Protective effects of Smyrnium cordifolium boiss essential oil on pentylenetetrazol-induced seizures in mice: involvement of benzodiazepine and opioid antagonists.

Smyrnium cordifolium as a wild plant is used in traditional medicine in Iran for the treatment of anxiety and insomnia. The anticonvulsant effect of this plant has not been studied to date, therefore this study aimed to evaluate the anticonvulsant effects of its essential oil and curzerene on seizure. Essential oil of the Smyrnium cordifolium plant was prepared by the hydro-distillation method. Gas chromatography and gas chromatography-mass spectroscopy analysis of the essential oil revealed its main components. Anticonvulsant effects of Smyrnium cordifolium essential oil (SCEO) and curzerene were examined on mice using the pentylentetrazole model (PTZ). Flumazenil (2 mg/kg, i.p) and naloxone (5 mg/kg, i.p) were injected into the relevant groups of mice to realize the anticonvulsant mechanism of SCEO and curzerene, respectively. The main identified components of the plant were curzerene (65.26%), δ-Cadinene (14.39%) and γ-elemene (5.15%), which comprised approximately 85.28% of SCEO. The ED50 values of SCEO and curzerene in the PTZ model were 223±15 and 0.25±0.09 mg/kg, respectively. Curzerene at the dosage of 0.4 mg/kg prolonged the onset time of seizure and decreased the duration of seizure among treated group compared to the saline group. At the dosage of 0.4 mg/kg, seizure and mortality protection rates for the treated group were 100%. Flumazenil and naloxone could suppress the anticonvulsant effects of SCEO and curzerene. It seems that SCEO and curzerene are useful for the treatment of absence seizure and this effect may be related to their effects on GABAergic and opioid systems.

Protection of human and murine hepatocytes against Fas-induced death by transferrin and iron.

Recent studies in a murine model show that transferrin (Tf) interferes with Fas-mediated hepatocyte death and liver failure by decreasing pro-apoptotic and increasing anti-apoptotic signals. We show here in vitro in murine and human hepatocyte cell lines and in vivo in mice that Fas-induced apoptosis is modulated by exogenous Tf and iron. The results obtained with iron-free Tf (ApoTf), iron-saturated Tf (FeTf), and the iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH) in its iron-free and iron-saturated (FeSIH) forms indicate that apoptosis-modulating effects of Tf are not mediated by iron alone. Both the Tf molecule and iron affect multiple aspects of cell death, and the route of iron delivery to the cell may be critical for the final outcome of cellular Fas signaling. Survival of hepatocytes 'stressed' by Fas signals can be manipulated by Tf and iron and may be a target for prophylactic and therapeutic interventions.