Abderrahim Nemmar

BACKGROUND/AIMS: The components of cigarette smoke (CS) have been implicated in the development of cancer as well as in cardiopulmonary diseases. We have previously reported increased oxidative stress in rat tissues induced by tobacco-specific toxins nicotine and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Recently, we have also shown increased oxidative stress and associated inflammatory responses in various tissues after exposure to cigarette smoke. METHODS: In this study, we have further investigated the effects of nose-only cigarette smoke exposure on mitochondrial functions and glutathione-dependent redox metabolism in tissues of BALB/C mice. Liver, kidney, heart and lung tissues were analyzed for oxidative stress, glutathione (GSH) and cytochrome P450 dependent enzyme activities and mitochondrial functions after exposure to smoke generated by 9 cigarettes/day for 4 days. Control mice were exposed to air only. RESULTS: An increase in oxidative stress as observed by increased production of reactive oxygen species (ROS) and altered GSH metabolism was apparent in all the tissues, but lung and heart appeared to be the main targets. Increased expression and activity of CYP450 1A1 and 1A2 were also observed in the tissues after exposure to cigarette smoke. Mitochondrial respiratory dysfunction in the tissues, as observed by alterations in the activities of Complex I and IV enzymes, was also observed after exposure to cigarette smoke. SDS-PAGE and Western blot results also indicate that alterations in the expression of enzyme proteins were in accordance with the changes in their catalytic functions. CONCLUSION: These results suggest that even short term exposure of cigarette smoke have adverse effects on mitochondrial functions and redox homeostasis in tissues which may progress to further complications associated with chronic smoking.

BACKGROUND: Pollution by particulates has been consistently associated with increased cardiovascular morbidity and mortality. However, the mechanisms responsible for these effects are not well-elucidated. METHODS AND RESULTS: To assess to what extent and how rapidly inhaled pollutant particles pass into the systemic circulation, we measured, in 5 healthy volunteers, the distribution of radioactivity after the inhalation of "Technegas," an aerosol consisting mainly of ultrafine (99m)Technetium-labeled carbon particles (<100 nm). Radioactivity was detected in blood already at 1 minute, reached a maximum between 10 and 20 minutes, and remained at this level up to 60 minutes. Thin layer chromatography of blood showed that in addition to a species corresponding to oxidized (99m)Tc, ie, pertechnetate, there was also a species corresponding to particle-bound (99m)Tc. Gamma camera images showed substantial radioactivity over the liver and other areas of the body. CONCLUSIONS: We conclude that inhaled (99m)Tc-labeled ultrafine carbon particles pass rapidly into the systemic circulation, and this process could account for the well-established, but poorly understood, extrapulmonary effects of air pollution.

Engineered nanomaterials (ENMs) have gained huge importance in technological advancements over the past few years. Among the various ENMs, silver nanoparticles (AgNPs) have become one of the most explored nanotechnology-derived nanostructures and have been intensively investigated for their unique physicochemical properties. The widespread commercial and biomedical application of nanosilver include its use as a catalyst and an optical receptor in cosmetics, electronics and textile engineering, as a bactericidal agent, and in wound dressings, surgical instruments, and disinfectants. This, in turn, has increased the potential for interactions of AgNPs with terrestrial and aquatic environments, as well as potential exposure and toxicity to human health. In the present review, after giving an overview of ENMs, we discuss the current advances on the physiochemical properties of AgNPs with specific emphasis on biodistribution and both in vitro and in vivo toxicity following various routes of exposure. Most in vitro studies have demonstrated the size-, dose- and coating-dependent cellular uptake of AgNPs. Following NPs exposure, in vivo biodistribution studies have reported Ag accumulation and toxicity to local as well as distant organs. Though there has been an increase in the number of studies in this area, more investigations are required to understand the mechanisms of toxicity following various modes of exposure to AgNPs.

The mechanisms of particulate pollution-related cardiovascular morbidity and mortality are not well understood. We studied the passage of radioactively labeled ultrafine particles after their intratracheal instillation. Hamsters received a single intratracheal instillation of 100 microg albumin nanocolloid particles (nominal diameter < or = 80 nm) labeled with 100 microCi technetium-99m and were killed after 5, 15, 30, and 60 min. In blood, radioactivity, expressed as percentage of total body radioactivity per gram blood, amounted to 2.88 +/- 0.80%, 1.30 +/- 0.17%, 1.52 +/- 0.46%, and 0.21 +/- 0.06% at 5, 15, 30, and 60 min, respectively. Thin-layer chromatography showed only one peak of radioactivity corresponding to unaltered (99m)Tc-albumin nanocolloid. In the liver, radioactivity, expressed as percentage of total radioactivity per organ, amounted to 0.10 +/- 0.07%, 0.23 +/- 0.06%, 1.24 +/- 0.27%, and 0.06 +/- 0.02% at 5, 15, 30, and 60 min, respectively. Lower values were observed in the heart, spleen, kidneys, and brain. Dose dependence was assessed at 30 min following instillation of 10 microg and 1 microg (99m)Tc-albumin per animal (n = 3 at each dose), and values of the same relative magnitudes as after instillation of 100 microg were obtained. We conclude that a significant fraction of (99m)Tc-albumin, taken as a model of ultrafine particles, rapidly diffuses from the lungs into the systemic circulation.