Therapeutic potential of treatment with the flavonoid rutin after cortical focal ischemia in rats.
Flavonoids have known anti-inflammatory and antioxidative actions, and they have been described as neuroprotective and able to reduce damage in CNS diseases. We evaluated the action of the flavonoid rutin in an animal model of focal cortical ischemia induced by unilateral thermocoagulation of superficial blood vessels of motor (M1) and somatosensory (S1) primary cortices. Ischemic rats were submitted to daily injections (i.p.) for five days, starting immediately after induction of ischemia. We tested two doses: 50mg/kg or 100mg/kg of body weight. Sensorimotor tests were used to evaluate functional recovery. Bioavailability in plasma was done by chromatographic analysis. The effect of treatment in lesion volume and neurodegeneration was evaluated 48 h and 72 h after ischemia, respectively. We observed significant sensorimotor recovery induced by rutin, and the dose of 50mg/kg had more pronounced effect. Thus, this dose was used in further analyses. Plasma availability of rutin was detected from 2h to at least 8h after ischemia. The treatment did not result in reduction of lesion volume but reduced the number of degenerated neurons at the periphery of the lesion. The results suggest rutin as an efficient drug to treat brain ischemia since it was able to promote significant recovery of sensorimotor loss, which was correlated to the reduction of neurodegeneration in the periphery of cortical injury. Increasing studies with rutin and other flavonoids might give support for further clinical trials with these drugs.
Laboratório de Biologia Celular e Tecidual, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF), Campos dos Goytacazes, RJ, Brazil.
Amélia Miranda Gomes
AM
Rodrigues
Fralini Dos Santos
Fdos S
Marcilio
Michelle
M
Frazão Muzitano
Arthur
A
Giraldi-Guimarães
D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins; D008297:Male; D053580:Muscle Strength / Q000187:drug effects; D018696:Neuroprotective Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D012431:Rutin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
D005452:Fluoresceins; D018696:Neuroprotective Agents; C534582:fluoro-jade C; D012431:Rutin