Toxicology letters
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Harmful and potential harmful chemicals (HPHCs) and oxidative stress of macrophages are major factors responsible for smoking-caused chronic respiratory diseases. However, comparisons of HPHCs among heat not burn (HnB) product and ultra-light cigarette and their induced oxidative stress of macrophages have not been investigated. ⋯ Conclusively, most HPHCs from HnB were lower than that from ultra-light, while certain harmful chemicals were higher than ultra-light, e.g., carbonyl compounds. HnB-induced oxidative stress of macrophages is less than ultra-light cigarette.
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Carfentanil is an ultra-potent opioid with an analgesic potency 10,000 times that of morphine but has received little scientific investigation. Three experiments were conducted to evaluate the toxicity of carfentanil and the efficacy of naloxone in adult male African green monkeys. The first experiment determined the ED50 (found to be 0.71 μg/kg) of subcutaneous carfentanil for inducing bradypnea and/or loss of posture. ⋯ Experiment 3 evaluated the effects of carfentanil (0.575 μg/kg) alone, the safety of naloxone (71-2841 μg/kg), and the efficacy of naloxone (71-710 μg/kg) administration at two time points following carfentanil (1.15 μg/kg) on operant choice reaction time. Collectively, these experiments characterized the temporal progression of carfentanil-induced toxic signs, determined the range of naloxone doses that restored respiratory and gross behavioral function, and determined the time course and range of naloxone doses that partially or completely reversed the effects of carfentanil on operant choice reaction time performance in African green monkeys. These results have practical relevance for the selection of opioid antagonists, initial doses, and expected functional outcomes following treatment of synthetic opioid overdose in a variety of operational/emergency response contexts.
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"Heat-not-burn" tobacco products are designed to heat processed tobacco instead of combusting it, thus significantly reducing the formation of harmful and potentially harmful constituents (HPHCs) found in cigarette smoke, and ultimately reducing the risk of smoking-related diseases. The Carbon-Heated Tobacco Product (CHTP), a heat-not-burn tobacco product similar in appearance and use ritual to cigarettes, has been developed for smokers who would otherwise continue smoking as an alternative to cigarettes. To evaluate reduced risk of harm potential of CHTP, it is critical to quantify exposure to HPHCs and consequent biological pathway disturbances involved in disease onset in smokers who switch to CHTP. ⋯ Switching from cigarettes to CHTP resulted in significantly reduced exposure to HPHCs and was associated with observed improvements in some biomarkers of effect representative of pathomechanistic pathways underlying the development of smoking-related diseases.
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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no effective medication. Andrographolide (Andro), extracted from Chinese herbal Andrographis paniculata, could attenuate bleomycin (BLM)-induced pulmonary fibrosis via inhibition of inflammation and oxidative stress, however, the anti-fibrotic mechanisms have not been clarified. Myofibroblasts are the primary cell types responsible for the accumulation of extracellular matrix (ECM) in fibrotic diseases, and targeting fibroblast proliferation and differentiation is an important therapeutic strategy for the treatment of IPF. ⋯ Andro also inhibited TGF-β1-induced myofibroblast differentiation and ECM deposition in both cells. We also found that Andro suppressed TGF-β1-induced Smad2/3 and Erk1/2 activation, suggesting that Smad2/3 and Erk1/2 inactivation mediates Andro-induced effects on TGF-β1-induced fibroblast proliferation and differentiation. These results indicated that Andro has novel and potent anti-fibrotic effects in lung fibroblasts via inhibition of the proliferation and myofibroblast differentiation of fibroblasts and subsequent ECM deposition, which are modulated by TGF-β1-mediated Smad-dependent and -independent pathways.
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Silver ion has strong antimicrobial properties and is used in a number of wound dressings. In burn models, silver-nylon dressings produce elevated silver levels in the wound along with minimal systemic effect. We evaluated systemic toxicity in a non-burn wound model to see if a similar pattern of silver ion distribution would occur. ⋯ A 21-day application of silver-nylon dressings to a non-burn dermal wound produces no systemic or local toxicity in Gottingen minipigs.