RESULTS OF A CYCLOSPORINE-A RINGSTUDY

Citation
Hb. Richterreichhelm et Ae. Schulte, RESULTS OF A CYCLOSPORINE-A RINGSTUDY, Toxicology, 129(1), 1998, pp. 91-94
Citations number
13
Categorie Soggetti
Toxicology,"Pharmacology & Pharmacy
Journal title
ISSN journal
0300483X
Volume
129
Issue
1
Year of publication
1998
Pages
91 - 94
Database
ISI
SICI code
0300-483X(1998)129:1<91:ROACR>2.0.ZU;2-Z
Abstract
The aim of the study was to find out whether an extended subacute toxi city study (additional organ weights, histopathology and immune functi onal tests), routinely employed in testing of chemicals, would shown i ndications of (adverse) effects on the immune system below general tox icity. Therefore, a five laboratory ring study on the basis of an oral 28-day repeated dose study in rats (OECD guideline 407) was carried o ut with 1, 5 and 25 mg/kg of cyclosporin A (CsA) per day by gavage. Be sides some toxic effects such as reduced body weight gain and increase d kidney calcification in the high-dose group, the results of the addi tional pathologic examinations revealed that CsA caused a pattern of s pecific morphological alterations of the lymphoid tissues in mid- and high-dose groups. Selected immune parameters such as immunoglobulin de termination, plaque-forming assay, flow cytometry, activation status o f macrophages and natural killer cells (NK), and proliverative respons e of spleenocytes and cells from mesenteric lymph nodes (concanvalin A (ConA) and pokeweed mitogen (PWM)stimulation) were also investigated. Some results compared to the controls revealed alterations down to th e low-dose group. The extended methodology consistently indicated the potential detection of effects on the immune system below general syst emic toxicity. The study will be continued by investigating a second c ompound with primarily immunostimulating effects. Results from those s tudies should further contribute to the current discussion of up-datin g of repeated dose toxicity guidelines with respect to immunotoxicity. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.