Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Cel. Nunes de Melo, 1127, CEP 60430-270, Fortaleza, Brazil.
Pharmacol Biochem Behav. 2011 Jun;98(4):525-32. doi: 10.1016/j.pbb.2011.02.025. Epub 2011 Mar 5.
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., 7days), 30min before the pilocarpine injection (P: 300mg/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.
本研究评估了强力霉素（第二代四环素）对匹罗卡品诱导的大鼠惊厥的保护作用。动物在匹罗卡品注射前 7 天用强力霉素（Dox：10 至 100mg/kg，腹腔注射）处理，观察胆碱能症状、第一次惊厥和死亡的潜伏期。还测定了颞皮质中的氨基酸浓度、脂质过氧化和亚硝酸盐水平以及自由基清除活性。与未经处理的 P300 组相比，强力霉素增加了第一次惊厥和死亡的潜伏期。它还降低了谷氨酸和天冬氨酸，增加了 GABA，阻断了亚硝酸盐的形成，降低了 TBARS 含量，并表现出自由基清除活性。最后，与 P300 组相比，强力霉素减少了变性神经元的数量（通过荧光褐素染色评估）并增加了存活神经元的数量（通过 Cresyl Violet 染色评估）。与兴奋性氨基酸水平降低和抑制性氨基酸水平升高相关的抗氧化作用可能解释了强力霉素的神经保护作用。
