Effect of escitalopram and venlafaxine on seizure score and lipid peroxidation in mice receiving carbamazepine antiepileptic therapy

The frequent co-existence of depression in epileptic patients raises the issue of simultaneous use of antidepressants along with anti-epileptic drugs in management of such cases. However, it is necessary to evaluate the safety of these antiepileptic/antidepressant drug combinations. The present study investigates the effect of either antidepressant; escitalopram [selective serotonin reuptake inhibitor, SSRI] or venlafaxine [serotonin/noradrenaline reuptake inhibitor, SNRI], administered alone or in combination, with the conventional antiepileptic drug carbamazepine on chemo-convulsions induced by picrotoxin. In addition, the effect of both antidepressants on lipid peroxidation, as an assumable cause of neuro-degenration in epilepsy, was studied in a model of chronic restraint in mice. The results show enhancement of seizure severity with significant increase in lipid peroxidation upon escitalopram treatment whether alone or in combination with carbamzepine. On the other hand, venlafaxine, administered alone or in combination with carbamazepine, provided significant protection against picrotoxin-induced convulsions as well as lipid peroxidation favoring its application in management of epilepsy-depression co-morbidities

Nicotine potentiates the antidepressant effects of imipramine and sertraline

Clinical observations suggest the involvement of nicotinic acetylcholine receptors [nAChRs] in depressive illness. There is no clear cut evidence that nicotine produces an antidepressant effect. The antidepressant effect was assessed by the forced swimming test using male albino mice. Nicotine [1.2 mg/kg s.c.] given 15 min. before the test exerted no effect on immobility. Given 30 min before the test, imipramine and sertraline [each 20 mg/kg i.p.] produced a significant decrease in immobility; coadministration of nicotine [1.2 mg/kg, 15 min before the test] to either imipramine or sertraline-treated mice resulted in an enhancement in anti-immobility effect. The study further investigated the effect of nicotine, alone and in combination with either imipramine or sertraline on sucrose consumption in mice exposed to 3-weeks application of stressors. There was a reversal of anhedonia 3 weeks after i.p. administration of the antidepressant drugs given alone, and this reversal was enhanced when nicotine was co-administered with them

Effect of paroxetine and venlafaxine on mice exposed to chronic mild stress

The role of gamma-amino butyric acid [GABA] in mood disorders and its interaction with serotonin [5-HT] and norepinephrine [NE] systems is worthy of further study. Many studies reported that plasma GABA levels are relatively reduced in depressed patients. The present study investigated the alteration of GABA content by long-term antidepressant treatment with either paroxetine as one of the selective serotonin r-euptake inhibitors [SSRIs] or venlafaxine as a serotonin-norepinephrine re-uptake inhibitor [SNRI] in the frontal cortex [F.Cx] [as a brain region crucial for the control of emotion and cognition] obtained from male mice exposed to chronic mild stress[CMS]-induced anhedonia. The long term behavioral changes of the CMS without and with antidepressant treatment were also tested using the forced swimming test [FST]. The results demonstrated the reversal of CMS-induced anhedonia after 3 weeks i.p. administration of 1 and 8 mg/kg/day paroxetine and venlafaxine, respectively. Furthermore, venlafaxine seems to be more efficacious than paroxetine in long-term behavioral changes recorded by the FST. Additionally, there was a significant [p<0.001] increase in the GABA content of the F.Cx of mice exposed to CMSinduced anhedonia. The present study suggested that GABA levels may be decreased in an animal model of depression and its reversal together with the behavior improvement by either paroxetine or venlafaxine could support the hypothesis that modification in GABAergic activity in mood disorders may complement the monoaminergic and serotonergic theories, proposing that the balance between multiple neurotransmitter systems may be altered in these disorders

Simvastatin improves vascular reactivity of rabbit aorta irrespective of its hypocholesterolemic effect

Simvastatin is one of the 3-Hydroxy-3-methylglutaryl coenzyme A reductase [HMG-Co-A] inhibitors known for their hypocholesterolemic effect. Apart from cholesterol lowering, simvastatin exerts other beneficial effects such as reduction of plasma fibrinogen and platelet aggregation, anti-inflammatory, anti-proliferative effects, and decreasing risk of coronary heart disease [CHD] and myocardial infarction. This work aimed at investigating the possible modifying effect of simvastatin on systemic vascular reactivity. Vascular responses to various vasoactive agents were tested on isolated rabbit aortic ring preparations obtained at the end of 16 week duration from control normocholesterolemic [group 1], hypercholesterolemic [group 2] as well as simivastatin-treated normocholesterolemic [group 3] and simvastatin-treated hypercholesterolemic [group 4] animal groups. Hypercholesterolemia was induced in groups 2 and 4 by a high cholesterol diet for the 16 weeks. Treated groups [3 and 4] received simvastatin in a daily dose of 10 mg/kg for 8 weeks starting by the beginning of the 9[th] week. In addition to vascular reactivity studies, plasma cholesterol levels were measured for all animals at the ends of 4[th], 8[th], 12[th] and 16[th] weeks. Simvastatin pretreatment significantly reduced plasma cholesterol levels in group 4 animals in comparison to group 2, decreased contractile responses to nor epinephrine [NE] and augmented relaxation induced by acehylcholine [ACh] in nomocholesterolemic [group 3] and treated hypercholesterolemic [group 4] animals compared with control or hypercholesterolemic groups, respectively. In addition, it augmented sodium nitroprusside [SNP] induced relaxant responses in tissues obtained from group 4 compared with group 2. The vasoprotective effects observed with simivastatin therapy may be mainly attributed to improvement of vascular endothelial function not only under hypercholesterolemic- but also normocholesterolemic conditions. Thus simvastatin therapy may be applied not only to reduce the risk of CHD but also the systemic vascular complications associated with hypercholesterolemia. In addition simvastatin might serve as a prophylactic agent against disturbed vascular reactivity that may develop under certain pathological conditions devoid of hypercholesterolemia

Comparison between morning and evening single dose administration of simvastatin on endothelium-dependent relaxation and superoxide dismutase enzyme level as an antioxident marker in cholesterol-fed rabbits

Statins are widely used hypocholesterolemic drugs that act through reversible competitive inhibition of the hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase [HMGCOA] enzyme. At first, morning use of statins was recommended but now it is known that choesterogenesis follows a circadian rhythm as it occurs at a higher rate during the evening time. Accordingly, accurate timing of statin administration should be re-evaluated in order to obtain the best therapeutic effect. As simvastatin is one of the widely prescribed HMG-CoA reductase inhibitors, it was chosen in this study to test and compare its effectiveness when administered as single dose in the morning and in the evening. The experiments were performed on Newzealand rabbits divided into four equal groups, each composed of 8 animals: control normocholesterolemic, hypercholesterolemic nontreated, hypercholesterolemic treated with morning simvastatin, and hypercholesterolemic treated with evening simvastatin. Animals of control group received a cholesterol-free diet for 16 weeks, while animals of the other three groups were maintained on a high cholesterol diet for an equal duration of time. Treated groups received simvastatin in a single oral daily dose of 10 mg/kg for 8 weeks starting at the beginning of the 9[th] week, administered either in the morning or in the evening. Blood cholesterol level was checked for all animals at the end of the 4[th], 8[th], l2[th] and 16[th] weeks. At the end of the 16[th] week, the level of the anti-oxidant superoxide dismutase [SOD] enzyme was determined in erythrocyte [RBC] lysates obtained from animals of all groups. The animals were then slaughtered and vascular reactivity to acetvlcholine [ACh] was tested on ring preparations obtained from their isolated aortae [ring preparations]. Both morning and evening treatment with simvastatin significantly reduced blood cholesterol level, augmented relaxation induced by [ACh] and increased SOD level in RBCs lysates, in comparison with non-treated hypercholestero!emic group. However, results obtained with the evening dosing regimen were much more significant when compared with the morning dosing schedule. It is concluded that therapeutic efficiency of simvastatin is best obtained when the drug is administered in the evening rather than in the morning. This most likely occurs due to the circadian rhythm of cholesterol biosynthesis that tends to occur at a much greater rate during night as a result of increased availability of cholesterol precursors. This chronotherapeutic pattern of simvastatin recommends its night administration to ensure introduction of the drug at the correct timing thus achieving the best therapeutic effect

Comparison between the effect of bosentan and perindopril on diabetic angiopathy and nephropathy in streptozotocin-induced diabetic rats

Angiopathy and nephropathy are serious problems encountered in the management of diabetes, mellitus. There is accumulating literatrues describing some sort of hystological interaction between angiotensin II [ALI] and endothelins [ETs] in addition to their possible contributing roles in the pathogenesis of diabetic complications. In the present study, the angiotensin converting enzyme inhibitor [ACEI] perindopril to prevent or minimize the development of angiopathy [endothelial dysfunction] and nephropathy in a strepozotocininduced model of diabetes type I in albino rats. Animals were classified into six groups: untreated healthy non diabetic [ND] control rats, healthy [ND] rats treated with perindopril [3 mg/kg/day], healthy [ND] rats treated with bosentan [100 mg/kg/day], untreated diabetic rats, and diabetic rats treated with either perindopril or bosentan in the same doses described before. Rats were rendered diabetic by a single injection, in the tail vein, of 55 mg/kg streptozotocin [STZ] after overnight fast. Treatment with bosentan and perindopril was continued for 16 weeks during which the 24[th] urine volume, urinary albumin content, urine and plasma levels of creatinine as well as systolic blood pressure [SBP] were assessed at the end of each 4 weeks. At the end of the 16[th] week rats were sacrificed and the kidneys were removed for examination of histopathological changes, while the thoracic aortae were removed for assessment of the vasorelaxant effect of acetylcholine [Ach]. Diabetic rats developed typical functional changes manifested by hyperglycemia, polyuria, albuminuria, elevated SBP, reduced response to vasorelaxant effect of ACh in addition to histopathological changes manifested by tubular dilatation, diffuse interstitial edema and decreased density of the brush border of epithelial cells. In the healthy [ND] animals, changes obtained in the different parameters studied were insignificant between the treated and non-treated groups. In diabetic animals, however; both perindopril and bosentan significantly reduced albuminuria and lowered elevated SBP. In addition both drugs improved creatinine clearance and relaxant response to ACh to a large extent. Perindopril was more potent with regard to the hypoalbuminuric effect and the effect on creatinine clearance, while bosentan-induced improvement of vascular reactivity to ACh was more significant. Different potencies of perindopril and bosentan in affecting certain studied parameters suggests that the two drugs work either through different mechanisms or through similar pathways but to different extents. The renoprotective and antiangiopathic effects of both drugs were independent of the blood glucose level because this parameter was not significantly altered by either treatment. In conclusion, it seems that both angiotensin II and endothelins play an important role in the pathogenesis of diabetic angiopathy and nephropathy with probable interaction between the two systems to augment the production of such pathological disorders. Therefore, ACELs and ET receptor antagonists are highly recommended in the management of diabetic and ET receptor antagonists are highly recommended in the management of diabetic complications

reproductive status affects the oxytocin-mediated natriuresis in conscious male rats during dehydration

The present study was undertaken to investigate whether oxytocin is a possible mediator in these mechanisms by examining its role in dehydration-natriuresis in conscious male rats. It was concluded from this study that oxytocin may participate in natriuretic mechanisms for sodium regulation during the short periods of water deprivation and that the reproductive status do influence the renal responsiveness to oxytocin indicated by the augmentation of this response after testosterone treatment in animals with orchidectomy