We studied the uroprotective effect of
mesna, at doses of 40-300 mg/kg/i.p., in single or fractioned
injections, on the development of
cyclophosphamide (CP, 100 mg/kg/i.p.)
cystitis in rats. The study concerns the histological, behavioural and nervous aspects of the disease. The specific effects of
mesna, when injected alone, have also been considered. The
mesna itself does not have specific deleterious effects, except at a dose of 300 mg/kg which provokes a moderate vesical
inflammation although without consequence on the animal's behaviour.
Mesna offers good protection against CP
cystitis for only certain posologies. The uroprotective effects of
mesna reach maxima at doses of 40-100 mg/kg and for fractioned
injections given over the entire time frame of the urinary toxic release. The uroprotective effects of other posologies are only partial. The nervous activities were studied through the expression of Fos
protein. The repetitive
intraperitoneal injection of
mesna induced a spinal activity and a preferential contralateral activity of the trigemino/reticular areas of the brainstem spinal cord junction--an effect which was reduced in the presence of CP. The prevention of
cystitis by
mesna was accompanied only by a reduction in spinal Fos activity, the supraspinal activities remaining high and in strict relationship with the vagal afferent activity. In conclusion, the uroprotective effect of
mesna, which requires appropriate posologies, has led to the confirmation of the spinal actions of the CP
cystitis, probably via the pelvic nerve, but did not allow a clear distinction between the consequences of the systemic (vagal) and local (spinal, pelvic) actions of CP at supraspinal level.