CsA-induced Toxicity Research Articles

Nifedipine Protects Small Intestine from Cyclosporine-Induced Hemodynamic and Functional Impairment

We have previously shown that cyclosporine (CsA) causes intestinal hemodynamic and functional impairments. In this study, we evaluated whether nifedipine protects the small intestine from such toxic side effects. Isogeneic small intestinal transplantation was performed in rats which then received one of the following two-week treatments: olive oil, 0.15 ml/kg/day i.m. as vehicle controls in group 1; nifedipine, 1 mg/kg/day i.m. in group 2; CsA, 15 mg/kg/day i.m. in group 3; and both nifedipine and CsA in group 4. Vascular resistance, whole tissue blood flow and its mucosal and serosal/muscularis distributions in both graft and recipient residual native intestines, and absorptive function were determined. The data showed that two-week treatment with CsA resulted in a marked elevation of vascular resistance from 51.0 ± 6.8 to 72.4 ± 11.1 U/g in the native whole tissue and from 53.7 ± 7.2 to 78.2 ± 12.1 U/g in the graft whole tissue, and decreases in blood flow from 1.59 ± 0.26 to 1.11 ± 0.17 ml/g/min in the native whole tissue and from 1.50 ± 0.21 to 1.03 ± 0.18 ml/g/min in the graft whole tissue and absorption from 227 ± 36 to 166 ± 26 mg glucose/dl. Mucosa was preferentially affected, while serosal/muscularis layers remained relatively unchanged. When nifedipine was concomitantly used with CsA, vascular resistance and blood flow values in the mucosal layer and whole intestinal tissue as well as absorptive function showed no significant differences from the baseline data. The changes observed in denervated grafts and recipient native intestines were similar. We conclude that nifedipine is effective in protecting both graft and native small intestines from CsA-induced toxicity in the rat.