Neurochemical changes of doxycycline in rat striatal submitted to model of temporal lobe epilepsy induced by the pilocarpine

I.B.F. Calou1, R.M.P. Siqueira1, A.L.C. Cavalcante2, T.M. Olinda1, D.O. Gonçalves1, K.R.T. Neves1, G.S. Cerqueira1, F.A.V. Lima1, G.S.B. Viana1. 1Federal University of Ceara, Physiology and Pharmacology 60430270, Brazil, 2Federal University of Ceara, Medicine 60430140, Brazil

Objective: To assess the neurochemical effects of administration of doxycycline in animal model of temporal lobe epilepsy induced by pilocarpine.

Methods: We used male Wistar rats (200-250g, n=6), divided into four groups N (animals treated with saline), P400 (animals treated with pilocarpine 400mg/Kg i.p.), D25 and D50 (animals pretreated with doxycycline 25 e 50mg/Kg p.o.) after one hour treated with pilocarpine 400 mg/Kg i.p. (groups: P400, D25 and D50) or saline i.p. (group: N) and after three hours of induced seizures, the animals were decapitated and their brains dissected. The striatum was removed and the homogenate prepared in 10% perchloric acid to 1%. For this dosing device was used for high performance liquid chromatography (HPLC). Before administering the standard sample was applied in micro concentration of 2.5 µM (aspartate, glutamate, glycine, taurine, and GABA). Statistical analysis by ANOVA followed by Student-Newman-Keuls test with p <0.05.

Results: The reduced levels of aspartate in P400 (7.33 ± 1.39 µmol/g of tissue) and D25 and D50 (3.82 ± 1.04 and 3.78 ± 1.86 µmol/g tissue) compared to N group (10.62 ± 3.49 µmol/g of tissue). Glutamate levels were higher in group P400 (4.63 ± 1.48 µmol/g tissue) and D50 (4.75 ± 0.96 µmol/g of tissue) compared with the group N (2.29 ± 1.15 µmol/g of tissue), no significant difference in D25. Glycine levels were elevated in P400 (12.67 ± 4.34 µmol/g of tissue) and D25 and D50 (25.13 ± 3.95 µmol/g tissue and 33.55 ± 5.69 µmol/g tissue) compared with the group N (6.22 ± 4.42 µmol/g tissue). The increased levels of taurine in P400 (8.36 ± 2.15 µmol/g of tissue) compared with the group N (4.94 ± 2.57 µmol/g of tissue) and converted into D25 (5.28 ± 1.00 μmol/g tissue) with no significant difference in D50. GABA levels increased P400 (17.72 ± 2.63 µmol/g of tissue) and D25 and D50 (11.35 ± 1.63 and 17.15 ± 3.37 µmol/g of tissue) compared to N group (4.52 ± 1.36 µmol/g tissue).

CONCLUSION: Doxycycline showed promote changes in the levels of inhibitory and excitatory amino acids in striatum of rats submitted to pilocarpine-induced seizure. These changes are significant for understanding the neuroprotective activity of doxycycline in this seizure model.