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[Display omitted] • In the right breast RT, VMAT technique showed a better dose conformity than 3D-CRT. • MATIL is a good parameter to predict the need of VMAT to limit V20Gy of the IL. • VMAT, according to the ipsilateral lung second cancer risk, seems justified. In the adjuvant right breast radiation therapy, after breast-conserving surgery, we wanted to look for a parameter that would help in the choice between the 3D-CRT or VMAT techniques, considering the risk of pneumonia to the ipsilateral lung (IL) linked to high doses. We also investigated the risk of second tumors in the IL related to the VMAT low doses. We examined twenty-five 3D-CRT and thirty-five VMAT technique plans, between September 2022 and September 2023. We collected the MAximum Thickness of Ipsilateal Lung (MATIL) included between lateral and medial target borders for evaluating the risk of pneumonia due to the high dose (V 20Gy), finally we calculated the Excess of Absolute Risk related to the second tumor risk due to the low dose. VMAT technique showed a better dose conformity than 3D-CRT. We detected a linear relationship between the V 20Gy and MATIL of the IL only for the 3D-CRT technique; over a threshold value of MATIL the 3D-CRT is disadvantaged compared to the VMAT in terms of the risk of toxicity to the IL. We calculated that for every Gy more in average dose, a 12 % increase in the risk of induced cancer is expected. In the adjuvant right breast RT, the MATIL is a good surrogate parameter to predict the need to use a VMAT technique to limit high doses to IL. VMAT technique, according to the IL second tumor estimated risk, seems justified. [ABSTRACT FROM AUTHOR]

Radiation-induced lung injury (RILI) that is usually divided into an early radiation-induced pneumonitis (RIP) and late chronic radiation-induced lung fibrosis (RILF) remains a clinically significant toxicity in radiation oncology. Thus, a thorough understanding of underlying molecular mechanisms and risk factors is crucial. This review, focused on patients treated with modern radiotherapy (RT ) techniques, describes the different clinical presentations of RIP, with most typical imaging findings and usefulness of pulmonary function tests and laboratory assessment in differential diagnosis. The most critical patient- and treatment- related predictors are summarized and discussed — age and sex, comorbidities, tumour characteristics, concomitant treatment, and RT -plan parameters. The conventional grading scales and contemporary approach to quantitative assessment (radiomics, CT density changes) is described as well as treatment methods. [ABSTRACT FROM AUTHOR]

Cigarettes and other tobacco products are used to obtain nicotine that is responsible for their stimulating effects. However, a lot of other organic and inorganic chemicals are also released along with nicotine. Cadmium (Cd) is one of the several heavy metals that are health hazards and is one of the inorganic elements released in tobacco smoke. The in-vitro investigation focused on exploring the effects of nicotine hydrogen tartrate (NHT) and cadmium (Cd) and their toxic interactions in the A549 cell line. In cell viability assay NHT exhibited its IC 50 at 11.71 mM concentration, and the IC 50 of Cd was found to be 83 µM after a 24 h exposure. Toxic effects of NHT (5 mM and 10 mM), Cd (50 µM and 100 µM), and their combination were also investigated by flowcytometry. The investigation included apoptotic and necrotic events, the effect on different cell cycle phases, and generation of reactive oxygen species by NHT, Cd, and their combination of different concentrations. Data reveal evident toxic effects of NHT, Cd, and NHT + Cd. It also indicates that the toxic interaction of NHT and Cd is not additive and appears to be minimal when compared with NHT or Cd exposures alone. [ABSTRACT FROM AUTHOR]

The contribution of diesel exhaust to atmospheric pollution is a major concern for public health, especially in terms of occurrence of lung cancers. The present study aimed at addressing the toxic effects of a repeated exposure to these emissions in an animal study performed under strictly controlled conditions. Rats were repeatedly exposed to the exhaust of diesel engine. Parameters such as the presence of a particle filter or the use of gasoil containing rapeseed methyl ester were investigated. Various biological parameters were monitored in the lungs to assess the toxic and genotoxic effects of the exposure. First, a transcriptomic analysis showed that some pathways related to DNA repair and cell cycle were affected to a limited extent by diesel but even less by biodiesel. In agreement with occurrence of a limited genotoxic stress in the lungs of diesel-exposed animals, small induction of γ-H2AX and acrolein adducts was observed but not of bulky adducts and 8-oxodGuo. Unexpected results were obtained in the study of the effect of the particle filter. Indeed, exhausts collected downstream of the particle filter led to a slightly higher induction of a series of genes than those collected upstream. This result was in agreement with the formation of acrolein adducts and γH2AX. On the contrary, induction of oxidative stress remained very limited since only SOD was found to be induced and only when rats were exposed to biodiesel exhaust collected upstream of the particle filter. Parameters related to telomeres were identical in all groups. In summary, our results point to a limited accumulation of damage in lungs following repeated exposure to diesel exhausts when modern engines and relevant fuels are used. Yet, a few significant effects are still observed, mostly after the particle filter, suggesting a remaining toxicity associated with the gaseous or nano-particular phases. [ABSTRACT FROM AUTHOR]

Pollution from fine particulate matter (PM2.5) has become a major threat to public health and has been related to lung toxicity. One of the key regulators of the Hippo signaling system, Yes-associated protein 1 (YAP1), is speculated to play a role in ferroptosis development. Here, we focused on investigating the function of YAP1 in pyroptosis and ferroptosis, aiming to explore its therapeutic potential in PM2.5-induced lung toxicity. PM2.5-induced lung toxicity was induced in Wild-type WT and conditional YAP1-knockout mice, and lung epithelial cells were stimulatd by PM2.5 in vitro. We used western blot, transmission electron microscopy, and fluorescence microscopy to investigate pyroptosis- and ferroptosis-related characteristics. We found that PM2.5 leads to lung toxicity using mechanisms involving pyroptosis and ferroptosis. YAP1 knockdown impeded pyroptosis, ferroptosis, and PM2.5-induced lung damage, as shown by increased histopathology, higher levels of proinflammatory cytokines, GSDMD protein, lipid peroxidation, and iron accumulation, as well as increased NLRP3 inflammasome activation and decreased SLC7A11 expression. YAP1 silencing consistently promoted NLRP3 inflammasome activation and reduced SLC7A11 levels, aggravating PM2.5-induced cellular damage. In contrast, YAP1-overexpressing cells inhibited NLRP3 inflammasome activation and increased SLC7A11 levels, preventing pyroptosis and ferroptosis. Overall, our data suggest that YAP1 ameliorates PM2.5-induced lung injury by inhibiting NLRP3-mediated pyroptosis and SL7A11-dependent ferroptosis. [Display omitted] • Pyroptosis and ferroptosis are major contributors to PM2.5-induced lung toxicity. • YAP1 deficiency aggravated, but YAP1 overexpression alleviated, PM2.5-induced lung toxicity. • YAP1's protective function in PM2.5-induced toxicity was linked to suppression of pyroptosis and ferroptosis. [ABSTRACT FROM AUTHOR]

During the last few years, the induction of toxicological mechanisms by atmospheric ultrafine particles (UFP) has become one of the most studied topics in toxicology and a subject of huge debates. Fine particles (FP) and UFP collected at urban and rural sites in Lebanon were studied for their chemical composition and toxicological effects. UFP were found more enriched in trace elements, secondary inorganic ions, total carbon and organic compounds than FP. For toxicological analysis, BEAS-2B cells were exposed for 24, 48 and 72 h to increasing concentrations of FP, water-UFP suspension (UFP w ) and UFP organic extract (UFP org ). Our findings showed that UFP caused earlier alterations of mitochondrial metabolism and membrane integrity from the lowest concentrations. Moreover, a significant induction of CYP1A1, CYP1B1 and AhRR genes expression was showed after cells exposure to UFP org and to a lesser extent to UFP w and FP samples. [ABSTRACT FROM AUTHOR]

Summary This paper describes a case of lung injury attributed to the use of Nitrofurantoin and a review of the relevant literature. An 88-year-old woman was admitted to the floor for the evaluation of recent symptoms of dyspnea, fatigue and productive cough. She was initiated on nitrofurantoin 300 mg per day for the treatment of a urinary tract infection 3 days earlier. Upon examination, chest auscultation revealed bilateral inspiratory crackles. Chest radiograph showed bilateral airspace and interstitial infiltrates. Laboratory studies revealed an elevated white blood cell count of 13,500/μL (reference range = 5200–12,400/μL) and blood eosinophilia (10%, reference range: 0–7%). Using clinical judgment and the algorithm of Naranjo, it was determined that nitrofurantoin use was the probable cause of the patient's lung injury. Symptomatic improvement was observed shortly after the drug was discontinued. A review of information from several European and North American pharmacovigilance databases (through June 2014) identified several reports of suspected nitrofurantoin-induced toxicity, including reports of acute toxicity reactions, which were related in many ways to the case we are reporting here. [ABSTRACT FROM AUTHOR]

Giant cell interstitial pneumonia (GIP) is a rare form of chronic interstitial pneumonia typically associated with hard metal exposure. Only two cases of GIP induced by nitrofurantoin have been reported in the medical literature. We are reporting a case of recurrent nitrofurantoin-induced GIP. Although extremely rare, GIP needs to be included in the differential diagnosis in patients with chronic nitrofurantoin use who present with respiratory illness. [ABSTRACT FROM AUTHOR]

To study the regulatory relationship between ozone-induced mitophagy and pyroptosis in lung epithelial cells. First, type I primary alveolar epithelial cells and male Wistar rats were treated with ozone at different dosages. The ATP content and mitochondrial membrane potential significantly decreased in type I primary alveolar epithelial cells. The mitophagy-related markers and PINK1/Parkin pathway-related proteins, and the co-localization of LC3, Parkin, and mitochondria in type I alveolar epithelial cells indicated that ozone exposure triggered mitophagy. On the other hand, the reactive oxygen species (ROS) inhibitor NAC could significantly alleviate mitophagy in epithelial cells. After treatment with the mitophagy inhibitor MDIVI-1, the levels of the NLRP3 inflammasome, cleaved caspase-1, and N-gasdermin D (N-GSDMD) significantly decreased in the cells. Altogether, these results indicated that mitophagy can be triggered by ozone exposure, and subsequently induces cell death mediated by the NLRP3 inflammasome. Finally, the overexpression and knockdown of NLRP3 confirmed this conclusion. Ozone exposure induced oxidative damage, leading to mitochondrial structural and functional damage. Ozone-induced ROS triggered mitophagy through the activation of the PINK1/Parkin signaling pathway, then pyroptosis through activation of the NLRP3 inflammasome. • Ozone exposure can lead to pulmonary mitochondrial dysfunction in vivo and in vitro. • Ozone exposure can lead to mitophagy in lung, and ROS is involved in this process. • ROS induce mitophagy through the activation of the PINK1/Parkin signaling pathway. • Mitophagy induced by ozone can induce pyroptosis through the activation of NLRP3 inflammasome in lung. [ABSTRACT FROM AUTHOR]

Abstract: We report a single institution experience with total lung irradiation in 53 metastatic bone sarcoma patients in the context of two young female patients who died from treatment-induced pulmonary toxicity. A radiation dose of 19.5Gy in 1.5Gy daily fractions was given as two opposing fields with a conventional technique. Both patients succumbed within 3 months following radiotherapy. One patient had osteosarcoma whereas the other advanced Ewing's sarcoma; both with widespread metastases to the lungs at primary diagnosis. In retrospect, most likely high dose methotrexate lung toxicity observed in the osteosarcoma patient, and the GI-toxicity following pelvic radiotherapy in Ewing's case, both observed during the initial phase of their multimodal treatment, might indicate an increased individual radiosensitivity. In view of this, a review of our experience in 53 bone sarcoma patients (19 with Ewing's sarcoma and 34 with osteosarcoma) treated at our institution was conducted. We have not previously experienced significant toxicity following total lung irradiation. Among these, 42% (8/19) with Ewing's sarcoma and 9% (3/34) with osteosarcoma are long-term survivors and without clinically significant lung toxicity. [Copyright &y& Elsevier]

Abstract: Sirolimus-associated pneumonitis, a rare but serious drug-induced lung injury, has become a great concern clinically, because of the increasing use of sirolimus (rapamycin) in patients who have been subjected to solid organ transplantation. We report sirolimus-associated pneumonitis in two women who underwent renal transplantation. At variance with previous reports, the radiological findings shown on chest radiographs and computed tomography scans of the chest in these two cases were consolidation lesions mainly with minimal interstitial abnormalities. Our reported cases highlight that awareness of various radiological findings of sirolimus-associated pneumonitis is pivotal for physicians to make early diagnosis of the disorder in patients who have undergone solid organ transplantation. [Copyright &y& Elsevier]

Abstract: Carbon nanotubes (CNTs) are nanosized cylindrical hollow tubes consisting entirely of the element carbon. Currently, CNTs are playing an important role in drug delivery as a carrier system because of their several unique physical and chemical properties. Studies show that CNTs are toxic and that the extent of that toxicity depends on properties of the CNTs, such as their structure (single wall or multiple wall), length and aspects ratios, surface area, degree of aggregation, extent of oxidation, bound functional group(s), method of manufacturing, concentration, and dose. People could be exposed to CNTs either accidentally by coming in contact with the aerosol form of CNTs during production or by exposure as a result of biomedical use. Numerous in vitro and in vivo studies have shown that CNTs and/or associated contaminants or catalytic materials that arise during the production process may induce oxidative stress, prominent pulmonary inflammation, apoptosis in different cell types, and induction of cytotoxic effects on lungs. Studies on the toxicity of CNTs have mainly focused on the pulmonary effects of intratracheal or pharyngeally administered CNTs. This review examines the potential pulmonary toxicity of CNTs. From the Clinical Editor: Carbon nanotubes are promising drug delivery agents; however, their pulmonary toxicity may represent a substantial limitation to their applicability. This detailed review discusses critical aspects of the above problem. [ABSTRACT FROM AUTHOR]

Abstract: Immunomodulator therapy with the thiopurine analogues azathioprine (AZA) or 6-mercaptopurine (6-MP) is commonly prescribed for maintenance of remission in inflammatory bowel disease (IBD). Ten to twenty-five percent of patients have to withdraw from AZA or 6-MP due to adverse events that are partly explained by the relative activity of the drug metabolizing enzymes. Most of the potential major adverse events (myelosuppression, hepatotoxicity and pancreatitis) are well known. Pulmonary toxicity is rare but severe and may lead to respiratory insufficiency and even death. We describe a case of a young woman with ulcerative colitis (UC) who developed respiratory symptoms and fever combined with nodular densities and ground glass areas in both lungs on CT scan. An infection was ruled out and the diagnosis azathioprine induced pneumonitis was made. The drug was stopped and within one week her fever and respiratory symptoms resolved. Clinicians should be alert to this serious adverse event when treating patients with thiopurines. [Copyright &y& Elsevier]

Background: Fine particulate matter (PM2.5) with an aerodynamic diameter of less than 2.5 μm, exerts serious lung toxicity. At present, effective prevention measures and treatment modalities for pulmonary toxicity caused by PM2.5 are lacking. Astragaloside IV (AS-IV) is a natural product that has received increasing attention from researchers for its unique biological functions.Purpose: To investigate the protective effects of AS-IV on PM2.5-induced pulmonary toxicity and identify its potential mechanisms.Methods: The rat model of PM2.5-induced lung toxicity was created by intratracheal instillation of PM2.5 dust suspension. The investigation was performed with AS-IV or in combination with autophagic flux inhibitor (Chloroquine) or AMP-sensitive protein kinase (AMPK)-specific inhibitor (Compound C). Apoptosis was detected by terminal deoxy-nucleotidyl transferase dUTP nick end labeling (TUNEL) and western blotting. Autophagy was detected by immunofluorescence staining, autophagic flux measurement, western blotting, and transmission electron microscopy. The AMPK/mTOR pathway was analyzed by western blotting. Inflammation was analyzed by western blotting and suspension array.Results: AS-IV prevented histopathological injury, inflammation, autophagy dysfunction, apoptosis, and changes in AMPK levels induced by PM2.5. AS-IV increased autophagic flux and inhibited apoptosis and inflammation by activating the AMPK/ mammalian target of rapamycin (mTOR) pathway. However, AS-IV had no protective effect on PM2.5-induced lung injury following treatment with Compound C or Chloroquine.Conclusion: AS-IV prevented PM2.5-induced lung toxicity by restoring the balance among autophagy, apoptosis, and inflammation in rats by activating the AMPK/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract: Epidemiological studies have indicated associations between exposure to increased concentrations of ambient ultrafine particles and adverse health effects especially in susceptible individuals. To ellucidate the mechanisms underlying the findings from epidemiological studies, mice pretreated with lipopolysaccharide (LPS) (acute lung injury model) were intratracheally instilled with ultrafine carbon black particles (UFCB), and the air–blood barrier was observed to examine the translocation pathway of UFCB from the lung into the systemic circulation. In addition, lung toxicity induced by the intratracheal instillation of LPS and UFCB was studied with the use of electron microscope. LPS treatment induced acute inflammatory changes with increased number of activated macrophages and neutrophils in the degenerated alveolar walls. UFCB were demonstrated on or in the denuded basement membrane in the air–blood barrier; these findings were associated with edematous changes and fragmentation of the cytoplasms of alveolar epithelial cell type 1, and the damages of alveolar epithelial cell type 1 were frequently observed in the close vicinity of the clumps of UFCB. These findings suggest that translocation of the exposed ultrafine particles may be enhanced in the lung tissues with acute inflammatory changes. [Copyright &y& Elsevier]

Abstract: We have established and documented an in vivo bioassay for detection of hazards with intratracheally instilled fine particles, which can be used for risk assessment of toxicity of materials inhaled into deep lung tissue of humans (Yokohira et al. Establishment of a bioassay system for detection of lung toxicity due to fine particle instillation: sequential histopathological changes with acute and subacute lung damage due to intratracheal instillation of quartz in F344 male rats. J Toxicol Pathol 2005;18:13–8). For validation we here examined toxicity of fine particles from quartz, hydrotalcite, potassium octatitanate, palladium oxide and carbon black with this bioassay. A total of 108, 10-week-old F344/DuCrj male rats were randomly divided into 8 groups. Groups 1 to 5 underwent intratracheal instillation of the 5 test particles (4mg/rat) suspended in 0.2ml vehicle (saline or 10% propylene glycol and 1% sodium carboxymethyl cellulose in saline: PG-CMC) with a specially designed aerolizer, and subgroups of 7 rats were killed on Days 1 and 28 thereafter. Groups 6 and 7 similarly were exposed to saline and PG-CMC, respectively, as vehicle controls, while group 8 was maintained untreated. Using histopathological changes and immunohistochemically assessed bromodeoxyuridine (BrdU) labeling indices, inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-3 (MMP-3) levels as end points, the quartz treated group exhibited high toxicity, while the values for the other particle-treated groups pointed to only slight effects. Although additional efforts are needed to establish advantages and disadvantages with our bioassay, models featuring intratracheal instillation clearly can be useful for detection of acute or subacute lung toxicity due to inhaled fine particles by using histopathological scoring and markers like BrdU and iNOS for screening purposes in short-term studies. [Copyright &y& Elsevier]

Summary: The ameliorating effects of melatonin and vitamin C plus vitamin E were examined histologically and biochemically in lung tissues in rats exposed to chlorpyriphos-ethyl (CE). Experimental groups were as follows: Control group (C), CE treated group (CE), vitamin C plus vitamin E treated group (Vit), melatonin treated group (Mel), vitamin C plus vitamin E plus CE treated group (Vit+CE), and melatonin plus CE treated group (Mel+CE). Vitamin E and vitamin C were administered intramuscularly at the rates of 150 and 200 mg per kg body weight, respectively, in Vit and Vit+CE groups, once a day for 6 consecutive days. Melatonin was administered intramuscularly at the rate of 10 mg per kg body weight in Mel and Mel+CE groups, once a day for 6 consecutive days. At the end of the fifth day, the rats of CE, Vit+CE and Mel+CE groups were treated orally with CE dissolved in corn oil with two equal doses of 41 mg CE per kg body weight at zero and twenty-first hours. Tissue samples of lungs were taken by using appropriate techniques for biochemical and histological examinations under anesthesia at the twenty-fourth hours of CE administration, at the end of the sixth day of the experiment. In tissue homogenates, the level of thiobarbituric acid reactive substances (TBARS), antioxidant potential (AOP), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined. TBARS was significantly high (p < 0.05) in CE group compared to control group, while TBARS was found to significantly decrease (p < 0.05) with Vit and Mel groups compared to control. On the other hand, TBARS was seen to significantly decrease (p<0.05) in both groups of Vit+CE and Mel+CE compared to CE group. In comparison with CE group, SOD activity was significantly high (p < 0.05) with the groups of Vit, Mel, Vit+CE and Mel+CE. GSH-Px activity was found to significantly decrease (p < 0.05) with CE group, compared with both C and Vit groups. AOP was significantly lower (p < 0.01) in CE group than C group. Although there was an increased AOP with Vit+CE and Mel+CE groups compared to CE group, the increase in AOP was only seen to be significant (p < 0.05) in Mel+CE group. In comparison with C group, AOP significantly (p < 0.05) increased with Vit group. There was also a significant (p < 0.05) increase in AOP with Mel+CE group, compared with CE group. Additionally, AOP was significantly lower (p < 0.05) in Vit+CE group than Mel+CE group. Lungs were examined histologically at the end of sixth day. There were remarkable changes in the histomorphology of peribronchial and perivascular area in the lung of rats treated with CE. These were infiltration of mononuclear cells (such as lymphocytes, plasmocytes, macrophages), hyperplasia of type II pneumocyte, and thickened and increased connective tissue. Damage to the lung tissue such as increased inflammatory mononuclear cells in peribronchial and perivascular areas were more pronounced for the CE group than Vit+CE and Mel+CE groups in which these changes were higher than C, Vit and Mel groups. These results suggest that CE increases lipid peroxidation and decreases antioxidant enzymes activities and AOP due to increasing oxidative stress induced by CE, and high doses of vitamin C plus vitamin E and melatonin considerably reduce CE toxicity in lung tissues of rats. [Copyright &y& Elsevier]

Exposure to ambient air-borne fine particulate matter (PM 2.5) increases respiratory morbidity and mortality. The mechanisms underlying PM 2.5 -induced adverse effects remain unclear. This study aimed to uncover the molecular mechanisms of PM 2.5 -induced lung toxicity using a mouse model. Scanning electron microscopy and inductively coupled plasma mass spectrometry were used to examine and analyze PM 2.5 morphology and element compositions, respectively. Twenty four male mice were randomly divided into three groups: control (PBS), PM 2.5 (4.0 mg/kg b.w.), and PM 2.5 + Z-YVAD-FMK. In the latter group, the pan-caspase inhibitor (Z-YVAD-FMK) was intraperitoneally injected into mice at a dose of 12.5 mg/kg body weight prior to intratracheal instillation of PM 2.5 (4.0 mg/kg b.w.) every other day for a total of 3 times (n = 8 in each group). Bronchoalveolar lavage fluids (BALFs) were collected 24 h after the last instillation of PM 2.5. Levels of total proteins (TP), lactate dehydrogenase (LDH), IL-1β and IL-18 were analyzed for biomarkers of cell injury and inflammation. Additionally, histological alterations of lung tissues were assessed by hematoxylin-eosin staining. mRNA and protein expression of Caspase1, NLRP3 and GSDMD were examined by real-time fluorescent quantitative PCR and immunohistochemical staining. Exposure to PM 2.5 increased levels of TP, LDH, IL-1β, IL-18 and inflammatory cell counts in lung. The mRNA and protein expression of Caspase1, NLRP3 and GSDMD were increased. Inhibition of the NALRP3/Caspase-1 signaling pathway ameliorated PM 2.5 -induced lung injury and inflammation, partially through suppressing pyroptosis in lung. PM 2.5 exposure induces lung injury and inflammation, which is mediated by the NALRP3/Caspase-1 signaling pathway. • PM 2.5 exposure caused lung injury and inflammation in mice. • Inhibition of NALRP3/Caspase-1 signaling pathway can amelioration PM 2.5 -induced lung toxicity. • PM 2.5 exposure induced lung toxicity is related to NALRP3 inflammasome mediated macrophage pyroptosis. [ABSTRACT FROM AUTHOR]

Epidemiological studies have shown that particulate matter with an aerodynamic diameter less than 2.5 μm (PM 2.5) is closely associated with human health issues, especially pulmonary diseases such as chronic obstructive pulmonary disease (COPD), asthma and lung cancer. In this study, particles were characterized by scanning electron microscopy (SEM), microbeam energy-dispersive X-ray spectroscopy (EDS), inductively coupled plasma mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). A rat model of PM 2.5 exposure was established by nonsurgical intratracheal instillation, and the effects of biochanin A (BCA) treatment were examined. BCA showed a protective effect; it reduced PM 2.5 -induced apoptosis and the production of proinflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), and the chemokine interleukin-8 (IL-8), as measured using ELISA. These effects were accompanied by increases in the levels of antioxidant enzymes and decreases in the levels of malondialdehyde (MDA), lactate dehydrogenase (LDH) and alkaline phosphatase (AKP). Furthermore, isobaric tag for relative and absolute quantitation (iTRAQ)-based analytical techniques and bioinformatics tools were used to identify putative biomarkers, including XRCC1, MP2K5, IGJ, and F1LQ12, and the results were verified by Western blot analysis. In conclusion, our findings have scientific significance for the application of flavonoids in preventive and therapeutic strategies for PM 2.5 -associated pulmonary diseases and for the promotion of human health. Image 1 • PM 2.5 can induce oxidative stress, inflammatory response and immune regulation. • PM 2.5 induces 35 abnormal proteins expression and 4 differently expressed proteins. • Biochanin A can alleviate the PM 2.5 -induced lung toxicity in rats. [ABSTRACT FROM AUTHOR]

Chromium (Cr) is an internationally recognized carcinogenic hazard that causes serious pulmonary toxicity. However, Cr-induced pulmonary toxicity lacks effective treatment to date. Sulforaphane (SFN), a well-known organosulfur compound, has gained increasing attention because of its unique biological function. This study investigates if SFN could decrease K 2 Cr 2 O 7 -induced pulmonary toxicity and a potential mechanism involved using a rat 35-day Cr-induced pulmonary toxicity model and the mouse alveolar type II epithelial cell line (MLE-12). The results showed that SFN prevented Cr-induced oxidative stress, histopathological lesions, inflammation, apoptosis, and changes in protein kinase B (Akt) and glycogen synthase kinase 3 beta (GSK-3β) levels in vivo and in vitro. However, SFN can not play the protective effect against K 2 Cr 2 O 7 -induced cell injury after treating by an Akt-specific inhibitor (MK-2206 2HCl) in MLE-12 cells. Furthermore, SFN increased the expression of nuclear factor-E2-related factor-2 (Nrf2) phase II detoxification enzymes. Collectively, this study demonstrates that SFN prevents K 2 Cr 2 O 7 -induced lung toxicity in rats through enhancing Nrf2-mediated exogenous antioxidant defenses via activation of the Akt/GSK-3β/Fyn signaling pathway. SFN may be a novel natural substance to cure Cr-induced lung toxicity. Image 1017 • Chronic exposure of chromium (Cr) induces lung injury in rats. • Cr induces oxidative stress in the mouse alveolar type II epithelial cell line. • Oxidative stress is a key of Cr-induced lung toxicity. • Sulforaphane (SFN) relieves Cr-induced lung toxicity. • SFN prevents Cr-induced lung toxicity in rats via activation of the Akt/GSK-3β/Fyn signaling pathway. Sulforaphane prevents chromium-induced lung toxicity in rats via activation of the Akt/GSK-3β/Fyn signaling pathway. [ABSTRACT FROM AUTHOR]

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The International Agency for Research on Cancer (IARC) recently published a monograph on the evaluation of carcinogenic risks to humans of exposure to crystalline and amorphous silica particles. The IARC Working Group concluded that crystalline silica, in the form of quartz or cristobalite, from occupational sources posed a carcinogenic risk to humans (Category 1). IARC also determined that amorphous silica particles were not classifiable as to its carcinogenicity to humans (Category 3). With regard to amorphous silica, the evaluation was based primarily on the lack of toxicological and epidemiological data for these materials and this was noted in the IARC document.1 This manuscript is designed to provide a brief summary of the limited inhalation toxicity database related to amorphous silica particulatesand to cite a few studies wherein the pulmonary toxicological effects of inhaled crystalline and amorphous silica particles were compared. [ABSTRACT FROM AUTHOR]