Modulation of the haematopoietic toxicity associated with zidovudine <i>in vivo</i> with lithium carbonate

Gallicchio, Vincent S.; Hughes, Nedda K.; Tse, Kam-Fai

doi:10.1111/j.1365-2796.1993.tb00985.x

Cited by 17 publications

(3 citation statements)

References 18 publications

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“…e results are in agreement with previous findings showing the selective cytotoxic effect of lithium on cancerous cells while sparing their noncancerous counterparts [24,[38][39][40]. Moreover, this work supports the reliable safe use of lithium in clinical health and its hematopoietic role [41,42]. Unlike other reports from studies that used neuronal cells and neuronal macrophages, Figure 11: Effects of GSK3β inhibitors (lithium and SB216763) as mechanism of inflammation inhibition.…”

supporting

confidence: 91%

The Effect of Lithium on Inflammation-Associated Genes in Lipopolysaccharide-Activated Raw 264.7 Macrophages

Makola

Mbazima

Mokgotho

et al. 2020

International Journal of Inflammation

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Lithium remains the preferred Food and Drug Administration- (FDA-) approved psychiatric drug for treatment of bipolar disorders since its medical establishment more than half a century ago. Recent studies revealed a promising role for lithium in the regulation of inflammation, oxidative stress, and neurodegeneration albeit unclear about its exact mode of action. Thus, the intention of this study is to delineate the regulatory mechanisms of lithium on oxidative stress in lipopolysaccharide- (LPS-) activated macrophages by evaluating its effects on nuclear factor-κB (NF-κB) activity and mRNA expression of multiple oxidative stress-related NF-κB genes. Raw 264.7 macrophages were treated with up to 10 mM lithium, and no change in cell proliferation, viability, growth, and cell adhesion was observed in real time. Pretreatment with low doses of lithium was shown to reduce nitric oxide (NO) production in LPS-activated macrophages. A reduced internal H2DCFDA fluorescence intensity, indicative of reduced reactive oxygen species (ROS) production, was observed in LPS-activated Raw 264.7 macrophages treated with lithium. Lithium has been shown to lower the production of the chemokine RANTES; furthermore, this inhibitory action of lithium has been suggested to be independent of glycogen synthase kinase-3 β (GSK3β) activity. It is shown here that lithium modulates the expression of several inflammatory genes including IκB-α, TRAF3, Tollip, and NF-κB1/p50 which are regulators of the NF-κB pathway. Moreover, lithium inhibits NF-κB activity by lowering nuclear translocation of NF-κB in LPS-activated macrophages. This is the first study to associate Tollip, Traf-3, and IκB-α mRNA expression with lithium effect on NF-κB activity in LPS-activated Raw 264.7 macrophages. Although these effects were obtained using extratherapeutic concentrations of lithium, results of this study provide useful information towards understanding the mode of action of lithium. This study associates lithium with reduced oxidative stress in LPS-activated Raw 264.7 macrophages and further suggests candidate molecular targets for the regulation of oxidative stress-related diseases using lithium beyond bipolar disorders.

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confidence: 91%

The Effect of Lithium on Inflammation-Associated Genes in Lipopolysaccharide-Activated Raw 264.7 Macrophages

Makola

Mbazima

Mokgotho

et al. 2020

International Journal of Inflammation

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“…Overt toxicity develops when the spleen is unable to provide progenitors in response to continued zidovudine exposure in vivo [69]. In zidovudine-treated mice, lithium carbonate [70] and lithium chloride [71] reversed zidovudine toxicity, as measured by increases in peripheral WBC, platelets, and CFU-GM and CFU-Meg hematopoietic progenitors. This effect was optimal at a concentration of 1 mM (PϽ0.05); however, lithium was insufficient in reversing the reduction of erythropoiesis associated with zidovudine use in vivo [72,73].…”

Section: Infectious Neutropeniamentioning

confidence: 99%

Lithium and hematology: established and proposed uses

Focosi

Azzarà

Kast

et al. 2008

Journal of Leukocyte Biology

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Lithium (as lithium carbonate) is an inexpensive drug, widely used in psychiatry for over 50 years in treatment of mood instability (bipolar disorder) and as an adjunct to antidepressants. Hematological effects of neutrophilia and increased circulating CD34+ cells of marrow origin have long been known. Lithium was at the center of hematological investigations in the 1980s, but no definitive use in hematology has yet emerged. We review evidence that lithium increases G-CSF and augments G-CSF effects. We suggest possible therapeutic uses of lithium in neutropenia. In bone marrow transplantation, preharvest lithium-assisted hematopoietic stem cell mobilization may be useful as well.

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“…Lithium has been shown to be an effective agent capable of modulating several aspects of hematopoiesis and protection against suppression of hematopoietic progenitor cells following exposure to radiation at doses commonly used in the treatment of malignant disease [13,14]. It remains unclear how LiCl, by improving the blood circulation and reducing the radiation-induced immunodeficiency [15], protects the germinal cells as evidenced from the present results.…”

Section: Resultsmentioning

confidence: 50%

Effects of lithium chloride as a potential radioprotective agent on radiation response of DNA synthesis in mouse germinal cells

Bhattacharjee

Rajan

Krishnamoorthy

et al. 1997

Radiation and Environmental Biophysics

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Mouse spermatogonial germ cells are highly sensitive to ionizing radiation. Lithium salts are reported to stimulate the postirradiation recovery of hematopoietic marrow cells. We have, therefore, examined whether administered lithium chloride (LiCl) would also be able to protect the mouse germinal cells against radiation injury. Taking DNA synthesis as an endpoint, our results show that the testicular DNA-specific activity in irradiated mice was higher by 61% on average when they had been pretreated with LiCl both 24 h and 1 h prior to gamma-irradiation (2.0 Gy). It was also observed that the DNA synthetic activity in the germinal cells fully recovered after LiCl pretreatment at doses of 40 mg per kg body weight prior to total body irradiation of 0.05-0.25 Gy, whereas at doses of 0.5-6.0 Gy, following the same procedure of LiCl pretreatment, only an incomplete recovery was observed. The dose reduction factor for LiCl is 1.84. The current findings indicate that pretreatment with LiCl provides considerable protection against radiation damage in mouse spermatogonia.

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Modulation of the haematopoietic toxicity associated with zidovudine in vivo with lithium carbonate

Cited by 17 publications

References 18 publications

The Effect of Lithium on Inflammation-Associated Genes in Lipopolysaccharide-Activated Raw 264.7 Macrophages

The Effect of Lithium on Inflammation-Associated Genes in Lipopolysaccharide-Activated Raw 264.7 Macrophages

Lithium and hematology: established and proposed uses

Effects of lithium chloride as a potential radioprotective agent on radiation response of DNA synthesis in mouse germinal cells

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