The role of astrocytes in epileptic disorders.

Epilepsy affects about 1% of the population and approximately 30% of epileptic patients are resistant to current antiepileptic drugs. As a hallmark in epileptic tissue, many of the epileptic patients show changes in glia morphology and function. There are characteristic changes in different types of glia in different epilepsy models. Some of these changes such as astrogliosis are enough to provoke epileptic seizures. Astrogliosis is well known in mesial temporal lobe epilepsy (MTLE), the most common form of refractory epilepsy. A better understanding of astrocytes alterations could lead to novel and efficient pharmacological approaches for epilepsy. In this review, we present the alterations of astrocyte morphology and function and present some instances of targeting astrocytes in seizure and epilepsy.

Nigella sativa L. seed regulated eNOS, VCAM-1 and LOX-1 genes expression and improved vasoreactivity in aorta of diabetic rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Nigella sativa L. seed has been widely used in traditional medicine for the treatment of diabetes. The major reason for vascular complications in diabetic patients is endothelial dysfunction. However, the impact of N. sativa seed on endothelial dysfunction in diabetes remains unclear. AIM OF THE STUDY: This study was conducted to evaluate the effect of the hydroalcoholic extract of N. sativa seed on eNOS, VCAM-1, and LOX-1 genes expression and the vasoreactivity of aortic rings to acetylcholine (Ach) in streptozotocin (STZ)-induced diabetic rat. MATERIALS AND METHODS: Treated rats received N. sativa seed extract (100, 200, and 400 mg/kg) daily by gavage for 6 weeks. The fasting blood glucose and lipids were measured and atherogenic index of plasma (AIP) was calculated. The endothelium-dependent vasoreactivity responses of isolated aortic rings were evaluated in the presence of cumulative concentrations of Ach (10-8-10-5 M). eNOS, VCAM-1, and LOX-1 genes expression in aortic tissue was assessed by using real time polymerase chain reaction (PCR). RESULTS: Male diabetic Wistar rats treated with N. sativa seed extract for six weeks reduced serum glucose and lipids and improved AIP. The vasorelaxant responses of aortic rings to Ach were markedly improved. N. sativa seed significantly increased eNOS in mRNA expression level and function, while it decreased VCAM-1 and LOX-1 expressions in vascular cells of aortic tissue which assessed only in mRNA level. CONCLUSIONS: The results of this study showed that N. sativa seed more likely, has antidiabetic and antihyperlipidemic properties and improved vasoreactivity, endothelial dysfunction, and vascular inflammation in diabetic rats' aorta.

Salix alba attenuated oxidative stress in the heart and kidney of hypercholesterolemic rabbits.

OBJECTIVE: Oxidative stress plays a critical role in the development of hypercholesterolemia-induced complications. This study evaluated the effects of aspirin and Salix alba hydroethanolic extract on oxidative stress in the heart and kidney of hypercholesterolemic rabbits. MATERIALS AND METHODS: The antioxidant activity, as well as total phenolic and salicin content of S. alba (Sa) extract were assessed by DPPH radical scavenging activity, Folin-Ciocalteu and HPLC methods, respectively. Animals were divided into two groups of control (fed with normal chow), and HD (fed with high cholesterol diet for 6 weeks). Then, hypercholesterolemic animals allocated to the following treatment groups: CHO (received HD), Sa extract (HD plus extract 60 and 120 mg/kg), and aspirin (HD plus aspirin 120 mg/kg) and received the treatments on a daily basis for 6 weeks. MDA, GSH, and nitrite concentrations as well as the activities of SOD and CAT were evaluated in cardiac and kidney tissues. RESULTS: The scavenging activity, total phenolic content and salicin were 19.1 µg/ml (IC50), 153.75 ± 3.6 mg of gallic acid/g, and 18.03 µg/mg, respectively. In comparison to CHO group, MDA levels were diminished in Sa and ASA groups but GSH levels were improved. NO metabolites increased in the heart of Sa 120 mg/kg group and in the kidney of all Sa and ASA treated groups. SOD activity increased only in the heart of Sa groups and in the kidney of Sa and ASA groups. CAT activity increased in the heart and kidney tissues of all Sa and ASA treated groups. CONCLUSION: The results showed S. alba extract improved redox homeostasis in heart and kidney tissues of hypercholesterolemic rabbits. The extract antioxidant property may be related to its phenolic content.

Kidney stone formation and antioxidant effects of Cynodon dactylon decoction in male Wistar rats.

OBJECTIVES: The antioxidant capacity impairs in kidney and urinary bladder of animals with stone disease. Herbal medicine can improve the antioxidant condition of renal tissue. Cynodon dactylon (C. dactylon) is a medicinal plant with antioxidative and diuretic properties and different preparations of this plant have shown promising effects in stone disease. Assessment of the whole plant decoction to prevent kidney stone disease as well as its antioxidant effects was the aim of this paper. MATERIALS AND METHODS: Fifty male Wistar rats were randomly divided into 5 experimental groups (n=10). One group was left without treatment and four groups received ethylene glycol (1% v/v) in drinking water for 6 weeks. Three doses of Cynodon dactylon aqueous decoction (12.5, 50 and 200 mg/kg BW) were added to the drinking water of groups 3-5. Finally, water intake, 24-hour urine volume, MDA, total thiol concentration and FRAP value were measured in the serum and kidney tissues. The CaOx depositions were evaluated by hematoxylin and eosin staining. RESULTS: Compared to the ethylene glycol-treated group, 200 mg/kg C. dactylon, lowered stone incidents, decreased urine volume, increased FRAP/g Cr (43%) and thiol content (p<0.05) with no significant alteration of water intake, MDA decreased significantly compared to C. dactylon 12.5 (p<0.01). Kidney weight increased and body weight decreased in ethylene glycol-treated group compared to the control group (p<0.05). CONCLUSION: A minimum dose of 200 mg/kg C. dactylon reduced stone formation and simultaneously increased total antioxidant power of serum and preserved MDA content and water.

Beneficial Effects of Selective Orexin-A Receptor Antagonist in 4-aminopyridine-induced Seizures in Male Rats.

BACKGROUND: Orexins are excitatory neuropeptides which stimulate the central regulatory pathways. Orexins increase the penicillin-induced epileptic activity in rats. Orexin-A increases in different types of seizures and its elevated level is the characteristic feature in the epileptic children during polysomnography. Recently, the orexin receptor blockage has been reported to increase seizure threshold in mice; however, effect of the selective orexin-A receptor antagonist (SB-334867) on 4-aminopyridine (4-AP)-induced seizures has not been investigated. MATERIALS AND METHODS: We used the intraperitoneal injection of 4-AP to induce seizure in male rats. Under urethane anesthesia, SB-334867 (50 and 100 nmol) was injected stereotaxically into the ventral hippocampal commissure. Using video recording, the effects of SB-334867 on electroencephalogram and tonic-clonic convulsions were compared to those that received diazepam or dimethyl sulfoxide (DMSO). RESULTS: SB-334867 significantly decreased the duration of spike trains compared to DMSO-treated rats (P < 0.001) and reduced the duration of convulsive seizures (P < 0.05). Seizure onset was increased significantly by SB-334867, 50 nmol, compared to DMSO (P < 0.05) and diazepam (P < 0.01) treated rats. CONCLUSION: Antagonism of orexin-A receptor by a low-dose SB-334867 showed protective effects in 4-AP-induced seizure-like activities in anesthetized rats.

Boswellia serrata Protects Against Glutamate-Induced Oxidative Stress and Apoptosis in PC12 and N2a Cells.

This study was designed to investigate whether the extract from Boswellia serrata oleo-gum resin (BSE) can protect against glutamate-induced oxidative damage and cytotoxicity in PC12 and N2a cell lines. Using a simple and reliable reverse-phase high-performance liquid chromatography (HPLC), the amount of 3-acetyl-11-keto-ß-boswellic acid (AKBA) in the BSE was found to be 18.5% w/w. The results confirmed that BSE and AKBA, at concentrations as high as 100 µg/mL or 10 µM, respectively, caused no significant cytotoxicity or apoptotic cell death. Co- and pretreatment with BSE (25-100 µg/mL) or AKBA (5 µM) restored the viability of PC12 and N2a cells under glutamate toxicity (8 mM). Treatment with BSE and AKBA also attenuated the toxic effects of glutamate on intracellular reactive oxygen species, lipid peroxidation, superoxide dismutase activity, and oxidative DNA damage compared with the untreated glutamate-injured cells. Furthermore, BSE and AKBA decreased the apoptotic cell population in the sub-G1 region and the rate of both early and late-stage apoptosis induced by glutamate in the cells. Our data suggest that the protective effects of Boswellia extract and AKBA against glutamate toxicity in PC12 and N2a cells may be mediated through the amelioration of the oxidative stress and the resultant apoptosis.

Renal injury, nephrolithiasis and Nigella sativa: A mini review.

OBJECTIVE: The incidence and prevalence of kidney stone is increasing worldwide. After the first recurrence the risk of subsequent relapses is higher and the time period between relapses is shortened. Urinary stones can be severely painful and make a huge economic burden. The stone disease may increase the vulnerability of patients to other diseases such as renal failure. Medicinal herbs are rich sources of antioxidants which are increasingly consumed globally for their safety, efficacy and low price. Nigella sativa is a spice plant that is widely used for prevention and treatment of many ailments in Muslim countries and worldwide. This review aims at investigation of the effects of Nigella sativa on renal injury and stone formation. MATERIALS AND METHODS: The scientific resources including PubMed, Scopus, and Google scholar were searched using key words such as: nephrolithiasis, urolithiasis, kidney/renal stone, renal injury, renal failure, urinary retention and black seed, black cumin, Nigella sativa and thymoquinone. RESULTS: N. sativa and its main component, thymoquinone showed positive effects in prevention or curing kidney stones and renal failure through various mechanism such as antioxidative, anti-inflammatory, anti-eicosanoid and immunomodulatory effects. The putative candidate in many cases has been claimed to be thymoquinone but it seems that at least in part, particularly in kidney stones, the herbal melanin plays a role which requires further investigation to prove. CONCLUSION: N. sativa and its components are beneficial in prevention and curing of renal diseases including nephrolithiasis and renal damages.

Beneficial Effect of Leptin on Spatial Learning and Memory in Streptozotocin-Induced Diabetic Rats.

BACKGROUND: Diabetes mellitus is a chronic disease which may be accompanied by cognitive impairments. The expression of the obesity gene (ob) is decreased in insulin-deficient diabetic animals and increased after the administration of insulin or leptin. Plasma leptin levels are reduced in the streptozotocin (STZ)-induced diabetic rats. Therefore, the deleterious effects of diabetes on memory may be due to the reduction of leptin. AIMS: Investigate the effect of subcutaneous injection of leptin on spatial learning and memory in STZ-induced diabetic rats. STUDY DESIGN: Animal experimentation. METHODS: The rats were divided into three groups: 1-control, 2- diabetic, and 3- diabetic-leptin. Diabetes was induced in groups 2 and 3 by STZ injection (55 mg/kg) intraperitoneally (i.p). The animals received leptin (0.1 mg/kg) or saline subcutaneously (s.c) for 10 days before behavioral studies. Then, they were examined in the Morris water maze over 3 blocks after 3 days of the last injection of leptin. RESULTS: The travelled path length and time spent to reach the platform significantly increased in the diabetic group (p<0.001) and decreased with leptin treatment (p<0.01 & p<0.001 respectively); also, a significant increase in path length and time was observed between the diabetic-leptin group and the diabetic group (p<0.01, p<0.001, respectively) in the probe test. CONCLUSION: Leptin can exert positive effects on memory impairments in diabetic rats.

The effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in hippocampus of STZ-induced diabetic rats.

OBJECTIVE: Oxidative stress plays an important role in the etiology of diabetic complications. Diabetes impairs hippocampus neurogenesis, synaptic plasticity, and learning. The aim of this study was to investigate the effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in STZ-induced diabetic rats' hippocampus. MATERIALS AND METHODS: Diabetes induced by 60 mg/kg STZ, i.p, and the rats were divided into five experimental groups (n=8-10 in each group) including control (received 0.5 ml normal saline), untreated STZ-diabetic (received 0.5 ml normal saline), and treated rats received Nigella sativa extract (200 and 400 mg/kg) or metformin (300 mg/kg) by gavage for 42 days. Serum glucose concentration and body weight as well as hippocampus tissue malondialdehyde and thiol levels were determined by calorimetric assay. RESULTS: Serum glucose level in the diabetic rats treated with 200 mg/kg Nigella sativa extract at the days 24 and 45 decreased in comparison to untreated diabetic group (p<0.05, p<0.01, respectively). Weight loss was significantly different between metformin and Nigella sativa extract at the dose of 200 and 400 mg/kg (p<0.05). Thiol content of hippocampus increased by 200 mg/kg Nigella sativa extract in comparison to untreated diabetic group (p<0.05). Malondialdehyde content of hippocampus reduced by Nigella sativa extract, 200 mg/kg (p<0.001), 400 mg/kg (p<0.05), and metformin (p<0.05) in comparison to the untreated diabetic group. CONCLUSION: The results of the present study showed that hydroalcoholic extract of the Nigella sativa decreased oxidative stress in hippocampus of the STZ-induced diabetic rats. Nigella sativa at the dose of 200 mg/kg was more effective to reduce oxidative stress in hippocampus of rats.

Effect of exogenous leptin on serum levels of lipids, glucose, renal and hepatic variables in both genders of obese and streptozotocin-induced diabetic rats.

OBJECTIVES: Leptin exerts various effects on appetite and body weight. Disruption of the obesity gene is precedent to fatness. Insulin or glucose elevates leptin, but streptozotocin reduces it. However, controversial data exist for the effects of leptin on diabetes and leptin level in each gender. Leptin can damage the kidney function but little evidence exists for its hepatic effects. The aim of this study was to investigate the probable sex-dependent differences in blood sugar levels, lipid profile, and renal and hepatic biochemical factors in the obesity and streptozotocin-induced diabetic rats after leptin administration. MATERIALS AND METHODS: Wistar rats of both sexes were randomly divided into two groups, namely obese and diabetic rats. Each group was further divided into male and female subgroups. Extra fat and carbohydrate was added to the diet to induce obesity. Furthermore, streptozotocin (55 mg/kg, IP) was injected to induce diabetes. The treatment groups received leptin (0.1 mg/kg SC) for 10 days, and then, blood samples were taken from the orbital sinus for laboratory evaluations. RESULTS: Leptin resulted in a significant weight loss in both sexes (P<0.001), food intake reduction in male rats (P<0.05), LDL reduction in female rats (obese (P<0.05) and diabetic (P<0.001)), and glucose level decline in the female diabetic rats (P<0.001). However, total protein concentration, LFT (liver function tests), urea and creatinin concentrations among different groups did not show any significant changes. CONCLUSION: Leptin caused some discrepant results, especially regarding the LDL and glucose levels in diabetic female rats.

Effects of melatonin on biochemical factors and food and water consumption in diabetic rats.

BACKGROUND: Diabetic neuropathy is one of the serious problems due to microvessel vasculopathy in diabetes. It has been reported that hyperglycemia and hypertriglyceridemia are the underlying mechanisms in inducing and progression of diabetic neuropathy. The aim of the present study was to investigate the effects of melatonin on serum glucose and lipid levels, as well as food consumption and water intake in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Eighty male Wistar rats were randomly assigned to six groups including; normal control group, diabetic control group and 4 diabetic experimental groups that received melatonin intraperitoneally at doses of 2.5, 5, 10, and 20 mg/kg at the end of sixth week after verification of neuropathy by means of evaluation of sciatic nerve conduction velocity (MNCV), for two weeks. Blood glucose and lipid levels, body weight, the amounts of food consumption, and water intake were determined in all groups at weeks 0 (before diabetes induction), 3, 6, and at the end of eighth week. RESULTS: Treatment with melatonin reduced significantly the serum glucose (P < 0.001) and triglyceride (P < 0.05) levels, food consumption (P < 0.001), and water intake (P < 0.001) in diabetic rats at the end of eighth week. However, melatonin had no significant effect on body weight of diabetic animals. CONCLUSIONS: Treatment with melatonin could improve several signs of diabetes, including hyperglycemia, hypertriglyceridemia, polyphagia, and polydipsia. Therefore, melatonin may be used as an adjunct therapy in the treatment of diabetes.