Protective effect of phenytoin and its enhanced action by combined administration with mannitol and vitamin E in cerebral ischaemia

Abstract

To study the therapeutic effect of phenytoin on cerebral ischaemia and confirm whether or not the effectiveness of phenytoin could be enhanced by combined administration with free radical scavengers, twenty-five dogs were subjected to ischaemia, using the "canine model of the completely ischaemic brain regulated with a perfusion method". Five animals served as untreated controls, fifteen received treatment with several doses of phenytoin and five were treated with 10 mg/kg phenytoin, 2 g/kg mannitol and 30 mg/kg vitamin E. These drugs were administered prior to the production of ischaemia. After one hour ischaemia, cerebral blood flow was restored and the recovery of electrical activity of the brain and the degree of brain swelling were observed for three hours. With regard to the recovery of the EEG, the higher the administered dosage, the better was the degree of recovery of the EEG. And the group which was treated with a combination of phenytoin, mannitol and vitamin E exhibited remarkable recovery of the EEG. With regard to the degree of brain swelling, a similar dose-related suppressive effect was seen in the phenytoin-treated groups. Furthermore, in the combination therapy group, brain swelling was attenuated significantly. Based on these results, it is concluded that phenytoin has a protective effect in cerebral ischaemia and it shows its most remarkable effect when given together with radical scavengers, such as mannitol and vitamin E.

Phenytoin protected mouse cortical cell cultures against neurotoxicity induced by kainate but not by NMDA

“…The protective effect of PHT against ischemic brain damage (Cullen et al, 1979;Fukuda et al, 1983;Suzuki et al, 1987) and kainate-induced neurotoxicity (Zaczek et al, 1978) in vivo agreed with our present results. No protective effect of PHT was found against glutamateinduced neurotoxicity in cortical cell culture (Koh and Choi, 1987a).…”

“…Also, PHT is indicated to block glutamate receptors (Matthews and Connor, 1977;Sastry and Phillis, 1976) though there have been conflicting reports (McLean and Macdonald, 1983;Nicoll and Wojtowicz, 1980). Several investigators reported that PHT protected the neurons of dogs (Suzuki et al, 1987) and rabbits (Cullen et al, 1979) against cerebral ischemia. However, they did not consider PHT as a glutamate blocker probably because the PHT blockage of glutamate receptors had been doubtful.…”

Effect of methylprednisolone, tirilazad mesylate and vitamin E on lipid peroxidation after experimental spinal cord injury

“…The doses of TM, MP and vitamin E were selected on the basis of previous studies. 13,47,48 Our experimental study demonstrated that all three treatment regimens decreased the level of LP following spinal cord trauma in rats. Vitamin E was less e ective than TM and MP.…”

The efficacy of antioxidants in functional recovery of spinal cord injured rats: an experimental study

“…A variety of other approaches to protect the injured spinal cord from secondary pathological processes have been examined experimentally, including antioxidants, membrane stabilizers, glutamate antagonists, anti-inflammatories, caspase inhibitors, calpain inhibitors and other compounds of uncertain mechanism [15]. During the past decade, considerable research efforts have been focused on the role of free radicals in the occurrence of ischemic damage [16,17]. In this study, ascorbic acid and alphatocopherol known as free radical scavengers were used to investigate their efficacy in the functional recovery of spinal cord injured rats.…”