Antiapoptotic and neuroprotective role of Curcumin in Pentylenetetrazole (PTZ) induced kindling model in rat.

Kindling, a sub threshold chemical or electrical stimulation, increases seizure duration and enhances accompanied behavior until it reaches a sort of equilibrium state. The present study aimed to explore the effect of curcumin on the development of kindling in PTZ kindled rats and its role in apoptosis and neuronal damage. In a PTZ kindled Wistar rat model, different doses of curcumin (100, 200 and 300 mg/kg) were administrated orally one hour before the PTZ injections on alternate day during the whole kindling days. The following parameters were compared between control and experimental groups: the course of kindling, stages of seizures, Histopathological scoring of hippocampus, antioxidant parameters in the hippocampus, DNA fragmentation and caspase-3 expression in hippocampus, and neuron-specific enolase in the blood. One way ANOVA followed by Bonferroni post hoc analysis and Fischer’s Exact test were used for statistical analyses. PTZ, 30 mg/kg, induced kindling in rats after 32.0±1.4 days. Curcumin showed dose-dependent anti-seizure effect. Curcumin (300 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure score and decreased the number of myoclonic jerks. PTZ kindling induced a significant neuronal injury, oxidative stress and apoptosis which were reversed by pretreatment with curcumin in a dose-dependent manner. Our study suggests that curcumin has a potential antiepileptogenic effect on kindling-induced epileptogenesis.

Evaluation of effect of isoflavone on thyroid economy & autoimmunity in oophorectomised women: A randomised, double-blind, placebo-controlled trial.

Background and objectives: The potential of soy isoflavones to interfere with thyroid function has been reported. However, there are limited data regarding their effect on thyroid function and autoimmunity in surgical menopausal women. The present study aimed to evaluate the effect of isoflavones on thyroid function and autoimmunity, menopausal symptoms, serum follicle stimulating hormone (FSH) and estradiol levels in oophorectomised women. Methods: A randomized, double blind, placebo-controlled trial was conducted in 43 oophorectomised women to evaluate the effect of soy isoflavones (75 mg/day for 12 wk) on serum thyroid profile (free T3 , free T4 , TSH, TBG and anti-TPO antibody titres) assessed at baseline, 6 and 12 wk after randomization. Assessment was also done for menopause symptom score (MSS) three weekly, and FSH and estradiol levels at baseline and at study completion. Results: There was a significant alteration in free T 3 levels in the group receiving isoflavones (4.05 ± 0.36, 4.12 ± 0.69 and 3.76 ± 0.55 pmol/l at baseline, 6 and 12 wk, respectively; P=0.02). However, the mean change in various thyroid parameters at 12 wk from baseline was not significantly different between the two groups. MSS was also significantly decreased at 9 and 12 wk from baseline with isoflavones (12.47 ± 8.15, 9.35 ± 5.23 and 9 ± 5.14 at baseline, 9 and 12 wk respectively; P=0.004) with significant improvement in urogenital symptoms compared to placebo. Isoflavones did not significantly affect other parameters during study period. There were no serious adverse events reported and the proportion of patients experiencing adverse events was similar between the two groups. Interpretation and conclusions: Modest reduction in serum free T3 levels in the isoflavone group in the absence of any effect on other thyroid parameters might be considered clinically unimportant.

Neuroprotective effect of pioglitazone on acute phase changes induced by partial global cerebral ischemia in mice.

Present study was carried out to investigate the possible neuroprotective effect of pioglitazone, an antidiabetic agent, peroxisome proliferator-activated receptor (PPAR) agonist on acute phase changes in mice model of cerebral ischemia induced by Bilateral Common Carotid artery Occlusion (BCCAO). BCCAO model was used to induce partial global cerebral ischemia. BCCAO induced significant brain infarct size and edema in saline treated control group along with high increase in oxidative stress showed by increase lipid peroxidation and decreased levels of antioxidants like superoxide superoxide dismutage, catalase, glutathione peroxidase. Pioglitazone (20 mg/kg, orally) administration showed neuroprotective effects by reducing cerebral infarct size significantly as compared to control group. Postischemic seizure susceptibility was also reduced as number of positive responders decreased to a significant number. Brain edema was subsided to a significant level. Pioglitazone reduced the plasma TNF- α levels as compared to ischemia group significantly. Pioglitazone treatment also improved all the antioxidants levels showing activity against oxidative stress induced by BCCAO. Pioglitazone showed neuroprotection against ischemic insult suggesting the role of PPAR agonist in neuroprotective agents.