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

Abstract

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.

Effect of endosulfan and malathion on lipid peroxidation, nitrite and TNF-α release by rat peritoneal macrophages

“…Modulation of the levels of TNF-a is reported for a number of xenobiotics like alcohol, CCl 4 , cadmium chloride, asbestos, titanium dioxide, silica and cotton dust [17].…”

“…Macrophages along with neutrophils are predominant phagocytes and release many cytotoxic and proinflammatory substances to protect the body from wide array of pathogens and xenobiotics [17]. The capacity of these cells to carry out its functions are associated with their state of activation, which in turn is a function of both endogenous (e.g.…”

Time Dependent Gene Expression Changes in the Liver of Mice Treated with Benzene

“…Despite intensive studies over several decades, mechanisms underlying benzene induced toxicity and leukemogenicity are not yet fully understood. They are complicated by various pathways including those of metabolism (Snyder and Hedli, 1996), growth factor regulation (Niculescu, 1995), oxidative stress (Laskin et al 1996), DNA damage (Lee and Garner, 1991), cell cycle regulation (Yoon et al 2001b) and programmed cell death (Ross et al 1996). To elucidate molecular mechanisms of its toxicity, cDNA microarray analyses have been performed by several workers.…”

The Inflammatory and Cytotoxic Effects of a Nitric Oxide Releasing Cream on Normal Skin

“…It is synthesized from arginine by isoforms of NO synthase (NOS) enzymes. The inducible isoform of NO synthase (iNOS) is induced by lipopolysaccharide products of bacterial cell walls or by cytokines, notably tumor necrosis factor α, interferon-γ (Moncada, 1992), interleukin (IL)-1β (Moncada, 1992), IL-6 (Sawada et al, 1997), IL-8 (BruchGerharz et al, 1996), and granulocyte-macrophage colony-stimulating factor (Laskin et al, 1996). Unlike the pmol quantities of NO produced by constitutive endothelial and neuroneal NOS, iNOS produces nanomolar concentrations (Anggard, 1994) which are involved in the immune response to pathogens (Moncada, 1992), in tumor cell necrosis and in apoptosis (Messmer et al, 1994).…”