digitoxigenin and Seizures

Epilepsy is a common chronic disease of the central nervous system that can last for years or even decades, causing serious adverse effects on the body, mind, and psychology of patients. Traditional antiepileptic drugs can effectively control seizures, but because of large individual differences, serious adverse reactions, narrow therapeutic window and other shortcomings, more effective, new treatment drugs are looked for. Streptocaulon griffithii is a plant of Asclepiadaceae. 16-O-acetyldigitoxigenin (ACE) is a strong cardiac glycoside isolated from methanol extract of Streptocaulon griffithii. The aim of this study was to investigate the antiepileptic effect of ACE on Pilocarpine (Pilo) induced epilepsy in mice, and to explore the effect of mTOR signaling pathway on its antiepileptic effect. The results showed that ACE had antiepileptic and neuroprotective effects on Pilo induced epilepsy mice. ACE attenuates Pilo induced seizures by inhibiting the activation of p-mTOR/p-70S6K pathway, and inhibits Pilocarpine induced brain damage by inhibiting mTOR signaling pathway. These results suggest that ACE has a promising future in the treatment of epilepsy and other nervous system diseases.

Topics: Animals; Anticonvulsants; Apocynaceae; Caspase 3; Digitoxigenin; Drugs, Chinese Herbal; Epilepsy; Hippocampus; Interleukin-1beta; Male; Mice; Mice, Inbred ICR; Neurons; Neuroprotective Agents; Pilocarpine; Ribosomal Protein S6 Kinases, 90-kDa; Seizures; Signal Transduction; TOR Serine-Threonine Kinases; Tumor Necrosis Factor-alpha

Intravenous administration of digitoxigenin (DTXGN) evokes seizure episodes in mice which may be dependent on brain biogenic amines such as serotonin (5-HT). Fasting is known to have effects on both drug toxicity and brain 5-HT synthesis. The purpose of this study was to assess the effects of overnight fasting on DTXGN toxicity. The i.v. LD-50 of DTXGN was increased by 61% in fasted mice. Adjustment of DTXGN dose for the decrease in body weight of fasted mice did not alter the fasting induced protection. A loading dose of 1-tryptophan (25 mg/kg, i.p.) did not alter mortality rates in either fed or fasted mice. Cortical levels of 3H-DTXGN were decreased significantly by 25% in fasted mice. Liver and blood levels were elevated significantly. These data suggest that decreased DTXGN toxicity is associated with a decrease in its distribution to the cerebral cortex and emphasize the importance of acute dietary status in the expression of drug toxicity.

Topics: Animals; Body Weight; Digitoxigenin; Fasting; Lethal Dose 50; Liver; Male; Mice; Organ Size; Seizures; Serotonin; Tissue Distribution; Tryptophan

EEG was recorded from several brain regions during the i.v. infusion of digitoxigenin to conscious, freely-moving rats. Two seizure episodes were recorded from the ventral hippocampus with the second, more severe seizure characterized by low-frequency (3-6/sec), high-amplitude (0.9-1.5 mV) discharges. Secondary activity was recorded from the mesencephalic and reticular formations. Pretreatment of rats with p-chlorophenylalanine or reserpine prevented the first seizure and markedly delayed the second seizure to appear after 1.85 mg or 4.66 mg digitoxigenin/kg, respectively, compared to 0.79 mg/kg in untreated rats. The pretreatments did not alter the frequency of the discharges but reduced their amplitude to 0.4 -0.75 mV. The results suggest a role for monoamines, and in particular serotonin, in the effect of digitoxigenin to cause hippocampal seizure discharge.

Topics: Animals; Digitoxigenin; Fenclonine; Hippocampus; Male; Rats; Rats, Inbred Strains; Reserpine; Seizures

The uptake of 3H-digitoxigenin (3H-DIGT), administered by intravenous infusion to conscious, unrestrained rats, increased with time in the medulla-pons, cerebellum, cerebral cortex, corpus striatum, hippocampus, hypothalamus, and midbrain coincident with the development of behavioral and motor disruption. At four minutes of infusion, during clonic convulsions, uptake appeared to follow reported differences in regional blood flow, ranging from 0.48 microgram/gm (hypothalamus) to 0.67 microgram/gm (cerebellum). After 5 1/2 minutes of infusion, rats still in clonic convulsions had no further increase in uptake; rats entering tonic convulsions had two- to three-fold increases in 3H-DIGT uptake, ranging from 1.00 microgram/gm (hypothalamus) to 1.65 microgram/gm (cerebellum). Electroshock-induced tonic convusions at 2 minutes of infusion increased 3H-DIGT uptake two- to three-fold in all regions, suggesting that the increased neuronal activity associated with the tonic convulsion enhanced the uptake of 3H-DIGT into all regions. The only significant monamine alteration was a slightly decreased medulla-pons serotonin level after 5 1/2 minutes of infusion.

Topics: Animals; Behavior, Animal; Biogenic Amines; Brain; Digitoxigenin; Electroshock; Male; Rats; Seizures

Topics: Animals; Biogenic Amines; Brain; Brain Chemistry; Depression, Chemical; Digitoxigenin; Electroshock; Fenclonine; Male; Methyltyrosines; Mice; Mice, Inbred ICR; Pentylenetetrazole; Reserpine; Seizures

Topics: Animals; Brain Chemistry; Digitoxigenin; Electroshock; Fenclonine; Male; Methyltyrosines; Pentylenetetrazole; Rats; Reserpine; Seizures; Serotonin

Topics: Animals; Biogenic Amines; Digitalis Glycosides; Digitoxigenin; Mice; Norepinephrine; Seizures; Serotonin