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The effects of oral cyclosporin A (25 mg/kg/day) on renal function and structure in groups of normal, laparotomized and unilaterally nephrectomized DA rats was assessed over a 4-week period. In each group, the drug caused impairment of function, although there was evidence of improvement during the course of the study. Cyclosporin A toxicity was most marked in the nephrectomized animals, where histological examination at 4 weeks revealed extensive damage to proximal straight tubular cells. Only minimal structural damage was observed in the two other groups. Cyclosporin A concentrations in whole blood and kidney were estimated by radioimmunoassay at 4 weeks. Similar drug levels were found in normal, laparotomized and nephrectomized animals, except for an unexplained fall in blood levels in the laparotomy group. The significance of these observations is discussed in the context of current knowledge concerning the physiological effects, toxicology and pharmacology of cyclosporin A.
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