effect of green tea extract on oxidative stress and spatial learning in streptozotocin-diabetic rats

Diabetes mellitus is associated with distribution of cognitive functioning. Hyperglycemia induced oxidative stress has been proposed as a cause of memory complications of diabetes including cognitive impairment. The aim of this study was to examine total green tea extract [TGTE], a potent free radical scavenger against spatial impairment in Streptozotocin-diabetic rats. Eight weeks after diabetes induction, TGTE was administrated throught drinking water 3 mg/L. The learning and memory behavior was evaluated with Morris water maze task in male rats. Then, for estimation of oxidative stress parameters such as lipid peroxidation [LPO], total antioxidant capacity [FRAP] and total thiol groups in blood were measured. The total green tea extract showed improved cognitive impairment in diabetic groups but these changes weren't significant. There was also significant increase FRAP level and total thiol groups in treated green tea groups vs. control. group. This study demonstrated the effectiveness of TGTE on spatial impairment and oxidative stress induced in diabetes mellitus

Propofol attenuates toxic oxidative stress by CCl4 in liver mitochondria and blood in rat

Anti-oxidant effects of propofol [2, 6-diisopropylphenol] were evaluated agains carbon tetrachloridet CCl[4] -induced oxidative stress in rat liver. 30 male rats were equally divided in to 6 groups [5 rats each]. Group I [control], while Group II was given CCl[4] [3 mL /Kg/day, IP]. Animals of Groups III received only propofol [10 mg/Kg/day, IP]. Group IV was given propofol+ CCl[4]. Group V was administered vitamin E [alpha-tocopherol acetate 15 mg/Kg/day, SC] .Animals of Group VII received alpha-tocopherol acetate + CCl[4] once daily for two weeks. After treatment, blood and liver mitochondria were isolated. Anti-oxidant enzymes activity such as glutathione peroxidase [GPx], superoxide dismutase [SOD] and oxidative stress marker such as reduced glutathione [GSH] and lipid peroxidation [LPO] concentration were measured. Oxidative stress induced with CCl[4] in liver mitochondria was evident by a significant increase in enzymatic activities of GPx, SOD, and LPO and decreased of GSH and vailability of mitochondria. Propofol and vitamin E restored CCl[4]-induced changes in GSH, GPx, SOD and LPO in blood and liver mitochondria. CCl[4] decreased viability of mitochondria that was recovered by propofol and vitamin E. It is concluded that oxidative damage is the mechanism of toxicity of CCl[4] in the mitochondria that can be recovered by propofol comparable to vitamin E

Effects of lithium on peripheral neuropathy induced by vincristine in rats

Vincristine [VCR] as a frequently used antimitotic agent which is commonly prescribed for wide spectrum of neoplasm, causes mixed sensorimotor neuropathy. Several evidences show lithium could be a neuroprotective agent, therefore to assess whether a pretreatment and at subtherapeutic dose it could prevent the peripheral neuropathy produced by VCR, rats were treated with VCR 0.1mg/kg i.p. for 3 alternative doses and / or lithium chloride [20mg/kg or 40 mg/kg i.p. daily from the first day to the day of sacrifice]. Erythrocyte lithium concentration [ELC] and plasma lithium concentration [PLC] were measured at the seventh day of study and the day of scarification. After seventh day of lithium administration, PLC and ELC reached to a steady state at subtherapeutic dose and they did not significantly change at normal housing situation. Hot plate, open field test and nerve conduction velocity were used to evaluate the sensory and motor neuropathy. Only VCR treated rats showed behavioral, electrophysiological and histological evidences of a mixed sensorimotor neuropathy by significant increase in hot plate latencies and a marked decrease in total distance moved and conduction velocities in both sensory and motor nerves. Lithium at the dose of 20mg/kg and specially 40mg/kg robustly reduced the rate of mortality, general toxicity and was able to ameliorate mixed sensorimotor neuropathy induced by VCR. These results suggest that lithium at dose of 20mg/kg and 40 mg/kg, potentially by its effects on cell survival pathways such as inhibition of glycogen synthase kinase-3 [GSK3beta], can prevent both motor and sensory components of VCR neuropathy

Lead exposure impairs NMDA agonist-induced no production in pyramidal hippocampal cells

Chronic exposure to Lead [Pb] affects neural functions in central nervous system [CNS] particularly the learning and memory. On the other hand, alteration of calcium level in the CNS results in activation of NOS where it is expected to increase nitric oxide level in hippocampus. In this study the role of Lead exposure in NMDA induced NO production in pyramidal hippocampal cells [CA1HP] was investigated. The NO level was determined by measurement of concentration of nitrite and nitrate as NO products using the metHb production at 401 nm. The ACBD [NMDA agonist]-induced NO level was almost reduced to the control level [2.5 nM] in the presence of 10 and 100 nM of Lead acetate. Lead acetate at concentrations which normally results in chronic toxicity did not increase the nitric oxide [NO] production by CA1HP. One reason for this finding could be the interaction of Lead with NMDA receptors due to similarity of Pb[2+] to Zn[2+] ion. Another reason may be related to direct interaction of Lead with NMDA receptors that inhibit the stimulated NO production

Anticonvulsant activities of 7-phenyl-5H-thiazolo[5, 4-e][1, 2, 3, 4] tetrazolo[5, 1-c] pyrrolo[1, 2-alpha][1, 4] diazepine and 7-phenyl-5H-thiazolo[5, 4-e][1, 3, 4] triazolo[5, 1-c] pyrrolo[1, 2-alpha][1, 4] diazepines

Anticonvulsant activity of 7-phenyl-5H-thiazolo[5, 4-e][1, 2, 3, 4]tetrazolo[5, 1-c]pyrrolo[1, 2-a][1, 4]diazepine [5] and 7-phenyl-5H-thiazolo[5, 4-e][1, 3, 4]triazolo[5, 1-c]pyrrolo[1, 2-a][1, 4]diazepines [6a-d] was measured against pentylenetetrazole [PTZ]-induced seizures in mice. Intraperitoneal injections of different doses [12.5, 25 and 50 mg/kg, i.p.] of test compounds decreased PTZ-induced seizure significantly in a dose-dependent manner.The test compounds were administered 30 min befor PTZ [80 mg/kg, i.p.] injection. The maximum response was obtained with 50 mg/kg of compound 6d that showed more anticonvulsant activity compared to diazepam [0.5 mg/kg]. The frequency of mortality was also decreased by all listed compounds. Pretreatment of animals with flumazenile [as a benzodiazepine, BDZ receptor antagonist] decreased, but not completely inhibited the anticonvulsant activity of compound 6d [50 mg/kg]. These results indicate that besides BZD receptors, other neurotransmitter systems may be involved in anticonvulsant activity of the tested compounds

Anticonvulsant activities of new 1,4-dihydropyridine derivatives containing 4-nitroimidazolyl substituents

Anticonvulsant activity of Alkyl, cycloalkyl and arylalkyl ester analogues of nifedipine in which the ortho-nitro phenyl group at position 4 is replaced by 1-methyl-4-nitro-5-imidazolyl substituent, were determined against pentylenetetrazole-induced seizures in mice. The anticonvulsant effects of the compounds were evaluated by the measurement of seizure latency and duration. Significant differences were observed between treated animals with control group and nifedipine in seizure duration. Our results show that most of the compounds had similar activity to the reference drug nifedipine. In addition, compounds 6a, 6b, 6f, 6g, 6h, 8e, 8f, 8g, 8h and 8i were more active than the reference drug nifedipine

Syntheses and anticonvulsant activity of N4-substituted triazolylthiazoles

Due to the good anticonvulsant activity of various 1,2,4-triazoles, several new N4-substituted triazolylthiazoles were prepared by the general method for 1,2,4-triazole ring closure. Anticonvulsant activity of compounds was measured against pentylenetetrazole-induced seizures in mice by intraperitoneal injections of different doses of the test compounds. Pretreatment of animals with flumazenil [10 mg/kg, i.p.] as a benzodiazepine receptors antagonist did not have any significant effect on anticonvulsant activity of the test compounds. These results demonstrate that the anticonvulsant activity of N4-substituted triazolylthiazole agents is not probably mediated by direct interaction with benzodiazepine receptor complex