male wister rats weighted 220±20 gm and aged 8 weeks were randomly divided into five groups of five. The first group received gentamicin in dose 18.25 mg/kg/day once daily (OD) (therapeutic dose). The second group received gentamicin with double dose of the first group. The third group received amikacin in dose 54.75 mg/kg/day OD (therapeutic dose). The Fourth group received amikacin with double dose of the third group. However, the fifth group served as a control and received normal saline (NS) OD. All treatments were administered intraperitoneally (IP) for 14 days. On the 15th day, blood samples and reproductive organs were obtained from all animals. Testicular tissues were prepared for genetic testing and chemical and microscopical examination.Results: Amikacin and gentamicin negatively affected reproductive organs weights, sperm parameters, serum follicle stimulating hormone and luteinizing hormone (LH) level relative to control (p<0.05). However, serum testosterone level was only affected with gentamicin (p<0.05). A significant difference between gentamicin and amikacin was found in sperm count, testis and epididymis weights and serum testosterone and LH level (p<0.05). Testicular histopathological changes were also found with the two drugs with different degrees. Effects of both gentamicin and amikacin were dose-dependent.Conclusions: Both gentamicin and amikacin adversely affect andrological function that should be monitored and controlled during application of these drugs

Laboratory evidence for the hematopoietic potential of Beta vulgaris leaf and stalk extract in a phenylhydrazine model of anemia

This study was designed to provide laboratory evidence supporting the hematopoietic effect of Beta vulgaris (beet) leaf aqueous extract in phenylhydrazine-induced anemia model in albino rats. Extraction of the leaves/stalks was done by maceration in 30% hydro-ethanol for 48 h. An intraperitoneal injection of 20 mg/kg phenylhydrazine was applied for two consecutive days to develop hemolytic anemia on the 4th day after the 1st injection in 24 of 30 male albino rats. The animals were divided into 5 groups and received the following treatments: standard (ferrous ascorbate + folic acid; 13.5 + 0.135 mg/kg), B. vulgaris extract (100 and 200 mg/kg), or left untreated (normal and diseased controls). Blood samples were taken at 0, 4, 8, and 12 days of the experiment for hematological and clinico-chemical analysis. Beet leaf extract significantly restored the levels of red blood cells, white blood cells, hemoglobin, and hematocrit in dose- and time-dependent manners. Blood indices have been significantly corrected. Erythropoietin level was maintained at higher levels. Erythrocytic membrane oxidation biomarker (malondialdehyde) level was significantly reduced compared to the anemic untreated group. The extract exhibited potent, concentration (4–512 μg/mL)-dependent antioxidant activity indicated by the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay, with IC50 value of 37.91 μg/mL. Beet leaf extract resulted in detection of flavonoid and phenolic compounds that may underlie its hematinic properties. These findings may indicate B. vulgaris as a good natural source for pharmaceutical preparations with hematopoietic effects and treatment of anemia and/or associated conditions

Effect of Intramuscular Injection of Tobramycin on Some Biochemical Parameters in Blood of Sheep

Abstract: The object of the present study was to assess the possible alterations in blood of sheep that may occur following intramuscular injection of tobramycin. Tobramycin was injected to 10 sheep at a dosage regimen of 5 mg/kg of body weight for 5 successive days. Two types of blood samples (with and without EDTA as an anticoagulant) were collected from the jugular vein before and after the antibiotic course. Tobramycin significantly (p&lt;0.05) increased levels of blood urea nitrogen, creatinine, aspartate aminotransferase, alkaline phosphatase, sodium and calcium. On the other hand, it significantly (p&lt;0.05) decreased serum total bilirubin level. Other parameters including, erythrocytic count, packed cell volume, hemoglobin, total and differential leukocytic counts, alanine aminotransferase, G-glutamyltransferse, potassium and phosphorus did not show any significant difference when compared with those of prior-administration samples. These data suggest that tobramycin should be used with care in treatment of sheep with renal impairment; its dosage regimen should be adjusted to avoid its nephrotoxic effect

Modulation of acute phase parameters of inflammation by probiotics in albino rats

We investigated the effect of the probiotic Lactobacillus acidophilus on acute phase parameters in infected animals and to evaluate its possible use as alternative to replace the classical anti-inflammatory drugs as a trial to avoid the side effect of these drugs and its disadvantages. Forty albino rats were divided into four groups, group A was given saline orally and kept as normal-control rats, group B was orally given Lactobacillus acidophilus at a dose regimen of 10 8 CFU/day and kept as normal-treated rats for 6 weeks, group C was experimentally infected with Salmonella typhimurium (0.2 mL of 1.5 × 10 8 CFU/mL) and received saline orally to be kept as diseased-control rats, while group D was orally given Lactobacillus acidophilus (10 8 CFU/day) for 6 weeks and experimentally infected with Salmonella typhimurium and kept as diseased-treated rats. Results of group D revealed significant decrease in ESR, fibrinogen, TIBC, UIBC, and ceruloplasmin, especially on the 34th day post infection. On the other hand, significant increase in total proteins, albumin, total iron, and transferrin saturation percentage was revealed, when compared with group C. These data indicate that the probiotic Lactobacillus acidophilus may alter acute phase proteins after infection and significantly reduce the degree of inflammation