Role of metabolism in cocaine-induced immunosuppression in splenocyte cultures from B6C3F1 female mice

Jeong, Tae Cheon; Matulka, Ray A.; Jordan, Stephen D.; Yang, Kailun; Holsapple, Michael P.

doi:10.1016/0162-3109(95)00042-r

Cited by 10 publications

(5 citation statements)

References 32 publications

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“…suppression is only exhibited with a high concentration of NC (Jeong et al 1995b). Further, inhibition of oxidative metabolism by SKF-525A pretreatment had no effect on the splenic or thymic histopathological changes produced by COC alone.…”

Section: Figurementioning

confidence: 99%

Effect of Ketamine on Cocaine-Induced Immunotoxicity in Rats

2003

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The abuse of cocaine (COC) with ketamine (KET) is currently popular among young drug abusers and has been associated with increased risk of human immunodeficiency virus (HIV) infection. The effect of subacute exposure to COC and KET alone and in combination on the immune system was assessed in adult male Sprague-Dawley (SD) rats. To simulate the route and mode of human exposure, rats were treated with COC alone (5 mg/kg, i.v.), KET alone (100 mg/kg, p.o.) or KET followed immediately by COC (same doses and routes of administration) once-a-day for 7 consecutive days. Rats were sacrificed 30 minutes following the last treatment. Total circulating leukocyte and lymphocyte counts were decreased with relative neutrophilia, whereas immunoglobulin M (IgM) antibody response to sheep erythrocytes (SRBCs) was increased in animals treated with COC. Moreover, treatment with COC alone increased serum interleukin-10 (IL-10) concentration; however, it did not affect serum interferon gamma (INF-gamma) concentration. Spleen histology showed hyperplasia of white pulp whereas thymus gland demonstrated mild cortical degeneration. On the other hand, KET treatment did not produce any significant change of any of these parameters. However, when coadministered with COC, significant reduction of bodyweight, spleen/bodyweight, and thymus/bodyweight ratios with degeneration of splenic white pulp and thymic cortex occurred. Moreover, the primary immunoglobulin response to SRBC and serum IL-10 concentration were decreased without significant change in serum IFN-gamma or circulating leukocytic counts. COC caused a significant increase in serum corticosterone concentration that KET effectively prevented. On the other hand, a significant increase in plasma and tissue concentrations of norcocaine (NC) resulted following KET and COC administration in combination. Daily SKF-525A pretreatment at a dose of 30 mg/kg, i.p., for 7 days 1 hour prior to KET and COC in combination effectively reversed the effects of this combination on body weight, organ/bodyweight ratios, histopathology, and serum IgM and IL-10 concentrations without affecting leukocytic counts. On the other hand, SKF-525A pretreatment did not change the immunomodulatory effects of COC compared to non-pretreated animals. The results suggest that COC-induced immunomodulation most likely occurred through neuroendocrinal mechanisms. On the other hand, enhanced oxidative metabolism of COC in the presence of KET-induced immunosuppression.

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Section: Figurementioning

confidence: 99%

Effect of Ketamine on Cocaine-Induced Immunotoxicity in Rats

2003

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“…c Statistical difference versus column 7. suppression is only exhibited with a high concentration of NC (Jeong et al 1995b). Further, inhibition of oxidative metabolism by SKF-525A pretreatment had no effect on the splenic or thymic histopathological changes produced by COC alone.…”

Section: Figurementioning

confidence: 83%

“…ROS have been reported to be responsible for the immunosuppressant effects of COC on the primary antibody response (Jeong et al 1995a(Jeong et al , 1996Kump et al 1996;Matulka et al 1996). On the other hand, neither COC or BE caused suppression of the primary antibody response to SRBCs (Jeong et al 1995b). The immunosuppressive effects of ROS on serum anti-SRBC IgM appear to be mediated through direct inhibition of Th2 cells, as there was a significant reduction of serum IL-10 without change in IFN-γ .…”

Section: Figurementioning

confidence: 83%

“…Blood, liver, thymus, and spleen were obtained and immediately placed on ice. The dosage of the drugs and duration of exposure were chosen on the basis of previous reports (Di Francesco et al 1994;Jeong et al 1995b;Kump et al 1996;Rofael and Abdel-Rahman 2002a). In a separate study, adult male rats were pretreated daily for 7 consecutive days with SKF-525A (30 mg/kg, IP) followed 1 hour later by saline, COC alone, KET alone, or KET combined with COC as described above.…”

Section: Experimental Designmentioning

confidence: 99%

“…esterase inhibitors or cytochrome P-450 inducers, COC causes suppression through the production of reactive intermediates formed through P-450 oxidative metabolism (Holsapple 1995;Jeong et al 1995aJeong et al , 1995bJeong et al , 1996Kump et al 1996;Matulka et al 1996). However, at lower doses (20 to 30 mg/kg, IP), COC potentiates immunoglobulin M (IgM) antibody response to sheep red blood cells (SRBCs), an effect that is mediated through the production of corticosterone via stimulated hypothalamic-pituitaryadrenal (HPA) axis (Stanulis et al 1997b).…”

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confidence: 99%

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Effect of Ketamine on Cocaine-Induced Immunotoxicity in Rats

Rofael¹,

Turkall²,

Abdel-Rahman³

2003

UITO

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The abuse of cocaine (COC) with ketamine (KET) is currently popular among young drug abusers and has been associated with increased risk of human immunodeficiency virus (HIV) infection. The effect of subacute exposure to COC and KET alone and in combination on the immune system was assessed in adult male Sprague-Dawley (SD) rats. To simulate the route and mode of human exposure, rats were treated with COC alone (5 mg/kg, IV), KET alone (100 mg/kg, PO) or KET followed immediately by COC (same doses and routes of administration) once-a-day for 7 consecutive days. Rats were sacrified 30 minutes following the last treatment. Total circulating leukocyte and lymphocyte counts were decreased with relative neutrophilia, whereas immunoglobulin M (IgM) antibody response to sheep erythrocytes (SRBCs) was increased in animals treated with COC. Moreover, treatment with COC alone increased serum interleukin-10 (IL-10) concentration; however, it did not affect serum interferon gamma (INF-γ) concentration. Spleen histology showed hyperplasia of white pulp whereas thymus gland demonstrated mild cortical degeneration. On the other hand, KET treatment did not produce any significant change of any of these parameters. However, when coadministered with COC, significant reduction of bodyweight, spleen/bodyweight, and thymus/bodyweight ratios with degeneration of splenic white pulp and thymic cortex occurred. Moreover, the primary immunoglobulin response to SRBC and serum IL-10 concentration were decreased without significant change in serum IFN-γ or circulating leukocytic counts. COC caused a significant increase in serum corticosterone concentration that KET effectively prevented. On the other hand, a significant increase in plasma and tissue concentrations of norcocaine (NC) resulted following KET and COC administration in combination. Daily SKF-525A pretreatment at a dose of 30 mg/kg, IP, for 7 days 1 hour prior to KET and COC in combination effectively reversed the effects of this combination on body weight, organ/bodyweight ratios, histopathology, and serum IgM and IL-10 concentrations without affecting leukocytic counts. On the other hand, SKF-525A pretreatment did not change the

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Human‐Based In Vitro Experimental Approaches for the Evaluation of Metabolism‐Dependent Drug Toxicity

2021

Transporters and Drug‐Metabolizing Enzymes in Drug Toxicity

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Role of metabolism in cocaine-induced immunosuppression in splenocyte cultures from B6C3F1 female mice

Cited by 10 publications

References 32 publications

Effect of Ketamine on Cocaine-Induced Immunotoxicity in Rats

Effect of Ketamine on Cocaine-Induced Immunotoxicity in Rats

Effect of Ketamine on Cocaine-Induced Immunotoxicity in Rats

Human‐Based In Vitro Experimental Approaches for the Evaluation of Metabolism‐Dependent Drug Toxicity

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