Role of the trace metals, selenium and zinc, in pilocarpine-induced epilepsy in rats

Excitotoxic brain lesions, such as epilepsy, lead to increasing destruction of neurons, in the course of few hours after the insult. The deadly cascade of events possibly involves detrimental actions by free radicals, proinflammatory cytokines and the activation of pro-apoptotic transcription factors, which finally result in neuronal destruction. Several reports suggest that the level of some trace elements play a vital role in seizure conditions to prevail. The aim of the present study was to assess the possible modulatory role of the trace elements, selenium and zinc on pilocarpine-induced epilepsy in rats.The study was carried out on 40 male albino rats, weighing 150-200 grams that were divided into the following groups each of 10 rats: Group I: control rats that received intraperitoneal [i.p.] saline, Group II: pilocarpine induced epilepsy, Group 111: selenium pretreated for 3 weeks before pilocarpine injection and Group IV: zinc pretreated for 3 weeks before pilocarpine injection. The seizure latency and severity for each rat was recorded. Twenty four hours following pilocarpine injection, rats were exsanguinated and the following parameters were determined: cerebral caspase-3 activity [as a marker of apoptosis], interleukin-lbeta [IL-ljB], reduced glutathione [GSH] and malondialdehyde [MDA] concentrations, serum neuron specific enolase[NSE] concentration [as a marker of brain injury].Intraperitoneal injection of pilocarpine in rats resulted in progression to limbic seizures with progressing behavioural scores at various time intervals [recorded every 30 minutes up to 2 hours]. Latency to forelimb clonus was 51.86 +/- 1.89 min. The results of the present study demonstrated significantly increased cerebral MDA concentration together with significant decrease in cerebral GSH concentration in non-treated pilocarpine injected rats compared to normal control rats. A significant increase in cerebral caspase-3 activity, and in cerebral 1L-1/beta as well as in serum NSE concentrations could be observed in non-treated pilocarpine-injected rats compared to normal control rats. Pretreatment with selenium or zinc reduced the severity of pilocarpine- induced seizures. In addition, both trace elements decreased the latency to attain the forelimb clonus [score 4]. A significant decrease in cerebral MDA and IL-1/beta, serum NSE concentrations could be observed in selenium and zinc-treated rats compared to non-treated pilocarpine-injected rats. A significant' increase in cerebral GSH concentration was observed in zinc-treated, but not in selenium-treated ones.The results of the present study confirm the role of the trace elements, selenium and zinc, in mitigating epilepsy. Further human studies to evaluate the role of trace elements in epilepsy are recommended. Furthermore, since antiepileptic drugs [AEDs] are reported to induce zinc and selenium deficiency,thus combining these trace elements with AEDs are worthy to be evaluated

Role of rosiglitazone and pravastalin in freund's adjuvant arthritis and mixed-type hypersensitivity in rats

Recent studies have shown that peroxisome proliferator- activated receptor- gamma [PPAR gamma] may participate in control of inflammation, especially in modulating the production of inflammatory mediators. Similarly, the cholesterol lowering drugs, statins, have been found to exhibit anti-inflammatory properties that are beyond their lipid lowering effects. The present study was conducted to investigate the effect of a PPAR gamma agonist [rosiglitazone] and a statin [pravastatin] on immunologically mediated chronic inflammation. Two models were chosen, namely, Freund's adjuvant arthritis [FA] and mixed- type hypersensitivity [MH] in rats. The effect of these drugs was assessed on the basis of biochemical markers in blood and / or inflammatory exudate. The investigated drugs were given orally daily during the course of inflammation development. The results of the present study demonstrated that, in either model, rosiglitazone and pravastatin reduced the elevated serum and exudate [local] leukotriene B[4] [LTB[4]] and interleukine-6 [IL-6] levels. The anti-inflammatory effect of these drugs was also accompanied by reduction or normalization of elevated systemic and or local levels of lipid peroxide [LP], superoxide dismutase [SOD], and reduced glutathione [GSH]. It could be concluded that long-term treatment with rosiglitazone or pravastatin confers a good anti-inflammatory activity against arthritis in rat, leading to improvement of the oxidative stress induced by the arthritic insult. The reparative effect of these drugs could be mediated via reduction of LTB[4] and IL-6

comparative study between gliclazide, glibenclamide and glipizide on plasma glucose, C-peptide, lipid profile and on some peroxidative changes in diabetic rats

This study was performed on 50 male adult albino rats [10 normal and 40 alloxan-induced diabetic rats] divided into five groups, each of ten rats. The study recommended the use of gliclazide in NIDDM due to its excellent glycemic control and prevention of the long- term vascular complications; it also restores the abnormalities in lipid peroxides, oxidative markers and antioxidant enzymes

possible role for tamoxifen in the prevention of streptozotoain induced diabetes and its cardiovascular complications in rats

In this work the potential beneficial effects of nicotinamide, amino- guanidine, desferrioxamine and Tamoxifen in the prevention of streptozotocin induced diabetes and its vascular complications in rats were investigated. In the prophylaxis trial, nicotinamide, amino- guanidine, desferrioxamine and Tamoxifen all prevented or decreased the abnormalities in serum glucose, lipid profile, antioxidants enzymes and lipid peroxides observed in diabetic rats. Treatment of streptozotocin induced-diabetic rats by insulin corrected the observed abnormalities in serum glucose and lipid profile, still the changes in antioxidant enzymes and lipid peroxides were insignificant. Treatment of diabetic rats by insulin together with nicotinamide, amino- guanidine, desferrioxamine or Tamoxifen corrected the abnormalities in all these parameters as compared with the appropriate control groups

Effect of verapamil on theophylline kinetics and dynamics in patients with chronic obstructive pulmonary disease [COPD]

A randomized, open study was carried out to investigate the possible effect of Short-term therapy [two weeks] with the calcium channel blocker verapamil [80 mg 8 hourly orally] on the pharmacokinetics and pharmacodynamics of a single intravenous bolus dose of 5 f mg/kg theophylline ethylenediamine [aminophylline] in chronic obstructive pulmonary disease [COPD] patients. Verapamil caused a significant reduction of theophylline clearance [20.8%], the apparent volume of distribution [Vd] was slightly reduced [3.3%] whereas the volume of the central compartment [Vc] was insignificantly changed. The area under the curve [AUC] significantly increased [30%]. The terminal half life [tt/2 beta] of theophylline significantly increased [19.4%]. Although verapamil had a significant effect on theophylline pharmacokinetics in COPD patients, it did not significantly affect theophylline pharmacodynamics, particularly it did not disturb the linear relationship between serum theophylline level and its bronchodilator effect

Comparative study between the effects of digitoxin versus digoxin on ferrokinetics

Nineteen male rabbits were included in the present study and classified into three groups to study the effect of repeated oral daily administration of digitoxin [10 mug/kg body wt.] or digoxin [50 mug/kg body wt.] for four weeks on some liver functions [SGPT, SGOT, total serum bilirubin, total serum proteins, serum alkaline phosphatase and prothrombin activity], ferrokinetic parameters [basal plasma iron, post absorption plasma iron tolerance curve, TIBC, UIBC and percent saturation of transferrin], hematological parameters [red cell count, hemoglobin concentration, hematocrit value and red cell indices] and histochemical parameters [iron contents and peroxidase enzyme activity in both the liver and kidney]. The results showed that digoxin produced significant decrease of basal plasma iron, post absorption curve and percentage of saturation of transferrin with significant increase of UIBC. Digoxin produced also mild reduction of iron contents and peroxidase enzyme activity in both the liver and kidney. Digitoxin produced insignificant changes in all the studied parameters. The findings of the present study may suggest that oral administration of digoxin interferes with some ferrokinetics, mainly the intestinal absorption of iron. The effect of digoxin on ferrokinetics seems to affect the cellular iron containing enzymes. The addition of iron therapy was recommended, whenever possible, to patients receiving digoxin for a long time

Propranolol withdrawal and thyroid function in the rabbit

Propranolol without manifestations is now known to have strong correlation to thyroid hormones. Conflicting results are reported by different workers regarding the influence of sudden propranolol withdrawal on the different parameters related to thyroid functions. The present study was conducted on adult male rabbits to explore the effect of propranolol administration [30 mg/kg/day orally] for four weeks and its subsequent withdrawal on the pituitary thyroidaxis; namely, serum TSH, total T4, free T4, total T3 and free T3. The withdrawal period ranged from one day and extended up to 12 days. Total serum T3 was found to be significantly reduced following the prolonged daily oral administration of propranolol, while propranolol withdrawal led to a significant elevation of serum free T3 as compared with three and six days following drug cessation. These results emphasized the importance of free T3 in the production of propranolol withdrawal manifestations, while the nonsignificant changes of serum total T3 on propranolol withdrawal may be due to changes in serum protein binding capacity affecting total T3 but not free T3

Possible alteration of some cardiovascular and hormonal parameters after abrupt withdrawal of propranolol or guanfacine following chronic mono-or combined therapy in spontaneous hypertensive rats

Spontaneous hypertensive rats [SHR] were given either propranolol [P], guanfacine [G] or combined treatment for four weeks, followed by sudden withdrawal of either [P] or [G] for 6 days. Results showed a significant decrease of the systolic blood pressure, heart rate and plasma renin activity after [P], [G] or combined treatment with a significant rebound increase after withdrawal. Concerning plasma aldosterone concentration, a significant decrease of this parameter was detected only after [G] treatment with a rebound significant increase after withdrawal. As regards angiotensin converting enzyme activity, there was a significant decrease of this parameter after [P] treatment with a significant rebound increase after withdrawal. Total daily urinary catecholamine exhibited a significant increase after [P] treatment and even after its withdrawal but there was a significant decrease after propranolol withdrawal in the group treated with both drugs. There was also a significant decrease of this parameter after [G] or combined treatment with a rebound significant increase after withdrawal of [G]. A significant increase of serum potassium was apparent after [P] or combined treatment with a significant decrease after withdrawal. These results indicated that propranolol and guanfacine are effective antihypertensive agents, besides, when a drug is to be withdrawn from the combination regimen, it is the beta- blocker rather than guanfacine

Effect of calcium antagonists on platelet aggregation and screening tests of blood coagulation

Platelet hyperfunction has been described in patients with coronary heart disease, which has stimulated the use of platelet-suppressive drugs in order to alter the course of patients with coronary heart disease. Calcium plays an important role in platelet aggregation and release reactions. Thus calcium channel blockers might be expected to inhibit platelet aggregation in response to vascular injury. Nifedipine [Adalat] and Veropamil [Isoptin] were injected in male rabbits and their effects were studied against a control group of 10 male rabbits. Results prefer the use of drugs exerting a selective platelet inhibitory action with calcium antagonist in the prevention and treatment of coronary artery disease

Phenytoin-oxamniquine interactions

Forty adult male rabbits were divided into four groups: Control group, phenytoin [DPH] group, oxamniquine group and a combined group. Fasting blood samples were collected one hour after the last dose using the orbital technique of Riley. Estimation of serum free fatty acids [FFA], total cholesterol, triglycerides, and DPH are done. It was found that combined use of DPH and oxamniquine resulted in a significant increase of serum FFA, total cholesterol and triglyceride, while a nonsignificant increase was noticed in the phenytoin [DPH] group

Study of the influence of the antihistaminic mepyramine maleate on the epinephrine induced lipolysis in the rabbit

This study were conducted on 34 male rabbits which were divided into 4 groups: Epinephrine group [6], mepyramine group [8], combined group [10], and a control group [10]. Fasting blood sugars were collected 20 minutes after epinephrine administration, 30 minutes after mepyramine administration to study the acute effects, other blood samples were collected after 7, 14, 21 days to study the effects of prolonged use by measuring the free fatty acids level, cholesterol, and triglycerides levels. It was found that mepyramine maleate induced a significant increase of plasma FFA with no change on cholesterol nor triglyceride levels. Prolonged use led to increasing both FFA, and cholesterol levels

Effect of Ca++ chaxrnel blocking agents on experimental hyperthyroidi in the dog

This work was designed to study the effect of Ca++ channel blockers [verapamil and nifedipine] on hormonal release and actions in hyperthyroidistn. In hyperthyroid crisis, intravenous verapamil decreased serum tniodothyronine [T[3]], blood pressure, heart rate and double product cardiac output index and succeeded to reduce the encountered supraventnicular and ventricular arrhythmias. Nifedipine decreased the blood pressure and double product index, yet it did not induce any significant effect on thyroid honones or blood lipids. In chronic hyperthyroidiam, verapamil increased serum lipids and controlled nearly all cardiovascular complications of the disease. Nifedipine increased both serum triiodothyronine and tetraiodothyronine [Thyroxine, T[4]], as yell as free fatty acids [FFA]. It controlled hyperthyroid hypertension, but failed to control the rest of the existing cardiovascular ccniplications

Effects of Ca++ channel blocking agents on pituitary thyroid hormones, serum lipids and cardiovascular functions in euthyroid dogs

The effect of verapamil and mifedipine was studied in euthyroid dogs to detect whether these drugs alter pituitary-thyroid output and/or actions. Verapamil induced a significant decrease of serum TSH, T[3] and T[4] as well as significant increase of serum lipids. It also exhibited a bradycardiac action. Nifedipine decreased only serum T[3] and induced a significant increase in serum FFA and total cholesterol. It also led to a decrease in diastolic pressure and an increase in heart rate

Effect of oral ascorbic acid on blood lipids corticosterone, aldosterone and angiotensin II

Big oral doses of ascorbic acid [500 mg/Kg. daily] given to male rabbits fed an atherogenic diet led to a significant decrease of blood lipids namely total serum cholesterol, triglycerides, free fatty acids [FFA] and plasma phospholipids after 30 and/or 90 days as compared to animals fed an atherogenic diet alone without ascorbic acid. Administration of ascorbic acid for 90 days in the same dosage to animals receiving a normal diet resulted in an increase of plasma aldosterone, corticosterone and angiotensin II; yet only corticosterone changed significantly. Liver function tests namely serum glutamic pyruvic transaminase [SGPT] and thymol turbidity did not exhibit any significant changes as compared to the control group. No electrocardiographic changes were noted in any of the animals receiving vitamin C. These results were fully discussed

Effect of experimental chronic exposure to tobacco smoke on the plasma level of some suprarenal cortical hormones, angiotensin II, serum sodium and potassium

Twice daily exposure of male rabbits to tobacco smoke inhalation under controlled test conditions led to significant increase of plasma aldosterone as well as angiotensin II. On the other hand, plasma corticosterone and both serum sodium and potassium were not significantly affected. These results were discussed

Effect of chronic exposure of rabbits to hashish smoke on some hematological aspects, blood lipids and lipoprotein lipase activity

The effect of chronic exposure of rabbits to hashish smoke every other day for 30 days, was investigated on blood count, plasma lipids and lipoprotein lipase activity. The red cell count as well as the haemoglobin content decreased significantly. The total leucocytic count was not altered, yet the differential count showed a significant rise of polymorphs, together with a significant decrease of lymphocytes. Regarding lipids, the plasma free fatty acids [FFA] and lipoprotein lipase activity decreased significantly, while the total plasma cholesterol and triglycerides did not change. These results were discussed

Modification of the possible influence of some environmental factors on blood coagulation and fibrinolysis by angiotensin II and neomercazole

Adult male rabbits were exposed to 45 C for 30 minutes, 4 C for 15 minutes, 5% carbon dioxide [CO[2]] in air for 30 minutes, 100% oxygen [O[2]] for 30 minutes, infra red lamp for 30 minutes and ultra violet light with a principle wavelength of 3, 650 A for 30 minutes. These environmental factors did not result in any significant alterations of whole blood clotting time, one stage prothrombin time, kaolin cephalin clotting time, fibrinogen level as well as platelet aggregation. Blood fibrinolytic activity [F.A.] showed marked enhancement following heat, excess CO[2] and infra red light exposures, while the rest of the physiological stresses did not lead to any significant changes of this parameter. The possible role of vasodilatation and/or thyroid gland in mediating the observed changes of fibrinolysis was investigated through the use of angiotensin and neomercazole. These experiments confirmed the role of vasodilatation but not the thyroid. These results were discussed