Immune parameters are affected differently after cyclosporine A exposure in Fischer 344 rats and B6C3F1 mice: implications for immunotoxicology

Blot, Christian; Lebrec, Hervé; Roger, R. Beerli; Bohuon, R.; Pallardy, Marc

doi:10.1016/0300-483x(94)90041-8

Cited by 10 publications

(11 citation statements)

References 17 publications

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“…Similar results of unaffected body weight were observed in several rodent studies with CsA [27][28][29][30]56]. However, in other studies, reduction in body weight was observed, varying between laboratories and varying with sex [29,31,39].…”

Section: Effects On Growth Organ Weights and Histopathologysupporting

confidence: 85%

“…CsA-treatment showed only minor effects on NK cell activity of PBMC isolated from minipigs, which is in line with the lack of effect on NK cell activity in a placebo controlled study in human subjects with insulin-dependent diabetes mellitus type I [38]. In several observations made in rodents treated with CsA, either no effect [27,31,39,40] or a tendency to increased NK activity was observed [29,30,41]. Interestingly, in studies of Blot et al [27], it was observed that in splenic cells of mice but not of rats NK cell activity was dosedependently decreased upon exposure to comparable dose levels of CsA even though the blood concentrations of CsA were higher in the rat than in the mouse.…”

Section: Nk Cell Activity Assaysupporting

confidence: 77%

“…Statistically significant decreased proliferative responses of PBMC to ConA stimulation were observed for both the CsA-and DEX-treated minipigs on day 27. Published studies in rodents treated with CsA demonstrate non-consistent results either showing no effect [45] or a reduced [27,30,31,39] splenocyte proliferation after ConA stimulation. In humans treated with CsA, either no effect [38] or a decreased [46] mitogeninduced proliferation has been observed.…”

Section: Proliferation Assaymentioning

confidence: 92%

“…In several observations made in rodents treated with CsA, either no effect [27,31,39,40] or a tendency to increased NK activity was observed [29,30,41]. Interestingly, in studies of Blot et al [27], it was observed that in splenic cells of mice but not of rats NK cell activity was dosedependently decreased upon exposure to comparable dose levels of CsA even though the blood concentrations of CsA were higher in the rat than in the mouse. A clear but not significant decrease in NK activity was observed after DEX treatment in minipigs.…”

Section: Nk Cell Activity Assaymentioning

confidence: 95%

“…Decreased WBC and lymphocyte counts are observed in rodents after CsA treatment also, dependent on the dose [27][28][29][30][31]. Rhesus monkeys showed a transient decrease of leukocyte counts at higher doses of CsA (≥60 mg/kg/day) and in dogs at 45 mg CsA/kg/ day a slight decrease in leukocyte counts was observed as well [32].…”

Section: Hematologymentioning

confidence: 99%

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A Sub Acute Immunotoxicity Study in G?ttingen Minipigs? with the Immunosuppressive Compounds Cyclosporin A and Dexamethasone

2013

Clin Exp Pharmacol

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Introduction: There is a growing interest in the minipig as a non-rodent species in the safety assessment of (bio) pharmaceuticals and (agro) chemicals. For (bio) pharmaceuticals the need to evaluate the potential adverse effects on the immune system is an increasingly important aspect of safety evaluation. In the present study, cyclosporin A and Dexamethasone were used as model compounds to examine whether the regulatory endpoints requested for immunotoxicity testing can be tested in the Göttingen minipig.

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Section: Effects On Growth Organ Weights and Histopathologysupporting

confidence: 85%

Section: Nk Cell Activity Assaysupporting

confidence: 77%

Section: Proliferation Assaymentioning

confidence: 92%

Section: Nk Cell Activity Assaymentioning

confidence: 95%

Section: Hematologymentioning

confidence: 99%

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A Sub Acute Immunotoxicity Study in G?ttingen Minipigs? with the Immunosuppressive Compounds Cyclosporin A and Dexamethasone

2013

Clin Exp Pharmacol

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Effect of cyclosporin A in Lewis rats in vivo and HeLa cells in vitro

Sovcikova

Tulinská

Kubová

et al. 2002

J of Applied Toxicology

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The aim of this study was to compare the effect of cyclosporin A (CsA) in inbred Lewis rats with published assessment of immunotoxicity in 'classical' outbred Wistar rats. A second purpose was to consider the contribution of a panel of in vitro assays in cell cultures when added to an immunotoxicity study in vivo. The in vivo effect of CsA was investigated in a 28-day subacute immunotoxicity study in male Lewis rats at three different concentrations: 1.25, 5 and 20 mg kg(-1). The highest dose of CsA exceeded the maximum tolerated dose. A drop in body, spleen and popliteal lymph node weight of exposed animals displayed symptoms of toxicity. At a high toxic dose, haematological changes showed a decrease in the leucocyte count and in the percentage of lymphocytes, and an increase in the percentage of polymorphonuclear leucocytes. The haematocrit was significantly dose-dependently suppressed in all rats exposed to CsA. A similar dose-dependent depression of the mean cell volume of erythrocytes was found in rats given high and middle doses of CsA. The phagocytic activity of polymorphonuclear leucocytes and monocytes also was significantly dose-dependently suppressed. No significant changes in primary antibody response to sheep erythrocytes or in vitro proliferative response of spleen lymphocytes to mitogens were found in those rats.A battery of in vitro cytotoxicity methods was selected for the evaluation of metabolic and functional activity of subcellular organelles (mitochondria, lysosomes) and for the detection of drug-induced superoxide-mediated damage in HeLa cells. This cell line was chosen because it has a lower activity of superoxide dismutase (SOD) than normal cells and is sufficiently sensitive for the detection of the induction of oxygen radicals. The in vitro results indicated a direct relationship between CsA cytotoxicity and a change in the mitochondrial enzyme activity, as well as an induction of superoxide production. The results of the study indicated that a combination of selected in vivo and in vitro methods is an inexpensive way to obtain more complex information on cell status affected by xenobiotics.

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Natural Killer Cells*

Campbell¹,

Carayannopoulos²

2010

Comprehensive Toxicology

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Immune parameters are affected differently after cyclosporine A exposure in Fischer 344 rats and B6C3F1 mice: implications for immunotoxicology

Cited by 10 publications

References 17 publications

A Sub Acute Immunotoxicity Study in G?ttingen Minipigs? with the Immunosuppressive Compounds Cyclosporin A and Dexamethasone

A Sub Acute Immunotoxicity Study in G?ttingen Minipigs? with the Immunosuppressive Compounds Cyclosporin A and Dexamethasone

Effect of cyclosporin A in Lewis rats in vivo and HeLa cells in vitro

Natural Killer Cells*

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