Banca de QUALIFICAÇÃO: IGOR RAFAEL PRAXEDES DE SALES

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : IGOR RAFAEL PRAXEDES DE SALES
DATE: 07/10/2021
TIME: 14:00
LOCAL: meet.google.com/vjp-rcxs-xtn
TITLE:

PHYTOCHEMICAL CHARACTERIZATION AND ANTICONVULSANT ACTIVITY OF PHYTOCANABINOIDS IN A STATUS EPILEPTICUS ANIMAL MODEL

KEY WORDS:

status epilepticus, natural products, hippocampus, pilocarpine, cannabinoids and entourage effect.

PAGES: 80
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUMMARY:

Placebo-controlled clinical trials show that cannabidiol (CBD) is a drug with anti-seizure properties that reduces frequency of seizures, convulsive or not, in difficult-to-control epilepsies. It was found that CBD effect involves interaction with other drugs such as clobazam and mechanism of action does not directly involve endocannabinoid system activation. Some phytocannabinoids modulate neuronal excitability, therefore the purpose of this work is to evaluate the effect of two extracts with a full spectrum phytocannabinoid profile on status epilepticus (SE). We hypothesized that extracts derived from Cannabis, as they contain a variety of secondary metabolites, are more effective than a pure phytocannabinoid (CBD salt) in controlling neuronal hyperexcitability. In pharmacological tests, we compared the anticonvulsant activity of extracts in intrahippocampal pilocarpine-induced SE model in mice (CEUA 013/2016): one with a THC/CBD ratio greater than 1 (XT-THC) and another with a THC/CBD ratio less than 1 (XT-CBD). The animals were treated intraperitoneally (ip) with the substances and thirty minutes later, SE was induced by intrahippocampal pilocarpine administration, behavioral parameters were quantified such as proportion of animals, seizure latency, SE duration and Racine’s scale. Open field exploration served as an indicator of the degree of sedation induced by extracts. XT-THC (doses of 1, 10, 100, 450 and 1000 mg/kg; ip; n = 6-9/group) at the two highest doses decreases seizure severity compared to vehicle (corn oil solution sterile, 10 mL/kg; ip; n = 22; p < 0.05; Mann-Whitney test), while the dose of 10 mg/kg (ip; n = 7) increased the proportion of animals that presented severe seizure behaviors. In the Racine’s scale, the dose that produces 50% of the maximum effect (ED₅₀) was 436 mg/kg. Importantly, the decrease in SE severity at the XT-THC highest dose was similar to observed in the diazepam-treated group (5 mg/kg; ip; n = 6; p > 0.05; Mann-Whitney test) and this dose also reduces the animal ambulation in open field. XT-CBD reduced SE duration and Racine’s scale at all doses evaluated (3.6; 35.8 and 358.8 mg/kg; ip; n = 6-9; p<0.05; Kruskal-Wallis test). It also decreased the ambulation in open field arena and the ED₅₀ on the Racine scale for XT-CBD was 3.46 mg/kg, therefore, more potent than XT-THC. The CBD salt given at the same doses found in the extracts did not reduce the severity of SE. Curiously, treatment with XT-THC and XT-CBD did not alter SE electrographic expression. Our results demonstrate that the anticonvulsant activity of XT-CBD and XT-THC are different, being the first bioactive from low doses and that CBD salt in the experimental conditions evaluated does not modify pilocarpine-induced SE.

BANKING MEMBERS:
Presidente - 1728817 - CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
Interno - 1698305 - RODRIGO NEVES ROMCY PEREIRA
Interno - 1660044 - SIDARTA TOLLENDAL GOMES RIBEIRO