J. Douglas Bricker

The effects of glutathione and vitamin E on iron toxicity in isolated rat hepatocytes.

This study examined the acute toxicity of ferrous sulfate on rat hepatocyte suspensions, the correlation between lipid peroxidation and cell death, and the roles of glutathione and vitamin E in protecting against iron toxicity. Incubation with ferrous sulfate for 2 h produced lipid peroxidation, but did not decrease cell viability in the hepatocytes. When diethyl maleate (DEM) was added to deplete cellular glutathione concentrations, ferrous sulfate treatment (2.0-5.0 mM) did cause cell death and lipid peroxidation developed more extensively, suggesting that iron-mediated hepatotoxicity is influenced by glutathione content. Reduced glutathione (GSH), N-acetylcysteine (NAC) and alpha-tocopherol (vitamin E), alone and in combination, were added to hepatocyte suspensions in an attempt to protect cells against iron-induced damage. In iron-DEM-treated cells, GSH and NAC treatment increased viability by 43 and 36%, respectively, but only the combination of the two agents reduced lipid peroxidation (53% decrease). Vitamin E treatment reduced lipid peroxidation by 39% and also increased cell viability by 12%. The greatest protection against iron-induced lipid peroxidation occurred with the combination of GSH, NAC and vitamin E, which reduced lipid peroxidation by 94% in iron-treated cells, and by 98% in iron-DEM-treated cells. However, this combination did not prevent iron-induced cell death, although it did increase viability by 18%. These results suggest that iron-induced cell death may not be dependent upon lipid peroxidation, at least in short-term exposures. The results also suggest an interaction between GSH and vitamin E in protecting against lipid peroxidation.

A death due to ethchlorvynol abuse. A case report.

Abstract A fatal case of ethchlorvynol abuse is reported with blood and tissue determinations.

SUPPRESSION OF SPLENIC T LYMPHOCYTE PROLIFERATION BY ACUTE COCAINE ADMINISTRATION

We have recently demonstrated that cocaine administration has a limited effect on mitogen-stimulated T lymphocyte proliferation. The present study investigated the effect of cocaine on splenic T cell response to alloantigens. Rats received intraperitoneal injections of cocaine HCI, and splenocytes were isolated either thirty minutes or three hours post-administration. In the thirty minute exposure group, cocaine at 10.0 and 25.0 mg/Kg/B.Wt. suppressed (p<0.05) T cell proliferation in mixed lymphocyte cultures. Compared to control data, proliferation was decreased by 46.6% and 56.4%, respectively. However, this effect was not as pronounced in cells isolated three hours post-administration, indicating a transient inhibition of T cell function by cocaine. The decrease in splenic T cell proliferation in response to alloantigens in the thirty minute exposure group did not reflect alterations in calcium influx or IL-2 production. Although this study did not ascertain the exact mechanism of inhibition, these results demonstrate that short-term cocaine exposure can alter T cell reactivity to alloantigens, suggesting a reduction in the functional status of these cells.

Effect of cocaine administration on concanavalin A-stimulated T-lymphocyte proliferation in rats

There is a high prevalence of cocaine abuse among Americans. There is an increasing concern over the rise of infectious diseases among individuals in this drug abuse population. This concern may be due, at least in part, to a direct effect of cocaine on the immune system. The present study investigated the effects of cocaine administration on optimal mitogen-induced proliferation in rats. Following cocaine administration, splenic lymphocytes were isolated and T-lymphocytes incubated with concanavalin A. When T-lymphocytes were isolated 30 minutes following cocaine administration, a significant enhancement of optimal mitogen-stimulated proliferation was observed at 0.1 mg/Kg cocaine. Enhancement of proliferation was seen 20 hours following cocaine administration at 0.1, 1.0 and 10 mg/Kg. However, these results were not statistically significant. Cocaine administered once daily for seven days had no effect on mitogen-induced proliferation. These results suggest that cocaine administration has a limited effect on optimal mitogen-stimulated proliferation.