Macrophage Secretory Function Is Enhanced by Low Doses of Tributyltin-Oxide (TBTO), But Not Tributyltin-Chloride (TBTCl)

Abstract

Numerous studies suggest that tributyltin (TBT) is a potent immunotoxicant in nontarget organisms with lymphoid atrophy being a hallmark response. Two of the most common formulations of TBT are bis (tri-n-butyl)-tin oxide (TBTO) and tri-n-butyl-tin chloride (TBTCl). Most of studies investigating TBT-related immunotoxicity have used relatively high doses of both compounds, but little is known about the effects of very low doses. In addition, no studies have directly compared the effects of both formulations on immune function(s). We exposed female B6C3F1 mice to a single dose of TBTO or TBTCl at 0.3, 3.0, 30 mM/kg or corn oil as a carrier control. Forty-eight h later mice received a 4% solution of thioglycolate intraperitoneally to elicit peritoneal macrophages. Ninety-six h later macrophages were harvested and stimulated with a mixture of gamma-interferon (IFN-gamma) and lipopolysaccharide (LPS). Nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor beta-1 (TGF-beta1), and phorbol ester-stimulated oxidative burst activity were then measured. Nitric oxide and TNF-alpha production were significantly elevated in the 0.3 and 3.0 mM TBTO/kg-treated groups but not in those treated by TBTCl. Background TNF-alpha production (without stimulation) was also elevated at these two doses but suppressed in TBTCl-treated animals. Oxidative burst activity was elevated at 0.3 mM TBTO/kg but not by TBTCl. TGF-beta1 production was not altered by either treatment, nor were body wts and organ-body wt ratios. To further evaluate the difference between the effects of TBTO and TBTCl on macrophage function, the in vitro toxicity of the two was determined using elicited peritoneal macrophages from untreated mice. Following a 24-h exposure to increasing concentrations of TBTO or TBTCl, functional viability was evaluated using the MTT assay. There were no differences between the two compounds in terms of treatment-related viability except that at the very highest concentrations (10(-6) M) TBTO was more toxic than TBTCl.

NADPH-diaphorase activity in the central nervous system of the Gray mussel Crenomytilus grayanus (Dunker) under stress conditions: A histochemical study

“…Kergosien and Rice (1998) showed that tributyltinoxide (TBTO) (in a dose up to 3.0 lM/kg of body weight), but not tributyltinchloride (TBTCl), induced a reversible increase in NO production in mouse macrophages. Smith and coauthors (2000) showed that relatively low TBTO concentrations (0.001-0.01 mg/l) induced an increase in NO production in hemocytes of the mussel Mytilus edulis, while high concentrations of the toxicant (0.1 mg/l) significantly inhibited NO production.…”

Cytotoxicity of tributyltin in rat hippocampal slice cultures

“…Additionally, we cannot rule out the possible involvement of other types of radicals. Indeed Kergosien and Rice (1998) reported that TBT enhances nitric oxide production in macrophages. Therefore, various radicals including nitric oxide may be, in part, involved in TBT toxicity.…”

The Effects of Indirubin-3′-Monoxime, A Novel AHR Ligand, on Stress and Toxicity-Related Gene/Protein Expression in Human U937 Cells Undergoing Differentiation and Activation

“…The four treatment regimens are as follows: (A) undifferentiated cells (monocytes) treated with 10 µM tributyltin-chloride (TBT), a well characterized and highly leukocytotoxic agent (Kergosien and Rice, 1998), as a positive control for cytotoxicity, 10 µM indirubin-3 -monoxime, 1 µM indirubin-3 -monoxime or DMSO as carrier control for 24 hrs; (B) U937 cells were differentiated for 24 hrs in the presence of 0.1 µM PMA, then treated with 10 µM TBT, 10 µM indirubin-3 -monoxime, 1 µM indirubin-3 -monoxime, or DMSO as carrier control for 24 hrs; (C) undifferentiated U937 cells were treated with 10 µM TBT, 10 µM indirubin-3 -monoxime, 1 µM indirubin-3 -monoxime or DMSO as carrier control for 24 hrs followed by a 24-hr period of differentiation in the presence of PMA (effects of treatment on the differentiation process); and (D) U937 cells were differentiated in the presence of 0.1 µM PMA for 24 hrs, the culture medium removed and replaced with fresh media containing 0.1 µM PMA and 1 µg/ml LPS (Salmonella typhimurium; Sigma) for 24 hrs to yield differentiated and activated cells, followed by a 24-hr exposure to 10 µM TBT, 10 µM indirubin-3 -monoxime, 1 µM indirubin-3 -monoxime or DMSO as carrier control. All treatments, including the DMSO carrier control, were conducted in six replicated wells of a 96-well plate per treatment.…”