PMID: 3765053Oct 1, 1986Paper

A comparative toxicological study of cyclosporine and Nva2-cyclosporine in Sprague-Dawley rats

Transplantation
J I DuncanP H Whiting

Abstract

Adult, male Sprague-Dawley rats were given 50 mg/kg cyclosporine (CsA), cyclosporine G (nor-valine2-cyclosporine [CsG], or drug vehicle by orogastric intubation every 24 hr for 14 days. Both drugs profoundly suppressed humoral immune responses. Similar trough whole-blood cyclosporine levels were recorded in each group at days 7 and 14. In CsA-treated animals, significant lymphopenia was evident on day 14, together with monocytosis and neutrophilia. Only the monocytosis was seen in the CsG group. CsA and CsG both caused significant impairment of renal function by day 7, although at this time the effect was less marked with CsG. In both drug-treated groups, there was evidence of further deterioration in glomerular filtration rate (GFR) by day 14. A significant rise in enzymuria was also recorded in each group. Typical cyclosporine-induced proximal straight tubular cell vacuolation was evident in four of the eight rats given CsG and in three of seven CsA-treated animals. Liver function was also significantly impaired in both CsA and CsG groups. These data show that, at the selected dose, CsG shares the nephrotoxic and hepatotoxic properties of CsA. The extent to which these effects of CsG are dose-related and the true clinical pot...Continue Reading

Citations

Apr 1, 1988·Transplant International : Official Journal of the European Society for Organ Transplantation·M A MasriA S Daar
Mar 26, 2004·Transplantation Proceedings·J J Curtis
Nov 1, 1988·Toxicology and Applied Pharmacology·U A BoelsterliP Donatsch
Jan 22, 2003·Xenotransplantation·F CicchettiO Isacson

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