Cigarette smoking remains a significant health threat for smokers and nonsmokers alike. Secondhand smoke (SHS) is intrinsically more toxic than directly inhaled smoke. Recently, a new threat has been discovered – Thirdhand smoke (THS) – the accumulation of SHS on surfaces that ages with time, becoming progressively more toxic. THS is a potential health threat to children, spouses of smokers and workers in environments where smoking is or has been allowed. The goal of this study is to investigate the effects of THS on liver, lung, skin healing, and behavior, using an animal model exposed to THS under conditions that mimic exposure of humans. THS-exposed mice show alterations in multiple organ systems and excrete levels of NNAL (a tobacco-specific carcinogen biomarker) similar to those found in children exposed to SHS (and consequently to THS). In liver, THS leads to increased lipid levels and non-alcoholic fatty liver disease, a precursor to cirrhosis and cancer and a potential contributor to cardiovascular disease. In lung, THS stimulates excess collagen production and high levels of inflammatory cytokines, suggesting propensity for fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma. In wounded skin, healing in THS-exposed mice has many characteristics of the poor healing of surgical incisions observed in human smokers. Lastly, behavioral tests show that THS-exposed mice become hyperactive. The latter data, combined with emerging associated behavioral problems in children exposed to SHS/THS, suggest that, with prolonged exposure, they may be at significant risk for developing more severe neurological disorders. These results provide a basis for studies on the toxic effects of THS in humans and inform potential regulatory policies to prevent involuntary exposure to THS.
Magnetic resonance imaging (MRI) is increasingly used in the assessment of the severity and progression of neurotrauma. We evaluated temporal and regional changes after mild fluid percussion (FPI) and controlled cortical impact (CCI) injury using T2-weighted-imaging (T2WI) and diffusion-weighted imaging (DWI) MRI over 7 days. Region of interest analysis of brain areas distant to the injury site (such as the hippocampus, retrosplenial and piriform cortices, and the thalamus) was undertaken. In the hippocampus of CCI animals, we found a slow increase (51%) in apparent diffusion coefficients (ADC) over 72 h, which returned to control values. The hippocampal T2 values in the CCI animals were elevated by 18% over the 7-day time course compared to control, indicative of edema formation. Histological analysis supported the lack of overt cellular loss in most brain regions after mild CCI injury. FPI animals showed a generalized decrease in hippocampal ADC values over the first 72 h, which then returned to sham levels, with decreased T2 values over the same period, which remained depressed at 7 days. Histological assessment of FPI animals revealed numerous shrunken cells in the hippocampus and thalamus, but other regions showed little damage. Increased immunohistochemical staining for microglia and astroglia at 7 days post-injury was greater in FPI animals within the affected brain regions. In summary, traumatic brain injury is less severe in mild CCI than FPI, based on the temporal events assessed with MRI.
Polybrominated diphenyl ethers (PBDEs) are brominated flame retardant chemicals and environmental contaminants with endocrine-disrupting properties that are associated with diabetes and metabolic syndrome in humans. However, their diabetogenic actions are not completely characterized or understood. In this study, we investigated the effects of DE-71, a commercial penta-mixture of PBDEs, on glucoregulatory parameters in a perinatal exposure model using female C57Bl/6 mice. Results from in vivo glucose and insulin tolerance tests and ex vivo analyses revealed fasting hyperglycemia, glucose intolerance, reduced sensitivity and delayed glucose clearance after insulin challenge, decreased thermogenic brown adipose tissue mass, and exaggerated hepatic endocannabinoid tone in F1 offspring exposed to 0.1 mg/kg DE-71 relative to control. DE-71 effects on F0 dams were more limited indicating that indirect exposure to developing offspring is more detrimental. Other ex vivo glycemic correlates occurred more generally in exposed F0 and F1, i.e., reduced plasma insulin and altered glucoregulatory endocrines, exaggerated sympathoadrenal activity and reduced hepatic glutamate dehydrogenase enzymatic activity. Hepatic PBDE congener analysis indicated maternal transfer of BDE-28 and -153 to F1 at a collective level of 200 ng/g lipid, in range with maximum values detected in serum of human females. Given the persistent diabetogenic phenotype, especially pronounced in female offspring after developmental exposure to environmentally relevant levels of DE-71, additional animal studies should be conducted that further characterize PBDE-induced diabetic pathophysiology and identify critical developmental time windows of susceptibility. Longitudinal human studies should also be conducted to determine the risk of long-lasting metabolic consequences after maternal transfer of PBDEs during early-life development.
Polybrominated diphenyl ethers (PBDEs) are widely used as additive flame-retardants and have been detected in human blood, adipose tissue, and breast milk. Developmental and long-term exposures to these chemicals may pose a human health risk, especially to children. We have previously demonstrated that polychlorinated biphenyls (PCBs), which are structurally similar to PBDEs and cause neurotoxicity, perturb intracellular signaling events including calcium homeostasis and protein kinase C translocation, which are critical for neuronal function and development of the nervous system. The objective of the present study was to test whether environmentally relevant PBDE congeners 47 and 99 are also capable of disrupting Ca(2+) homeostasis. Calcium buffering was determined by measuring (45)Ca(2+)-uptake by microsomes and mitochondria, isolated from adult male rat brain (frontal cortex, cerebellum, hippocampus, and hypothalamus). Results show that PBDEs 47 and 99 inhibit both microsomal and mitochondrial (45)Ca(2+)-uptake in a concentration-dependent manner. The effect of these congeners on (45)Ca(2+)-uptake is similar in all four brain regions though the hypothalamus seems to be slightly more sensitive. Among the two preparations, the congeners inhibited (45)Ca(2+)-uptake in mitochondria to a greater extent than in microsomes. These results indicate that PBDE 47 and PBDE 99 congeners perturb calcium signaling in rat brain in a manner similar to PCB congeners, suggesting a common mode of action of these persistent organic pollutants.
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