Effect of cyclosporin A on the content of glutathione in the brain of the rat.
The effect of cyclosporin A on the content of glutathione was investigated in various regions of the brain of male Sprague-Dawley rats, weighing 275-300 g each. Treatment of rats with cyclosporin A (120 micrograms/kg/day, i.p.) resulted in approximately 50% decrease in the content of glutathione of the cerebellum within 1 hr, relative to time-matched controls, treated with olive oil vehicle. During the same period, cyclosporin A also caused an apparent, but statistically insignificant, decrease in the content of glutathione of the hypothalamus (37%), pontine nucleus (37%) and medulla oblongata (10%) and had no apparent effect on that of the cerebral cortex and the caudate nucleus. Within 24 hr of a single treatment, the content of glutathione of the rats treated with cyclosporin A returned to the control concentrations in all the regions of the brain. After 7 days of daily treatment with cyclosporin A, the content of glutathione of the hypothalamus remained within control levels, whereas that of the pontine nucleus showed an apparent decrease (30%) and those of the medulla oblongata and cerebellum decreased significantly, again by 58% and 64%, respectively, relative to their controls. This selective depletion of the content of glutathione in brain may contribute to some of the neurological side effects of cyclosporin A.
Duruibe
V A
VA
Clinical Pharmacology Research Unit, Florida A&M University, Miami.
Blyden
G T
GT
Okonmah
A
A
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003524:Cyclosporins / Q000494:pharmacology*; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D003524:Cyclosporins; D005978:Glutathione