Toxicology and applied pharmacology
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Toxicol. Appl. Pharmacol. · Oct 1995
Effect of oxygen and sodium thiosulfate during combined carbon monoxide and cyanide poisoning.
In a canine model of combined carbon monoxide (CO) and cyanide (CN) poisoning, cardiac output (QT) and oxygen consumption (Vo2) decreased but recovered to baseline values by 15 min after toxic exposure; elevated blood CN and lactic acidosis persisted for at least another 10 min. Given the rapid spontaneous recovery after cessation of toxic exposure, we questioned the efficacy of usual treatment with oxygen (O2) and sodium thiosulfate (Na2S2O3) for CN poisoning. Accordingly, in seven dogs (26 +/- 3 kg, chloralose and urethane anesthesia), we sequentially administered CO by closed circuit inhalation (231 +/- 42 ml) and potassium CN by intravenous infusion (0.072 mg.kg-1.min-1 for 17 +/- 3 min). ⋯ We conclude that O2 and Na2S2O3 therapy should be continued during combined CO and HCN poisoning. Oxygen increases CO elimination and can enhance anti-CN treatment. After infusion or inhalation of CN, when most CN has already penetrated the intracellular compartment, postexposure sodium thiosulfate increased the metabolism of CN.
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Toxicol. Appl. Pharmacol. · Jan 1995
Comparative StudySuppression of ischemia-reperfusion injury in murine models by neopterins.
We investigated the effects of D-neopterin (NP) and its reduced form, 5,6,7,8-tetrahydro-D-neopterin (NPH4), in two models of ischemia-reperfusion injury, i.e., ischemic paw edema in mice and gastric ischemia in rats. In ischemic paw edema, iv administration of either NP or NPH4 more potently inhibited the increase of paw thickness after release from ischemia than did administration of superoxide dismutase plus catalase or allopurinol. ⋯ The minimum dose of NPH4 required to suppress the gastric ischemic injury in this experiment was 0.3 mg/kg of body weight. These results suggest that neopterin may be effective as a protective agent against ischemia-reperfusion injury, in which active oxygen species are believed to play a major role.
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Toxicol. Appl. Pharmacol. · Aug 1994
Acute inflammatory response to sheep red blood cells in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin: the role of proinflammatory cytokines, IL-1 and TNF.
Recent studies have demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure of C57Bl/6 mice results in an enhanced inflammatory response to intraperitoneal injection of sheep red blood cells (SRBC). This response is characterized by an increase in total peritoneal cells (PEC) as well as an increase in relative and absolute numbers of neutrophils (PMN) harvested 16 to 40 hr following injection of SRBC. The mechanisms whereby TCDD increases cellular influx are unknown. ⋯ Following rhTNFR:Fc treatment, there was no difference between TCDD-treated and control mice in inflammatory cell influx. These results demonstrate that TNF plays a major role in mediating TCDD-induced hyperinflammation. In support of this conclusion, a dose-dependent increase in plasma TNF alpha was measured by ELISA in TCDD-treated mice following SRBC injection.
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Toxicol. Appl. Pharmacol. · Sep 1992
Synergistic interaction of nitrogen dioxide and ozone on rat lungs: acute responses.
Rats were exposed for 6 hr per day to either ozone alone (0.2-0.8 ppm), nitrogen dioxide (NO2) alone (3.6-14.4 ppm), or to combinations of these two oxidant air pollutants. Their response was quantified by changes in the total protein content of lung lavage supernatants or by changes in the content of specific cell types in the lung lavage pellets. A concentration-dependent synergistic response was observed when rats were exposed to the combination of ozone and NO2. ⋯ Agreement between predicted concentrations of ozone and NO2 and those actually observed was excellent. Based upon such modelling estimates and our acute toxicological data, we conclude that synergistic toxicologic interactions between ozone and NO2 are found only at concentrations very much higher than would be encountered in environmental or occupational settings. It remains to be determined whether there are any chronic toxicological responses to exposure to combinations of ozone and NO2 at concentrations below the thresholds for observing acute responses.
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Toxicol. Appl. Pharmacol. · May 1990
Comparative StudyRat embryonic palatal shelves respond to TCDD in organ culture.
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a highly toxic environmental contaminant, is teratogenic in mice, inducing cleft palate (CP) and hydronephrosis at doses which are not overtly maternally or embryo toxic. Palatal shelves of embryonic mice respond to TCDD, both in vivo and in organ culture, with altered differentiation of medial epithelial cells. By contrast, in the rat TCDD produces substantial maternal, embryonic, and fetal toxicity, including fetal lethality, with few malformations. ⋯ The altered differentiation of rat medial epithelium is similar to that reported for TCDD-exposed mouse medial cells in vivo and in vitro. However, in order to obtain these responses, the cultured rat shelves require much higher concentrations of TCDD than the mouse shelves. Thus TCDD induces the same effects at a cellular level in medial epithelium of rats and mice, but cleft palate is not seen in rats because the level required to produce the cellular effects would result in maternal and embryonic toxicity including fetal lethality.