Depression of iron uptake into erythrocytes in mice by treatment with the combined benzene metabolites <i>p</i>‐benzoquinone, muconaldehyde and hydroquinone

Guy, R. L.; Hu, Peidi; Witz, Gisela; Goldstein, Bernard D.; Snyder, Robert

doi:10.1002/jat.2550110611

Cited by 31 publications

(11 citation statements)

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“…Moreover, nitric oxide production by bone marrow cells is inversely correlated with cellular proliferation. Cells from benzenetreated mice exhibited increased sensitivity to nitric oxide-mediated growth inhibition, a finding consistent with the idea that nitric oxide contributes to the reduced bone marrow cellularity and impaired hematopoiesis observed after benzene exposure (7,22,23 25 mg/kg 1 ,2,4-benzenetriol, 2 mg/kg p-benzoquinone, or corn oil control once/day for 3 days or twice/day for 2 days. These treatment protocols were found to induce bone marrow suppression (24)(25)(26).…”

Section: Introductionsupporting

confidence: 68%

Role of nitric oxide in hematosuppression and benzene-induced toxicity.

Laskin

Heck

Punjabi

et al. 1996

Environ Health Perspect

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It is becoming increasingly apparent that nitric oxide plays a multifunctional role in regulating inflammatory processes in the body. Although nitric oxide and its oxidation products are cytotoxic toward certain pathogens, they can also cause tissue injury and suppress proliferation. Cytokines and growth factors released at sites of inflammation or injury stimulate both immune and nonimmune cells to produce nitric oxide. Nowhere in the body is this more detrimental than in the bone marrow, for the continuous production of hematopoietic precursors is essential for normal blood cell maturation. Our laboratories have discovered that, in response to inflammatory mediators, bone marrow cells readily produce nitric oxide. Nitric oxide production is enhanced by hematopoietic growth factors including interleukin-3, macrophage colony stimulating factor, and granulocyte-macrophage colony-stimulating factor. When bone marrow cells produce nitric oxide, hematopoiesis is impaired, an effect that is potentiated by colony-stimulating factors. Treatment of mice with benzene, which suppresses bone marrow cell development, was found to markedly enhance the ability of bone marrow cells to produce nitric oxide in response to inflammatory mediators alone and in combination with hematopoietic growth factors. Taken together, these data suggest that nitric oxide may be an important mediator of benzene-induced bone marrow suppression.

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Section: Introductionsupporting

confidence: 68%

Role of nitric oxide in hematosuppression and benzene-induced toxicity.

Laskin

Heck

Punjabi

et al. 1996

Environ Health Perspect

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“…Since that report, other studies have generally corroborated these findings. Coadministration with phenol has been found to decrease the metabolic clearance of HQ 65 and to exacerbate the inhibition of erythrocyte iron uptake, 271,272 formation of macromolecular adducts, 64,106,111,409 generation of activated oxygen species, 410 and MN induction 162 encountered with HQ exposure alone. Stimulation of HQ metabolism by myeloperoxidase has also been demonstrated for BQ 411 and additional phenolic compounds.…”

Section: Conclusion: Implications For Human Health Effectsmentioning

confidence: 98%

“…injection of 100 mg/kg HQ in mice. [269][270][271][272] The effect of HQ on growth of burst-forming unit, erythroid (BFU-E), colonyforming unit, erythroid (CFU-E), and CFU-C colonies from mouse bone marrow revealed CFU-E activity to be most sensitive, with suppression observed at low micromolar concentrations. 273 Dose-dependent inhibition of CFU-E and BFU-E was observed in HQ-treated SW and C57B1/6J mouse and human bone marrow cells, respectively.…”

Section: Myelotoxicity and Immunotoxicitymentioning

confidence: 99%

The Toxicology of Hydroquinone — Relevance to Occupational and Environmental Exposure

DeCaprio¹

1999

Critical Reviews in Toxicology

175

128

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Hydroquinone (HQ) is a high-volume commodity chemical used as a reducing agent, antioxidant, polymerization inhibitor, and chemical intermediate. It is also used in over-the-counter (OTC) drugs as an ingredient in skin lighteners and is a natural ingredient in many plant-derived products, including vegetables, fruits, grains, coffee, tea, beer, and wine. While there are few reports of adverse health effects associated with the production and use of HQ, a great deal of research has been conducted with HQ because it is a metabolite of benzene. Physicochemical differences between HQ and benzene play a significant role in altering the pharmacokinetics of directly administered when compared with benzene-derived HQ. HQ is only weakly positive in in vivo chromosomal assays when expected human exposure routes are used. Chromosomal effects are increased significantly when parenteral or in vitro assays are used. In cancer bioassays, HQ has reproducibly produced renal adenomas in male F344 rats. The mechanism of tumorigenesis is unclear but probably involves a species-, strain-, and sex-specific interaction between renal tubule toxicity and an interaction with the chronic progressive nephropathy that is characteristic of aged male rats. Mouse liver tumors (adenomas) and mononuclear cell leukemia (female F344 rat) have also been reported following HQ exposure, but their significance is uncertain. Various tumor initiation/promotion assays with HQ have shown generally negative results. Epidemiological studies with HQ have demonstrated lower death rates and reduced cancer rates in production workers when compared with both general and employed referent populations. Parenteral administration of HQ is associated with changes in several hematopoietic and immunologic endpoints. This toxicity is more severe when combined with parenteral administration of phenol. It is likely that oxidation of HQ within the bone marrow compartment to the semiquinone or p-benzoquinone (BQ), followed by covalent macromolecular binding, is critical to these effects. Bone marrow and hematologic effects are generally not characteristic of HQ exposures in animal studies employing routes of exposure other than parenteral. Myelotoxicity is also not associated with human exposure to HQ. These differences are likely due to significant route-dependent toxicokinetic factors. Fetotoxicity (growth retardation) accompanies repeated administration of HQ at maternally toxic dose levels in animal studies. HQ exposure has not been associated with other reproductive and developmental effects using current USEPA test guidelines. The skin pigment lightening properties of HQ appear to be due to inhibition of melanocyte tyrosinase. Adverse effects associated with OTC use of HQ in FDA-regulated products have been limited to a small number of cases of exogenous ochronosis, although higher incidences of this syndrome have been reported with inappropriate use of unregulated OTC products containing higher HQ concentrations. The most serious human health effect related to HQ is p...

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“…Ringopened metabolites may also form; the most common of these found in the urine are trans-trans-muconic acid (t, t-MA) and 6-hydroxy-t, t-2,4-hexadienoic acid (Seaton et al, 1994;Snyder and Hedli, 1996). While each of these metabolites can exert its own toxicity in situ, various combinations of the metabolites can exert a synergistic effect on multiple cellular targets, leading to increased toxicity (Guy et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Green Tea Attenuates Benzene-Induced Oxidative Stress in Pump Workers

Emara

El-Bahrawy

2008

Journal of Immunotoxicology

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Workers exposed to benzene frequently suffer from toxicities of the bone marrow as well as the central nervous, immune, and reproductive systems. This toxicity most likely is a result of the oxidative metabolism of benzene to reactive products. As green tea possesses antioxidant effects, the objective of this study was to examine any amelioration of benzene-induced oxidative stress in pump workers drinking 6 cups (150 ml/cup) of freshly prepared tea daily. Sixty male non-smoking subjects, divided into four groups: no benzene exposure/no green tea; no exposure/tea; exposure/no tea; and, exposure/tea, were monitored after a 6 mo period. On the final day of the study, urine samples were collected for analyses of benzene, trans-trans muconic acid, and phenol. Blood was also collected at this time; plasma was assayed for total antioxidant activity, malondialdehyde (MDA), and glutathione (GSH) while erythrocytes were analyzed for activity of antioxidant enzymes glutathione peroxidase (GSHPX), superoxide dismutase (SOD), and catalase. The results demonstrated that urinary levels of benzene, trans-trans muconic acid, and phenol were elevated in all pump workers, and that this elevation was mitigated by consumption of green tea. The benzene exposures also led to significant reductions in plasma GSH levels and erythrocyte antioxidant enzyme activities; these effects were abrogated (to near-control levels) by the tea. Interestingly, among control subjects, tea ingestion itself caused significant increases in both GSHPX and catalase activities. Unlike with the other plasma parameters, while the benzene exposures also significantly increased plasma MDA levels and decreased total antioxidant activity, tea ingestion did not cause a near-total reversion to control values; the effects on these two endpoints were more like those noted with the urine parameters (mitigation, not abrogation). These studies demonstrate that drinking green tea during benzene exposure can reduce several parameters indicative of oxidative stress. As such, as a dietary supplement, green tea could represent a potential therapeutic agent in reducing certain aspects of benzene-induced toxicity.

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Depression of iron uptake into erythrocytes in mice by treatment with the combined benzene metabolites p‐benzoquinone, muconaldehyde and hydroquinone

Cited by 31 publications

References 9 publications

Role of nitric oxide in hematosuppression and benzene-induced toxicity.

Role of nitric oxide in hematosuppression and benzene-induced toxicity.

The Toxicology of Hydroquinone — Relevance to Occupational and Environmental Exposure

Green Tea Attenuates Benzene-Induced Oxidative Stress in Pump Workers

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