Developmental immunotoxicity of cocaine and ethanol in postnatal Lewis rats

Figliomeni, Maria L.; Turkall, Rita M.

doi:10.1016/s0162-3109(96)00153-1

Cited by 10 publications

(2 citation statements)

References 32 publications

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“…Lewis rats are strains frequently employed in the testing of the autoimmune effect of xenobiotics. Recently, Lewis rats were used for testing the immunotoxic effects of chemicals such as cocaine and ethanol 19 and the virus host resistance in animals given morphine. 20 In contrast to Descotes et al 21 and Richter-Reichhelm and Schulte, 18 who found a low thymus weight in Wistar rats, no alterations in thymus weight were observed either in the ICICIS study 16 or in our Lewis rats.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…For example, the exposure of rat pups to di-n-octyltin dichloride during the first 3 weeks of life resulted in suppression of the PHA response, which persisted up to 10 weeks of age (160). Rat pups exposed to cocaine from postnatal day 1-21 had decreased peripheral blood lymphocytes on day 22, whereas pups exposed to both cocaine and ethanol had decreased total IgM levels (161). Weanling (i.e., 25-day-old) rats dosed 4 times over 17 days with 3,3',4,4'-tetrachloroazoxybenzene had reduced thymus weights, antibody responses to SRBC, peritoneal macrophage chemiluminescence, and bone marrow cellularity.…”

Section: Postatal Immunotoxicant Exposurementioning

confidence: 99%

Development of the murine and human immune system: differential effects of immunotoxicants depend on time of exposure.

Holladay

Smialowicz

2000

Environ Health Perspect

236

177

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Fetal and early postnatal life represent critical periods in vertebrate immune system development. Disruption of such development by perinatal immunotoxic chemical exposure has been widely described in experimental animal models. The resultant inhibited postnatal immune responses in such animals are often more dramatic and persistent than those after exposure during adult life. Further, recent reports suggest that prenatal exposure to immunotoxicants may exacerbate postnatal aberrant immune responses (e.g., hypersensitivity disorders and autoimmune disease) in genetically predisposed rodents. Limited information is available regarding the possibility of inhibited postnatal immune capacity in humans as a result of developmental immunotoxicant exposure. The multifactorial nature of hypersensitivity and autoimmune responses will further complicate the elucidation of possible relationships between chemical exposure during ontogeny of the human immune system and immune-mediated disease later in life. Taken together, however, the available animal data suggest the potential for altered postnatal immune function in humans exposed to immunotoxicants (e.g., environmental chemicals and therapeutic agents) during fetal and/or early postnatal life.

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