Doxycycline protects against pilocarpine-induced convulsions in rats, through its antioxidant effect and modulation of brain amino acids

This work evaluated doxycycline (2nd generation tetracycline) protection against pilocarpine-induced convulsions in rats. The animals were treated with doxycycline (Dox: 10 to100 mg/kg, i.p., 7 days), 30 min before the pilocarpine injection (P: 300 mg/kg, i.p.) and observed for cholinergic signs, latencies to the first convulsion and death. Amino acid concentrations, lipid peroxidation and nitrite levels in temporal cortices were determined as well as the radical scavenging activity. Doxycycline increased latencies to the first convulsion and death as compared to the untreated P300 group. It also decreased glutamate and aspartate, increased GABA, blocked nitrite formation, reduced TBARS contents and showed a radical scavenging activity. Finally, doxycycline decreased the number of degenerating neurons (evaluated by fluoro-jade staining) and increased the number of viable neurons (assessed by cresyl violet staining) as compared do the P300 group. The antioxidant effect associated with decreased levels of excitatory and increased levels of inhibitory amino acids could explain the neuroprotective effect of doxycycline.

Research Highlights
► We demonstrated that doxycycline, a second generation tetracycline, increased both latency to first convulsion and latency to death in the model of pilocarpine-induced convulsions in rats.
► The mechanism of action seems to be mediated by the decrease in excitatory amino acids, such as glutamate and aspartate, and by the increase in inhibitory amino acids, mainly GABA.
► Additionally, doxycycline by its antioxidant effect could antagonize the increase of free radicals, lipid peroxidation and glutamate excitotoxicity.