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.

Protective effects of ascorbic acid and garlic extract against lead-induced apoptosis in developing rat hippocampus.

Lead exposure has negative effects on developing nervous system and induces apoptosis in newly generated neurons. Natural antioxidants (i.e. Ascorbic acid and Garlic) might protect against lead-induced neuronal cell damage. The aim of the present study was to investigate the protective effects of Ascorbic acid and Garlic administration during pregnancy and lactation on lead-induced apoptosis in rat developing hippocampus. Timed pregnant Wistar rats were administrated with Lead (1500 ppm) via drinking water (Pb group) or lead plus Ascorbic acid (Pb + AA Group, 500 mg/kg, IP), or lead plus Garlic Extract (Pb + G Group, 1 ml garlic juice/100 g BW, via Gavage) from early gestation (GD 0) until postnatal day 50 (PN 50). At the end of experiments, the pups' brains were carefully dissected. To identify neuronal death, the brain sections were stained with TUNEL assay. Mean of blood and brain lead levels increased significantly in Pb group comparing to other studied groups (P < 0.01). There was significant reduction in blood and brain lead level in Pb + AA and Pb + G groups when compared to those of Pb group (P < 0.01). The mean number of TUNEL positive cells in the CA1, CA3, and DG was significantly lower in the groups treated by either Ascorbic acid or Garlic (P < 0.05). Administration of Ascorbic acid and Garlic during pregnancy and lactation protect against lead-induced neuronal cell apoptosis in the hippocampus of rat pups partially via the reduction of Pb concentration in the blood and in the brain.

Estrogen-dependent effect of soy extract on pentylenetetrazole-induced seizures in rats.

OBJECTIVE: To study the different effects of soy extract on pentylenetetrazole (PTZ)-induced seizures in the presence and absence of ovarian hormones in rats, and the gender-dependent differences in the effects of phytoestrogens on behavior. METHODS: Male and female Wistar rats were randomly divided into nine groups with eight in each, namely, male-saline (M-saline), male-low-dose soy (M-LDS), male-high-dose soy (M-HDS), sham-saline (Sh-saline), sham-low-dose soy (Sh-LDS), sham-high-dose soy (Sh-HDS), ovariectomized-saline (OVX-saline), ovariectomized-low-dose soy (OVX-LDS) and ovariectomized-high-dose soy (OVX-HDS). The rats of groups 7 to 9 were ovariectomized under ketamine anesthesia. The rats of groups 2, 5 and 8 were treated by 20 mg/kg of soy extract while the animals of groups 3, 6 and 9 received 60 mg/kg of soy extract for two weeks. In groups 1, 4 and 7, saline was injected instead of soy extract. The animals were then injected by a single dose of PTZ (90 mg/kg body weight, intraperitoneally) and placed in a plexiglas cage and the latency to minimal clonic seizure (MCS) and generalized tonic-clonic seizure (GTCS) was recorded. RESULTS: Both MCS and GTCS latency in M-LDS and M-HDS groups was significantly lower than that in M-saline group (P<0.05 or P<0.01). Treatment for female sham rats by soy extract did not affect MCS and GTCS latency. The animals of OVX-LDS and OVX-HDS groups had lower MCS and GTCS latency in comparison with OVX-saline group (P<0.05 or P<0.01). CONCLUSION: It is concluded that the phytoestrogens of soy affect seizure severity induced by PTZ, but their effects are different in the presence or absence of ovarian hormones. However, further studies are necessary to be done.

Effects of soy extract on pentylenetetrazol-induced seizures in ovariectomized rats.

OBJECTIVE: To investigate the effects of soy extract on pentylenetetrazol (PTZ)-induced seizures in ovariectomized (OVX) rats. METHODS: Female Wistar rats were randomly divided into 4 groups (n=15 in each group) as follows: sham-operated, OVX, low-dose soy (LDS) and high-dose soy (HDS). The rats in each group were divided into two subgroups and received daily injection of a low dose of PTZ (40 mg/kg body weight, intraperitoneally, n=7 in each subgroup) for 14 d or a single injection of a high dose of PTZ (90 mg/kg body weight, intraperitoneally, n=8 in each subgroup). The rats of LDS and HDS groups were injected with 20 and 60 mg/kg body weight of soy extract intraperitoneally, respectively, just 30 min before each PTZ injection. The rats of the sham-operated and the OVX groups received saline instead of soy extract. After treatment, the rats were placed in a plexiglas cage and their behaviors were observed for 60 min. RESULTS: The results of repeated injection of low dose of PTZ during 14 d showed that the seizure score of the rats of OVX group on days 3, 5, 8, 10, 11, 12, and 13 was lower than that of the sham-operated group (P<0.05 or P<0.01). However, the rats of both LDS and HDS groups had higher score compared with the OVX group on the mentioned days (P<0.05 or P<0.01). The results of a single injection of a high dose of PTZ showed a significant increase (P<0.01) in the generalized tonic-clonic seizure (GTCS), but not the minimal clonic seizure (MCS) in the OVX rats compared with the sham-operated rats. Treatment with both low and high doses of soy extract significantly decreased the GTCS and MCS latencies compared with the OVX group (P<0.01). CONCLUSION: Female hormones affect seizure severity induced by PTZ, and phytoestrogens of soy mimic this effects. However, more investigations need to be done in the future.