Neuroprotective effects of the fractions of Ocimum basilicum in seizures induced by pentylenetetrazole in mice.

Objective: Neuroprotective and antioxidant effects of Ocimum basilicum (O. basilicum) against pentylenetetrazole (PTZ)-induced seizures were investigated. Materials and Methods: Mice were divided as follows: (Group 1) Control, (Group 2) PTZ, (Groups 3-5) 50,100 and 200 mg/kg hydro-ethanolic (HE) extract, and (Groups 6-8) 200 mg/kg ethyl-acetate (EAF), N-hexane (NHF) and water (WF) fractions. Minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) latencies were measured. Biochemical and histological studies were done. Results: MCS and GTCS latency in HE groups were longer than the PTZ group (p<0.05 to p<0.001). EAF and NHF prolonged the onset of MCS and GTCS (p<0.001). PTZ increased malondialdehyde (MDA) and dark neuron (DN) production while decreased thiol, catalase (CAT) and superoxide dismutase (SOD) (p<0.05 to p<0.001). Pre-treatment by HE and all fractions of the plant attenuated MDA and DN while increased thiol, CAT and SOD (p<0.01 to p<0.001). Conclusion: EAF and NHF had anticonvulsant properties. The extract and fractions protected the brain from PTZ-induced oxidative damages and showed neuroprotective effects.

Neuroprotective effects of Pinus eldarica in a mouse model of pentylenetetrazole-induced seizures.

OBJECTIVE: Oxidative stress has pernicious effects on the brain. Pinus eldarica has antioxidant properties. We explored neuroprotective effect of P. eldarica against pentylenetetrazole (PTZ)-induced seizures. MATERIALS AND METHODS: Male mice (BALB/c) were grouped as control, PTZ, Soxhlet (Sox) 100, Sox 200, Macerated (Mac) 100 and Mac 200 groups. Sox and Mac extracts (100 and 200 mg/kg) were injected during 7 days. Delay in onset of minimal clonic seizure (MCS) and generalized tonic- clonic seizure (GTCS) was measured. Number of dark neurons (DN) and levels of oxidative stress indicators in the hippocampus were evaluated. RESULTS: Onset of MCS and GTCS was later in groups treated with the extracts than the PTZ group (p<0.01 and p<0.001). Number of DN in the hippocampus in the PTZ group was higher than the control group (p<0.001) while in the extract groups, was lower than the PTZ group (p<0.05, p<0.01 and p<0.001). MDA level was higher whereas total thiol level and activity of SOD and CAT were lower (p<0.001) in the PTZ group than the control group. MDA level in the Sox 100 (p<0.01), Sox 200 (p<0.001) and Mac 200 (p<0.01) groups was less than the PTZ group. Total thiol level in the Sox 200 (p<0.001), SOD in the Sox 100 (p<0.05), Sox 200, and Mac 200 and CAT in the Sox 200 (p<0.001) groups were higher than the PTZ group. CONCLUSION: P. eldarica prevented neuronal death and reduced seizures caused by PTZ via improving brain oxidative stress.

Hepatoprotective Impact of Ghrelin against Cyclophosphamide-Induced Toxicity in the Male Mice.

BACKGROUND: Despite its vast spectrum of clinical usage, cyclophosphamide (CP) exerts many adverse impacts, including hepatotoxicity. Antioxidant properties of ghrelin might protect the liver from CP-induced toxicity. The current study aimed to assess the protective impacts of ghrelin on CP-induced liver toxicity. METHODS: Forty male mice were randomly divided into four groups (n=10) Group 1 as control received no intervention,group 2 received cyclophosphamide (CP) (100 mg/kg, i.p.) for five weeks and once a week. Group 3 received CP+ghrelin (CP+G), (80 µg/kg daily, i.p.) for five weeks. Group 4 received ghrelin with above-mentioned dose. At the end of the experiment, the mice were sacrificed to remove liver tissuesfor histological and biochemical examination. RESULTS: Malondialdehyde (MDA) level increased after CP treatment but ghrelin administration significantly decreased the level of MDA (P<0.05). Measurement of the total antioxidant capacity (TAC) noted a significant decrease in the CP group against the control group (P<0.05). Ghrelin treatment in the CP+G group considerably increased the TAC activity when compared to the CP group (P<0.05). Histological examinations also confirmed the hepatocyte necrosis, local bleeding and inflammation, vacuolation, and sinusoidal dilation in the CP group, ghrelin administration reduced the destructive effects of CP on the liver significantly (P<0.05). CONCLUSION: Our results reveal the hepatoprotective effect of ghrelin against CP. Therefore, ghrelin might be useful in protecting the body against the adverse impacts of injuries induced by chemotherapeutic drugs.

Neuroprotective and long term potentiation improving effects of vitamin E in juvenile hypothyroid rats.

Protective effects of vitamin E (Vit E) on long term potentiation (LTP) impairment, neuronal apoptosis and increase of nitric oxide (NO) metabolites in the hippocampus of juvenile rats were examined. The rats were grouped (n=13) as: (1) control; (2) hypothyroid (Hypo) and (3) Hypo-Vit E. Propylthiouracil (PTU) was given in drinking water (0.05%) during 6 weeks. Vit E (20 mg/ kg) was daily injected (IP). To evaluate synaptic plasticity, LTP from the CA1 area of the hippocampus followed by high frequency stimulation to the ipsilateral Schafer collateral pathway was carried out. The cortical and hippocampal tissues were then removed to measure NO metabolites. The brains of 5 animals in each group were removed for apoptosis study. The hypothyroidism status decreased the slope, 10-90% slope and amplitude of field excitatory post synaptic potential (fEPSP) compared to the control group (P<0.01-P<0.001). Injection of Vit E increased the slope, 10-90% slope and amplitude of the fEPSP in the Hypo-Vit E group in comparison to the Hypo group (P<0.05-P<0.01). TUNEL positive neurons and NO metabolites were higher in the hippocampus of the Hypo rats, as compared to those in the hippocampus of the control ones (P<0.001). Treatment of the Hypo rats by Vit E decreased apoptotic neurons (P<0.01-P<0.001) and NO metabolites (P<0.001) in the hippocampus compared to the Hypo rats. The results of the present study showed that Vit E prevented the LTP impairment and neuronal apoptosis in the hippocampus of juvenile hypothyroid rats.

The effects of soy and tamoxifen on apoptosis in the hippocampus and dentate gyrus in a pentylenetetrazole-induced seizure model of ovariectomized rats.

The effects of tamoxifen and soy on apoptosis of the hippocampus and dentate gyrus of ovariectomized rats after repeated seizures were investigated. Female rats were divided into: (1) Control, (2) Sham, (3) Sham-Tamoxifen (Sham-T), (4) Ovariectomized (OVX), (5) OVX-Tamoxifen (OVX-T), (6)OVX-Soy(OVX-S) and (7) OVX-S-T. The animals in the OVX-S, OVX-T and OVX-S-T groups received soy extract (60 mg/kg; i.p.), tamoxifen (10 mg/kg) or both for 2 weeks before induction of seizures. The animals in these groups additionally received the mentioned treatments before each injection of pentylenetetrazole (PTZ; 40 mg/kg) for 6 days. The animals in the Sham and OVX groups received a vehicle of tamoxifen and soy. A significant decrease in the seizure score and TUNEL-positive neurons was seen in the OVX group compared to the Sham (P < 0.001). The animals in both the OVX-T and OVX-S groups had a significantly higher seizure score as well as number of TUNEL-positive neurons compared to the OVX group (P < 0.01-P < 0.001). Co-treatment of the OVX rats by the extract and tamoxifen decreased the seizure score and number of TUNEL-positive neurons compared to OVX-S (P < 0.001). Treatment of the OVX rats by either soy or tamoxifen increased the seizure score as well as the number of TUNEL-positive neurons in the hippocampal formation. Co-administration of tamoxifen and soy extract inhibited the effects of the soy extract and tamoxifen when they were administered alone. It might be suggested that both soy and tamoxifen have agonistic effects on estrogen receptors by changing the seizure severity.

The effects of tamoxifen and soy on dark neuron production in hippocampal formation after pentylenetetrazole-induced repeated seizures in rats.

BACKGROUND: Regarding the similar modulatory effects of both soy and tamoxifen on the actions of estrogen which have previously reported, the aim of the present study was to investigate the effects of these two estrogen like compounds alone and in combination on dark neuron production in hippocampal formation of ovariectomized rats after pentylenetetrazole-induced repeated seizure. METHODS: The rats were randomly divided into six groups: control, sham, OVX, OVX-soy (OVX-S), OVX-tamoxifen (OVX-T) and OVX-soy-tamoxifen (OVX-S-T). The animals of OVX-S, OVX-T and OVX-S-T groups received the soy extract (60mg/kg; i.p.), tamoxifen (10mg/kg) or both for 2 weeks before induction of seizures. The animals of these groups were also treated by soy extract, tamoxifen or both before each injection of PTZ (40mg/kg) for 6 days. The animals of sham and OVX groups received saline plus tween instead of tamoxifen and soy extract. The animals of control group did not treat by PTZ, tamoxifen and soy. The rats were placed in Plexiglas cages separately and observed for 60min. The brain tissues were then removed and subjected for histological studies. RESULTS: A significant decrease in the seizure score was seen in OVX group comparing to sham. The animals of both OVX-T and OVX-S groups had a significant higher seizure score compared to OVX group. Co-treatment of the ovariectomized rats by both soy extract and tamoxifen decreased the seizure score compared to OVX-S and OVX-T groups. The results of histological study showed that the dark neuron number in CA1, CA2, CA3 and dentate gyrus (DG) of hippocampus area in OVX-T and OVX-S groups was higher than that of OVX group (P<0.05-P<0.01). In CA3, the produced dark neurons of OVX-S-T group were lower than that OVX-S group (P<0.01). CONCLUSION: The results of present study showed that treatment of the ovariectomized rats by either soy extract or tamoxifen increased the seizure score as well as dark neurons. Co-treatment with soy extract and tamoxifen did not potentiate the effects of each of them alone. Co-administration of the tamoxifen and soy extract inhibited the effects of the soy extract and tamoxifen when they administered alone.