Disposition of Cocaine and Norcocaine in Blood and Tissues of B6C3F1 Mice

Kump, Denton F.; Matulka, Ray A.; Edinboro, Leslie E.; Poklis, Alphonse; Holsapple, Michael P.

doi:10.1093/jat/18.6.342

Cited by 10 publications

(2 citation statements)

References 4 publications

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“…Cocaine has been detected in the thymus of cocaineinjected mice (16). In this report, we demonstrated that the ability of the cells from cocaine-injected mice to survive in culture was reduced inversely proportional to the amount of cocaine injected (Table 11).…”

Section: Discussionmentioning

confidence: 58%

The Effects of Cocaine Injections on Mouse Thymocyte Population

Shen

et al. 1997

Experimental Biology and Medicine

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C57 BL mice were injected daily with either saline or varied doses of cocaine (5-50 mg/kg), and thymocyte subpopulations were analyzed 4 hr after the fifth injection. Mice injected with either 25 or 50 mg/kg of cocaine showed a decrease in the percentage of CD4+8+ cells and increase of CD4-8-, CD4+, and CD8+ cells. The absolute numbers of each subpopulation, calculated by multiplying the percentage of each subpopulation with the total cell number, revealed an extensive decline in CD4+8+, a decrease in CD8+, an increase in CD4-8-, and no change in the CD4+ subpopulation. Flow cytometric analysis of thymocytes and electrophoresis of the thymocyte DNA revealed a dosage-dependent increase in cells undergoing programed cell death with apoptosis. Culturing of thymocytes from control or drug-treated mice demonstrated an inverse relationship between cell viability and cocaine concentrations, suggesting that in vivo cocaine, or its biological products, may damage thymocytes. Incubation of normal cells with cocaine showed a dose-dependent decrease of viability with identical patterns of the alteration of cell subpopulations observed in vivo. A dose-dependent increase of apoptosis was also observed. In summary, we demonstrate a selective in vivo cocaine-induced alteration of the thymocyte subpopulations and identified programed cell death with apoptosis as the likely mechanism mediating this thymic atrophy. The comparable findings observed in vivo and in vitro support the concept that cocaine may directly affect some features of thymocyte biology, and suggest the usefulness of the in vitro system in studying cocaine effects on thymocyte biology.

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Section: Discussionmentioning

confidence: 58%

The Effects of Cocaine Injections on Mouse Thymocyte Population

Shen

et al. 1997

Experimental Biology and Medicine

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“…Moreover, reports of cocaine-related deaths have shown postmortem blood levels ranging from 1 µM to 1 mM (Karch et al 1998;Mackey-Bojack et al 2000). In general, the organ concentrations of cocaine are higher than those in the blood, with maximum concentrations typically found in the brain, lungs, liver, spleen, and kidneys (Amoedo et al 1999;Kump et al 1994;Poklis et al 1987). Collectively, these studies suggest that the physiological relevance of the ndings of the present study, which show that hepatocellular necroptosis occurs via cocaine-induced in ammation, is reasonable.…”

Section: Discussionmentioning

confidence: 99%