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Background: Lungs are adversely affected by repeated exposure to thinner fumes. This study aimed to examine the pulmonary toxic effects of chronic thinner inhalation and the possible protection by chamomile administration. Adult male Wistar rats were exposed to thinner fumes for 8 weeks (4 h/day, 6 days/week), while chamomile flower extract (400 mg/kg body weight) was given orally during thinner exposure for the same period. Results: The study showed lung damage following chronic thinner exposure through increased cytochrome P2E1 (CYP2E1), superoxide anion (O2•−), hydrogen peroxide (H2O2), and malondialdehyde (MDA), with decreased antioxidant enzymes; superoxide dismutase (SOD), and catalase (CAT). Moreover, an elevation of lung enzymes; alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and lactate dehydrogenase (LDH) with depletion in total protein and albumin contents in serum and bronchoalveolar lavage fluid were observed. Thinner exposure also exhibited increased lung deoxyribonucleic acid (DNA) damage, transforming growth factor-β1 (TGF-β1), insulin-like growth factor-1 (IGF-1), hydroxyproline (HYP), and collagen type 1 (COL-1), with decreased serum surfactant protein-A (SP-A), total and differential leukocytes (WBCs) count, except for neutrophils. Histological investigations revealed deteriorative changes along with accumulated collagen fibers affecting the lung and other respiratory organs. Conclusion: Supplementation of chamomile extract succeeded in preventing thinner-induced lung oxidative stress, enzyme leakage, surfactant deficiency, DNA damage, fibrosis, and histological injury. Therefore, consumption of chamomile extract could be recommended for alleviating thinner-induced health hazards and lung toxicity. [ABSTRACT FROM AUTHOR]

Mercuric chloride (HgCl2) is extremely toxic to both humans and animals. It could be absorbed via ingestion, inhalation, and skin contact. Exposure to HgCl2 can cause severe health effects, including damages to the gastrointestinal, respiratory, and central nervous systems. The purpose of this work was to explore if carvacrol (CRV) could protect rats lungs from damage caused by HgCl2. Intraperitoneal injections of HgCl2 at a dose of 1.23 mg/kg body weight were given either alone or in conjunction with oral CRV administration at doses of 25 and 50 mg/kg body weight for 7 days. The study included biochemical and histological techniques to examine the lung tissue's oxidative stress, apoptosis, inflammation, and autophagy processes. HgCl2‐induced reductions in GSH levels and antioxidant enzymes (SOD, CAT, and GPx) activity were enhanced by CRV co‐administration. Furthermore, MDA levels were lowered by CRV. The inflammatory mediators NF‐κB, IκB, NLRP3, TNF‐α, IL‐1β, IL6, COX‐2, and iNOS were all reduced by CRV. When exposed to HgCl2, the levels of apoptotic Bax, caspase‐3, Apaf1, p53, caspase‐6, and caspase‐9 increased, but the levels of antiapoptotic Bcl‐2 reduced after CRV treatment. CRV decreased levels of Beclin‐1, LC3A, and LC3B, which in turn decreased HgCl2‐induced autophagy damage. After HgCl2 treatment, higher pathological damage was observed in terms of alveolar septal thickening, congestion, edema, and inflammatory cell infiltration compared to the control group while CRV ameliorated these effects. Consequently, by preventing HgCl2‐induced increases in oxidative stress and the corresponding inflammation, autophagy, apoptosis, and disturbance of tissue integrity in lung tissues, CRV might be seen as a useful therapeutic alternative. [ABSTRACT FROM AUTHOR]

Copyright of Farabi Medical Journal is the property of Farabi Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Selenium (Se) and zinc (Zn) are essential trace elements with antioxidant properties, and their supplementation has been shown to be protective against the toxicity of various environmental and dietary substances. The aim of this study was to investigate the potential protective effect of selenium and zinc as adjuvants against barium (Ba) toxicity in lactating rats and their offspring. The pregnant rats were divided into six groups: the first as control; group 2 received barium (67 ppm) in the drinking water; group 3 had combined Ba + Se (0.5 mg/kg) in the diet; group 4 received Zn (50 mg/kg bw) by gavage together with Ba; groups 5 and 6, positive controls, were treated with selenium (0.5 mg/kg) and zinc (50 mg/kg bw), respectively. MDA, H2O2, AOPP, CAT, GPx, and SOD levels were measured and lung histopathology was performed. Our results showed that barium administration caused lung damage as evidenced by an increase in MDA, H2O2, and AOPP levels and a decrease in the activities of CAT, GPx, and SOD in mothers and their offspring. A decrease in lung GSH, NPSH, and MT levels was also observed. Supplementation of Ba-treated rats with Se and/or Zn significantly improved the pulmonary antioxidant status of mothers and their offspring. Histopathological examinations were also consistent with the results of biochemical parameters, suggesting the beneficial role of Se and Zn supplementation, as evidenced by less accumulation of collagen fibers as studied by hematoxylin and eosin (H&E) and Masson's trichrome staining. In conclusion, we demonstrate the adverse effects of maternal barium exposure during pregnancy and on neonatal lung health and the protective effects of selenium and zinc in preventing the adverse effects of barium exposure. [ABSTRACT FROM AUTHOR]

Lead acetate (PbAc) is a compound that produces toxicity in many tissues after exposure. Sinapic acid (SNP) possesses many biological and pharmacological properties. This study aimed to investigate the efficacy of SNP on the toxicity of PbAc in lung tissue. PbAc was administered orally at 30 mg/kg and SNP at 5 or 10 mg/kg for 7 days. Biochemical, genetic, and histological methods were used to investigate inflammatory, apoptotic, endoplasmic reticulum stress, and oxidative stress damage levels in lung tissue. SNP administration induced PbAc‐reduced antioxidant (GSH, SOD, CAT, and GPx) and expression of HO‐1 in lung tissue. It also reduced MDA, induced by PbAc, and thus alleviated oxidative stress. SNP decreased the inflammatory markers NF‐κB, TNF‐α and IL‐1β levels induced by PbAc in lung tissue and exhibited anti‐inflammatory effect. PbAc increased apoptotic Bax, Apaf‐1, and Caspase‐3 mRNA transcription levels and decreased anti‐apoptotic Bcl‐2 in lung tissues. SNP decreased apoptotic damage by reversing this situation. On the other hand, SNP regulated these markers and brought them closer to the levels of the control group. PbAc caused prolonged ER stress by increasing the levels of ATF6, PERK, IRE1α, GRP78 and this activity was stopped and tended to retreat with SNP. After evaluating all the data, While PbAc caused toxic damage in lung tissue, SNP showed a protective effect by reducing this damage. [ABSTRACT FROM AUTHOR]

Metal oxide nanoparticles (MONP/s) induce DNA damage, which is influenced by their physicochemical properties. In this study, the high-throughput CometChip and micronucleus (MicroFlow) assays were used to investigate DNA and chromosomal damage in mouse lung epithelial cells induced by nano and bulk sizes of zinc oxide, copper oxide, manganese oxide, nickel oxide, aluminum oxide, cerium oxide, titanium dioxide, and iron oxide. Ionic forms of MONPs were also included. The study evaluated the impact of solubility, surface coating, and particle size on response. Correlation analysis showed that solubility in the cell culture medium was positively associated with response in both assays, with the nano form showing the same or higher response than larger particles. A subtle reduction in DNA damage response was observed post-exposure to some surface-coated MONPs. The observed difference in genotoxicity highlighted the mechanistic differences in the MONP-induced response, possibly influenced by both particle stability and chemical composition. The results highlight that combinations of properties influence response to MONPs and that solubility alone, while playing an important role, is not enough to explain the observed toxicity. The results have implications on the potential application of read-across strategies in support of human health risk assessment of MONPs. [ABSTRACT FROM AUTHOR]

Cigarette smoke induces an inflammatory response in the lungs by recruiting inflammatory cells, leading to lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Existing inhalation exposure methods for assessing the adverse effects of cigarette smoke require expensive equipment and are labor‐intensive. Therefore, we attempted to develop a novel method to assess these adverse effects using intratracheal instillation (ITI) of whole cigarette smoke condensate (WCSC). The WCSC (0, 5, 10, or 20 mg/mL) was administered by ITI once daily for 6 or 12 days using an automatic video instillator. Repeated WCSC ITI increased the lung weight, and monocyte chemoattractant protein‐1 (MCP‐1), neutrophil, and lymphocyte levels within bronchoalveolar lavage fluid compared to the control. In the histopathological analysis of the lung tissue, a mild inflammatory response was observed in the 6 and 12 days 20 mg/mL WCSC exposure groups. The genome‐wide RNA‐seq expression patterns revealed that inflammatory and immune response‐related genes, such as the chemokine signaling pathway, Th1/Th2 cell differentiation, and cytokine‐cytokine receptor interaction, were employed following WCSC exposure. In addition, MCP‐1 was time‐dependent and increased in the 10 mg/mL exposure group compared to the control group. These results suggested that the WCSC might induce the potential pulmonary inflammatory response. Furthermore, we proposed that ITI may be a rapid and effective method of evaluating the adverse effects of WCSC within a short exposure period (less than 2 weeks), and it can be used to evaluate cigarette inhalation toxicity studies as an alternative method. [ABSTRACT FROM AUTHOR]

Immune-checkpoint inhibitors have profoundly changed cancer treatment, improving the prognosis of many oncologic patients. However, despite the good efficacy of these drugs, their mechanism of action, which involves the activation of the immune system, can lead to immune-related adverse events, which may affect almost all organs. Pulmonary adverse events are relatively common, and potentially life-threatening complications may occur. The diagnosis is challenging due to the wide and non-specific spectrum of clinical and radiological manifestations. The role of the radiologist is to recognize and diagnose pulmonary immune-related adverse events, possibly even in the early stages, to estimate their extent and guide patients' management. [ABSTRACT FROM AUTHOR]

Introduction: Radiation-induced lung toxicity (RILT) is a major concern in patients who receive radiation to thorax. The purpose of the study was to evaluate the changes of pulmonary function tests (PFTs) in lung carcinoma patients treated with three-dimensional conformal radiation therapy (3-D CRT) and relation RILT with dosimetric and nondosimetric factors. Methods: This was a prospective observational study which included 65 patients of lung carcinoma treated with 3-D CRT. PFTs were assessed before the radiotherapy and at third and sixth month post-radiation therapy. Radiation pneumonitis (RP) was graded according to National Cancer Institute Common Toxicity Criteria (CTCAE) version 4.0. Results: Majority of patients already had poor lung function before commencing the radiotherapy. There was a modest decrease in pulmonary function after radiation therapy with (3-D CRT). Postradiotherapy, at third month, eight patients (12%) and at the sixth month, 16 patients (25%) were observed with Grade II RP. At the third month, the nondosimetric factors, age >65 years (P = 0.027) and pretreatment Diffusion capacity of the Lung for Carbon monoxide (DLCO) 60% (P = 0.03) were significantly related to grade ≥ II Radiation pneumonitis (RP). Among dosimetric factors, mean lung dose ≥20 Gy (P = 0.001) and volume receving 20Gy ≥35% (P = 0.05) were significantly related to grade ≥ II RP. These factors were also related to grade ≥ II RP at the sixth month with a significant P value. Conclusion: There is a progressive decrease in pulmonary function after (3-D CRT) in lung carcinoma patients. The study suggested that the baseline PFT may be utilized for the identification of high-risk patients for RILT before starting the radiotherapy in lung carcinoma. [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM2.5) is an air pollutant that causes severe lung injury. We investigated the effects of Jujuboside B (JB), a component of Zizyphi Spinosi Semen, on lung toxicity caused by PM2.5, and we identified the mechanism of its protective effect. Lung injury in an animal model was induced by intratracheal administration of a PM2.5 suspension. After 2 days of PM2.5 pretreatment, mice were administered JB via the tail vein three times over a 2-day period. JB significantly reduced the histological lung damage as well as the lung wet/dry weight ratio. JB also considerably reduced PM2.5-induced autophagy dysfunction, apoptosis, inflammatory cytokine levels, and the number of PM2.5-induced lymphocytes in the bronchial alveolar fluid. We conclude that by regulating TLR2, 4-MyD88, and mTOR-autophagy pathways, JB exerts a protective effect on lung injury. Thus, JB can be used as a potential therapeutic agent for PM2.5-induced lung damage. [ABSTRACT FROM AUTHOR]

Thermal spray coating is a process in which molten metal is sprayed onto a surface. Little is known about the health effects associated with these aerosols. Sprague-Dawley rats were exposed to aerosols (25 mg/m3 × 4 hr/d × 4 d) generated during thermal spray coating using different consumables [i.e. stainless-steel wire (PMET731), Ni-based wire (PMET885), Zn-based wire (PMET540)]. Control animals received air. Bronchoalveolar lavage was performed at 4 and 30 d post-exposure to assess lung toxicity. The particles were chain-like agglomerates and similar in size (310–378 nm). Inhalation of PMET885 aerosol caused a significant increase in lung injury and inflammation at both time points. Inhalation of PMET540 aerosol caused a slight but significant increase in lung toxicity at 4 but not 30 d. Exposure to PMET731 aerosol had no effect on lung toxicity. Overall, the lung responses were in the order: PMET885≫PMET540 >PMT731. Following a shorter exposure (25 mg/m3 × 4 h/d × 1d), lung burdens of metals from the different aerosols were determined by ICP-AES at 0, 1, 4 and 30 d post-exposure. Zn was cleared from the lungs at the fastest rate with complete clearance by 4 d post-exposure. Ni, Cr, and Mn had similar rates of clearance as nearly half of the deposited metal was cleared by 4 d. A small but significant percentage of each of these metals persisted in the lungs at 30 d. The pulmonary clearance of Fe was difficult to assess because of inherently high levels of Fe in control lungs. [ABSTRACT FROM AUTHOR]

Background: Pulmonary toxicities caused by immune checkpoint inhibitors are a prominent concern for clinicians. Clinical Practice Guidelines (CPGs) are critical for managing these toxicities. Methods: A systematic search of CPGs on checkpoint-associated pulmonary toxicities (ca-PT) was conducted in October 2022. PubMed, Embase, Cochrane Library, CINAHL, and Web of Science were searched. AGREE II and AGREE-REX were used to appraise CPGs and recommendations quality, respectively. Descriptive statistics, intraclass correlation coefficient, Kruskal-Wallis (H) test, and Spearman's correlation were used for analyses. P-values <.05 were considered statistically significant. Matrices were used to determine recommendation differences between CPGs. The study's design was based on the PRISMA 2020 checklist for systematic reviews. Protocol registration number: CRD42022358435. Results: Eight CPGs (two high-quality, three moderate-quality, and three low-quality) were identified. All CPGs covered pneumonitis. One CPG covered pleural effusions and pneumonitis/SARs-CoV-2-infection. Three CPGs covered sarcoidosis-like-reactions. CPGs for pulmonary fibrosis, airway disease, bronchiolitis, and diffuse alveolar damage, were unavailable. No CPG recommendation was based on a prospective study, and none were appraised as high-quality. Also, recommendations were not specific to histopathologic subtypes. AGREE II's "rigor of development," the domain that evaluates a guideline's methodological approach and strategies in gathering scientific evidence, correlated strongly with AGREE-REX's "overall quality" pneumonitis recommendations, r =.952; P <.01. Approximately 73% of recommendations on pneumonitis were similar between high-quality CPGs. About 16% to 74% of low-quality CPGs were similar to those recommended by high-quality CPGs. Conclusion: Prospectively designed research projects focusing on all types of ca-PT and their histopathologic subtypes are urgently needed. Due to the lack of high-quality recommendations in available CPGs, the disparities in treatment recommendations between high-quality CPGs, and the similarities in recommendations that exists between high-quality and low-quality CPGs, clinicians should thoroughly assess and responsibly appraise all available CPG recommendations in formulating treatment strategies for ca-PT. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), which is used to treat various cancers and hematological malignancies, has limited therapeutic application due to its toxicity in tissues and organs. These toxic effects occur through alterations in intracellular calcium regulation, elevated cell stress and oxidative damage, and increased apoptosis. Lercanidipine (LRD) is a long-acting antihypertensive calcium channel blocker with anti-inflammatory, anti-apoptotic, and antioxidant effects. The aim of this study was to investigate the effect of LRD on DOX-induced lung toxicity. Four groups (control, DOX, DOX + 0.5 LRD, and DOX + 2 LRD) totaling 32 rats were established. TNF-α levels in the lung tissues were detected by immunohistochemistry, and the tissues were subjected to histopathological examination. In determining oxidative stress, total antioxidant status (TAS) and total oxidative stress (TOS) were determined using spectrophotometry, and the oxidative stress index (OSI) value was calculated. The mRNA relative expression levels of the genes were evaluated by RT-qPCR. It was determined that inflammatory and oxidative stress markers and pro-apoptotic gene levels were increased and anti-apoptotic gene levels were decreased in the lung tissues of the DOX-administered group. In addition, histopathological changes were significantly increased. Although it was not statistically significant, inflammation, oxidative stress, and apoptosis were reduced, as were other histopathological indicators, in the group that received LRD (0.5 mg/kg). Inflammation, oxidative stress, and apoptosis were found to be statistically reduced and corroborated by histological findings in the group given LRD (2 mg/kg). In conclusion, it was determined that LRD had an ameliorative effect on DOX-induced lung toxicity in an experimental animal model. [ABSTRACT FROM AUTHOR]

Copper (Cu) is an essential trace element for maintaining normal homeostasis in living organisms. Yet, an elevated level of Cu beyond homeostatic capacity may lead to oxidative damage of cellular components in several organs, including the lungs. This work investigated the effects of curcumin (Curc) and nano-curcumin (nCurc) against Cu-induced lung injury, accenting the roles of oxidative stress, inflammation, and the nuclear factor erythroid 2-related factor/heme oxygenase-1 Nrf2/HO-1 pathway. Rats were challenged with 100 mg/kg of copper sulfate (CuSO4) while being treated with Curc or nCurc for 7 days. Cu-triggered lung oxidative stress detected as dysregulation of oxidative/antioxidant markers, a downregulation of Nrf-2/HO-1 signaling, and an increase in the inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and intracellular adhesion molecule-1 (ICAM-1). Additionally, it decreased the expression of lung-specific proteins, surfactant protein-C (SP-C), and mucin-1 (MUC-1), induced apoptosis, and caused changes in lung histology. Curc and nCurc alleviated CuSO4-induced lung injury by suppressing oxidative damage and inflammation and activating Nrf-2/HO-1. They also prevented apoptosis and restored the normal expression of SP-C and MUC-1. We concluded that nCurc exhibited superior efficacy compared with Curc in mitigating CuSO4-induced lung injury. This was associated with reduced oxidative stress, inflammation, and apoptotic responses and increased Nrf2/HO-1 signaling and expression of SP-C and MUC-1. [ABSTRACT FROM AUTHOR]

Background: The optimal strategy for the treatment of recurrent and/or advanced endometrial cancer is still undefined. Recently, despite the lack of any predictive biomarker, the combination of pembrolizumab with lenvatinib has improved survival outcomes. We here report the long-term management of lung toxicity in a patient with endometrial cancer, and we critically review the current therapeutic options for this disease. Results: A patient with heavily pretreated endometrial cancer took pembrolizumab plus lenvatinib for 1 year, achieving a persistent partial response with a time to treatment failure of 18 months, despite relevant lung toxicity that did not affect the remarkable overall clinical benefit. A systematic review of this combination underlines the efficacy outcome despite toxicity. Interestingly, the literature review on lung toxicity suggested the role of antiangiogenetic agents in the pathogenesis of lung cavitation, probably related to direct treatment activity, and disclosed a potential radiological sign predictive of the activity of anti-angiogenetic agents. Conclusion: We underline the efficacy of pembrolizumab plus lenvatinib in the current treatment landscape of endometrial cancer, underscoring the relevance of a correct management of toxicity. [ABSTRACT FROM AUTHOR]

Objectives: Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK TKIs) have shown remarkable clinical activity in patients with non‐small‐cell lung cancer (NSCLC). However, pneumonitis is a serious side effect of ALK TKIs in NSCLC patients. In this meta‐analysis, we aimed to determine the incidence of ALK‐TKI‐associated pneumonitis. Materials and Methods: We searched electronic databases to identify relevant studies published until August 2022. The incidence of pneumonitis was calculated using a fixed‐effects model when no substantial heterogeneity was observed. Otherwise, a random‐effects model was used. Subgroup analyses of different treatment groups were performed. Statistical analyses were conducted using STATA 17.0. Results: Twenty‐six clinical trials involving 4752 patients were eligible for analysis. All‐grade pneumonitis incidence was 2.92% (95% confidence interval [CI]: 1.79%–4.27%), high‐grade (Grade 3–4) pneumonitis incidence was 1.42% (95% CI: 0.84%–2.12%) and Grade 5 pneumonitis incidence was 0.09% (95% CI: 0.00%–0.28%). The subgroup analysis showed that brigatinib was associated with the highest incidence of both all‐grade and high‐grade pneumonitis (7.09% and 3.06%, respectively). ALK TKI treatment after chemotherapy was associated with a higher incidence of all‐grade and high‐grade pneumonitis than first‐line ALK TKI treatment (7.73% vs. 2.26% and 3.64% vs. 1.26%, respectively). Cohorts from Japanese trials had a higher incidence of all‐grade and high‐grade pneumonitis. Conclusion: Our study provides precise data on the incidence of pneumonitis in patients receiving treatment with ALK TKIs. Overall, ALK TKIs have tolerable pulmonary toxicity. Early pneumonitis identification and treatment are required to prevent further deterioration in patients receiving treatment with brigatinib and in those who received prior chemotherapy, particularly in the Japanese population. [ABSTRACT FROM AUTHOR]

This study characterized and investigated the toxicity of two multi-walled carbon nanotubes (MWCNT) NM-401 and NM-403 at 60 and 180 µg after four repeated intratracheal instillations; follow-up times were 3, 7, 30, and 90 days after the last instillation. NM-401 was needle-like, long, and thick, while NM-403 was entangled, short, and thin. Both MWCNT types induced transient pulmonary and systemic alterations in renal function and oxidative lipid damage markers in recent times. Animals showed general toxicity in the immediate times after exposures, in addition to increased pulmonary LDH release at day 3. In further times, decreased liver and kidney relative weights were noted at higher MWCNT doses. Lung histological damages included pulmonary fibrosis, for both MWCNT types, similarly to asbestos; single liver and kidney histological alterations were present. Repeated instillations led to persistent pulmonary damage at low doses, and possibly the extrapulmonary effects may be associated with the consecutive exposures. [ABSTRACT FROM AUTHOR]

Copyright of Praxis (16618157) is the property of Aerzteverlag medinfo AG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

E-cigarette consumption is under scrutiny by regulatory authorities due to concerns about product toxicity, lack of manufacturing standards, and increasing reports of e-cigarette- or vaping-associated acute lung injury. In vitro studies have demonstrated cytotoxicity, mitochondrial dysfunction, and oxidative stress induced by unflavored e-cigarette aerosols and flavoring additives. However, e-cigarette effects on the complex lung parenchyma remain unclear. Herein, the impact of e-cigarette condensates with or without menthol flavoring on functional, structural, and cellular responses was investigated using mouse precision cut lung slices (PCLS). PCLS were exposed to e-cigarette condensates prepared from aerosolized vehicle, nicotine, nicotine + menthol, and menthol e-fluids at doses from 50 to 500 mM. Doses were normalized to the glycerin content of vehicle. Video-microscopy of PCLS revealed impaired contractile responsiveness of airways to methacholine and dampened ciliary beating following exposure to menthol-containing condensates at concentrations greater than 300 mM. Following 500 mM menthol-containing condensate exposure, epithelial exfoliation in intrabronchial airways was identified in histological sections of PCLS. Measurement of lactate dehydrogenase release, mitochondrial water-soluble-tetrazolium salt-1 conversion, and glutathione content supported earlier findings of nicotine or nicotine + menthol e-cigarette-induced dose-dependent cytotoxicity and oxidative stress responses. Evaluation of PCLS metabolic activity revealed dose-related impairment of mitochondrial oxidative phosphorylation and glycolysis after exposure to menthol-containing condensates. Taken together, these data demonstrate prominent mentholinduced pulmonary toxicity and impairment of essential physiological functions in the lung, which warrants concerns about e-cigarette consumer safety and emphasizes the need for further investigations of molecular mechanisms of toxicity and menthol effects in an experimental model of disease. [ABSTRACT FROM AUTHOR]

The detection of high levels of microplastics in indoor and outdoor air has increased concerns regarding its toxic effects on the respiratory system. They are not easily degradable and can be deposited deep in the lungs. Although several studies have reported inhalation toxicities of microplastics, they are still controversial due to a lack of evidence. Herein, we evaluated the inhalation toxicities of three differently charged polystyrene microplastics (PS‐MPs), the most abundant microplastics in the air. Cytotoxicity and ROS generation were evaluated using WST‐1 and DCF‐DA assays, respectively. To evaluate the toxic effects on the lung, inflammatory responses were analyzed after repeated exposure to the PS‐MPs through intratracheal instillation. To explore the mechanism of toxicity, autophagy and ER stress‐associated proteins were analyzed. Only the positively charged PS‐MPs (NH2‐PS‐MPs) showed cytotoxicity and increased ROS generation in BEAS‐2B cells. Similarly, only NH2‐PS‐MPs significantly increased the expression and secretion of the pro‐inflammatory cytokine IL‐β in the animal experiments. The expression of ER stress proteins indicated that NH2‐PS‐MPs increased ER stress via PERK‐EIF2α and ATF4‐CHOP pathways. Moreover, accumulation of NH2‐PS‐MPs in lysosomes and deformity of the nucleus were observed in BEAS‐2B cells with autophagy induction. Taken together, our results demonstrated that NH2‐PS‐MPs induced autophagic cell death in bronchial epithelial cells, leading to inflammatory responses in the lungs. These results suggest that repeated inhalation of microplastics can result in inflammatory responses in the lung through cellular damage of lung epithelial cells, and that inhalation microplastics should be monitored to reduce inhalation health risks. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pulmonary toxicities caused by immune checkpoint inhibitors are a prominent concern for clinicians. Clinical Practice Guidelines (CPGs) are critical for managing these toxicities. METHODS: A systematic search of CPGs on checkpoint-associated pulmonary toxicities (ca-PT) was conducted in October 2022. PubMed, Embase, Cochrane Library, CINAHL, and Web of Science were searched. AGREE II and AGREE-REX were used to appraise CPGs and recommendations quality, respectively. Descriptive statistics, intraclass correlation coefficient, Kruskal-Wallis (H) test, and Spearman's correlation were used for analyses. P-values < .05 were considered statistically significant. Matrices were used to determine recommendation differences between CPGs. The study's design was based on the PRISMA 2020 checklist for systematic reviews. Protocol registration number: CRD42022358435. RESULTS: Eight CPGs (two high-quality, three moderate-quality, and three low-quality) were identified. All CPGs covered pneumonitis. One CPG covered pleural effusions and pneumonitis/SARs-CoV-2-infection. Three CPGs covered sarcoidosis-like-reactions. CPGs for pulmonary fibrosis, airway disease, bronchiolitis, and diffuse alveolar damage, were unavailable. No CPG recommendation was based on a prospective study, and none were appraised as high-quality. Also, recommendations were not specific to histopathologic subtypes. AGREE II's "rigor of development," the domain that evaluates a guideline's methodological approach and strategies in gathering scientific evidence, correlated strongly with AGREE-REX's "overall quality" pneumonitis recommendations, r = .952; P < .01. Approximately 73% of recommendations on pneumonitis were similar between high-quality CPGs. About 16% to 74% of low-quality CPGs were similar to those recommended by high-quality CPGs. CONCLUSION: Prospectively designed research projects focusing on all types of ca-PT and their histopathologic subtypes are urgently needed. Due to the lack of high-quality recommendations in available CPGs, the disparities in treatment recommendations between highquality CPGs, and the similarities in recommendations that exists between high-quality and low-quality CPGs, clinicians should thoroughly assess and responsibly appraise all available CPG recommendations in formulating treatment strategies for ca-PT. [ABSTRACT FROM AUTHOR]

Purpose: A major complication of sequential and concomitant chemoradiation in breast cancer treatment is interstitial pneumonitis induced by radiation therapy (RT), systemic therapy, or a combination of both. Dose and volume of co-irradiated lung tissue directly correlate with the risk of radiation pneumonitis. Especially in case of combined treatment, it is often unclear which of the used therapeutic agents promote pneumonitis. Methods: This was a prospective monocentric study including 396 breast cancer patients. A systematic analysis of single and combined therapeutic measures was performed in order to identify treatment-related factors enhancing the risk of pneumonitis post RT. Results: Overall incidence of pneumonitis of any grade was 38%; 28% were asymptomatic (grade 1) and 10% were symptomatic (> grade 1). Pneumonitis > grade 2 did not occur. Beside age, smoking status, and mean lung dose, the combined treatment with goserelin and tamoxifen significantly enhanced the risk of pneumonitis in a supra-additive pattern (odds ratio [OR] 4.38), whereas each agent alone or combined with other drugs only nonsignificantly contributed to a higher pneumonitis incidence post RT (OR 1.52 and OR 1.16, respectively). None of the other systemic treatments, including taxanes, increased radiation pneumonitis risk in sequential chemoradiation. Conclusion: Common treatment schedules in sequential chemoradiation following breast-conserving surgery only moderately increase lung toxicity, mainly as an asymptomatic complication, or to a minor extent, as transient pneumonitis ≤ grade 2. However, combined treatment with tamoxifen and the LHRH analog goserelin significantly increased the risk of pneumonitis in breast cancer patients after chemoradiation. Thus, closer surveillance of involved patients is advisable. [ABSTRACT FROM AUTHOR]

The present study aimed to develop fast melting tablets (FMTs) using silymarin (SM) owing to FMTs rapid disintegration and dissolution. FMTs represent a pathway to help patients to increase their compliance level of treatment via facile administration without water or chewing beside reduction cost. One of the methods for FMTs formulation is lyophilization. Optimization of SM-FMTs was developed via a 32 factorial design. All prepared SM-FMTs were evaluated for weight variation, thickness, breaking force, friability, content uniformity, disintegration time (DT), and % SM released. The optimized FMT formula was selected based on the criteria of scoring the fastest DT and highest % SM released after 10 min (Q10). Optimized FMT was subjected to Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) besides investigating its lung-protective efficacy. All SM-FMT tablets showed acceptable properties within the pharmacopeial standards. Optimized FMT (F7) scored a DT of 12.5 ± 0.64 Sec and % SM released at Q10 of 82.69 ± 2.88%. No incompatibilities were found between SM and excipients, it showed a porous structure under SEM. The optimized formula decreased cytokines, up-regulated miRNA133a, and down-regulated miRNA-155 and COX-2 involved in the protection against lung toxicity prompted by HgCl2 in a manner comparable to free SM at the same dosage. [ABSTRACT FROM AUTHOR]

Thermal spray coating is an industrial process in which molten metal is sprayed at high velocity onto a surface as a protective coating. An automated electric arc wire thermal spray coating aerosol generator and inhalation exposure system was developed to simulate an occupational exposure and, using this system, male Sprague–Dawley rats were exposed to stainless steel PMET720 aerosols at 25 mg/m3 × 4 h/day × 9 day. Lung injury, inflammation, and cytokine alteration were determined. Resolution was assessed by evaluating these parameters at 1, 7, 14 and 28 d after exposure. The aerosols generated were also collected and characterized. Macrophages were exposed in vitro over a wide dose range (0–200 µg/ml) to determine cytotoxicity and to screen for known mechanisms of toxicity. Welding fumes were used as comparative particulate controls. In vivo lung damage, inflammation and alteration in cytokines were observed 1 day post exposure and this response resolved by day 7. Alveolar macrophages retained the particulates even after 28 day post-exposure. In line with the pulmonary toxicity findings, in vitro cytotoxicity and membrane damage in macrophages were observed only at the higher doses. Electron paramagnetic resonance showed in an acellular environment the particulate generated free radicals and a dose-dependent increase in intracellular oxidative stress and NF-kB/AP-1 activity was observed. PMET720 particles were internalized via clathrin and caveolar mediated endocytosis as well as actin-dependent pinocytosis/phagocytosis. The results suggest that compared to stainless steel welding fumes, the PMET 720 aerosols were not as overtly toxic, and the animals recovered from the acute pulmonary injury by 7 days. [ABSTRACT FROM AUTHOR]

Ultrafine particulate matter with less than 2.5 μm diameter (PM2.5) is an air pollutant that causes severe lung damage. Currently, effective treatment and preventive methods for PM2.5-induced lung damage are limited. Cirsilineol (CSL) is a small natural compound isolated from Artemisia vestita. In this study, the efficacy of CSL on PM2.5-induced lung toxicity was tested, and its mechanism was identified. Lung injury was caused by intratracheal administration of PM2.5 suspension in animal models. Two days after PM2.5 pretreatment, CSL was injected via mouse tail vein for two days. The effects of CSL on PM2.5-induced lung damage, autophagy, apoptosis, and pulmonary inflammation in a mouse model and their mechanisms were investigated. CSL significantly suppressed histological lung damage and lung wet/dry weight proportion. CSL also significantly reduced PM2.5-induced autophagy dysfunction, apoptosis, lymphocyte suppression, and inflammatory cytokine levels in bronchoalveolar fluid (BALF). Furthermore, CSL increased mammalian target of rapamycin (mTOR) phosphorylation and significantly inhibited the expression of Toll-like receptors (TLR) 2 and 4, MyD88, and the autophagy proteins, Beclin1 and LC3II. Thus, CSL exerts protective effects on pulmonary damage by regulating mTOR and TLR2,4–myD88 autophagy pathways. Therefore, CSL can be used as an effective treatment for PM2.5-induced lung damage. [ABSTRACT FROM AUTHOR]

Cypermethrin (CYP), a type II synthetic pyrethroid, is the most widely used insecticide worldwide. Inhalation of it may cause side effects. This study is aimed to examine potential protection of quercetin (QUE) which is a well‐known antioxidant in CYP‐induced lung toxicity. Accordingly, 35 Spraque Dawley male rats were divided into five equal groups as follows: I‐Control group, II‐QUE group (50 mg/kg/b.w. QUE), III‐CYP group (25 mg/kg/b.w. CYP), IV‐CYP + QUE 25 (25 mg/kg/b.w. CYP + 25 mg/kg/b.w. QUE), V‐CYP + QUE (25 mg/kg/b.w. CYP + 50 mg/kg/b.w. QUE) were treated with oral gavage throughout 28 days. CYP intoxication was associated with increased malondialdehyde level while glutathione concentration, activities of glutathione peroxidase, superoxide dismutase, and catalase reduced. CYP adminisitration caused of apoptosis in the lung by up‐regulating caspase‐3 and Bax levels and down‐regulating Bcl‐2. CYP also caused of endoplasmic reticulum (ER) stress by increasing mRNA transcript levels of PERK, IRE1, ATF6, and GRP78. Additionally, it was observed that CYP administration activated IL‐6/JAK2/STAT3/MAPK14 signaling pathway and levels of IL‐1β, NF‐κB, TNF‐α, and iNOS in the lung tissue. Therefore, it was determined that CYP administration triggered autophagy by upregulating LC3A and LC3B mRNA transcript levels. Moreover, the protein levels of NF‐κB, caspase‐3, Bax, Bcl‐2, and cytochorme‐c were examined by Western blot analysis. However, co‐treatment with QUE at a dose of 25 and 50 mg/kg considerably protective oxidative stress, inflammation, apoptosis, ER stress, autophagy, and IL‐6/JAK2/STAT3/MAPK14 signaling pathway in lung tissue. Overall, the findings of this study suggest that lung damage associated with CYP toxicity could be protected by QUE administration. [ABSTRACT FROM AUTHOR]

Ga-68 labeled prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) is increasingly recognized as the best imaging modality for disease staging and detection of recurrent prostate cancer. Despite its name, PSMA expression has been reported in the neovasculature of several nonprostatic benign and malignant pathologies. Docetaxel, a taxane antineoplastic agent, is the mainstay of treatment in castration-resistant prostate cancer and high-volume hormone-sensitive prostate cancer. Although the occurrence of docetaxel-related interstitial lung disease is rare, it may lead to respiratory failure if treatment is delayed. We present a case of metastatic castration-resistant prostate cancer, wherein docetaxel-induced interstitial pneumonitis was detected on Ga-68 PSMA PET/CT after docetaxel administration. [ABSTRACT FROM AUTHOR]

Background and Objective: The study aims to evaluate the histopathological changes, enzymatic alterations, and DNA damage in rat lungs induced by whole-body gamma irradiation as well as evaluation of the protective effect of pycnogenol.Materials and Methods: A hundred adult male rats were equally divided into ten groups including control, four antioxidants, γ-irradiation, four antioxidant + γ-irradiations. This study began the day before radiation treatment and continued for 3 days. The pycnogenol was dissolved 5% dimethyl sulfoxide and then administered orally through a gastric tube at a dose of 37.5 mg/kg, 75 mg/kg, 150 mg/kg, and 300 mg/kg in 24, 48, and 72 h before irradiation. Irradiation was applied with a whole-body irradiation dose of 900 cGy in one fraction. DNA damage, histopathological changes, catalase (CAT), and superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in lung tissue of rats were evaluated 3 days after irradiation.Results: CAT and SOD activities were found to be significantly lower in the irradiation group than control (P < 0.001). CAT and SOD activities were higher in the antioxidant + γ-irradiation group than both irradiation and control groups. MDA levels were significantly higher in the irradiation group compared to control (P < 0.001), whereas MDA levels decreased in the antioxidant + γ-irradiation group compared to the irradiation group. The antioxidant groups were significantly increased comet parameters depend on pycnogenol doses compared to control. The antioxidant + γ-irradiation was decreased comet parameter compared to γ-irradiation. As a result of the histopathologically, the antioxidant groups were different than the control group that in the areas of alveolar sacs and connective tissue areas were seen hemorrhage areas similar to the irradiation group.Conclusion: We demonstrate that 300 mg/kg of pycnogenol might provide significant protection against deleterious effects from whole-body ionizing radiation on the lung tissue. P300+ γ-ray group was significantly reduced radiation-induced lung injury and was possible to observe significantly preservation. [ABSTRACT FROM AUTHOR]

Inhaled toxic chemicals and particulates are known to disrupt lung homeostasis causing pulmonary toxicity and tissue injury. However, biomarkers of such exposures and their underlying mechanisms are poorly understood, especially for emerging toxicants such as engineered nanoparticles and chemical threat agents such as chlorine gas (Cl2). Aquaporins (AQPs), commonly referred to as water channels, are known to play roles in lung homeostasis and pathophysiology. However, little is known on their regulation in toxicant-induced lung injuries. Here, we compared four lung toxicity models namely, acute chemical exposure (Cl2)-, chronic particulate exposure (carbon nanotubes/CNT)-, chronic chemical exposure (cigarette smoke extract/CSE)-, and a chronic co-exposure (CNT + CSE)- model, for modulation of lung aquaporins (AQPs 1, 3, 4, and 5) in relation to other pathophysiological endpoints. These included markers of compromised state of lung mucosal lining [mucin 5b (MUC5B) and surfactant protein A (SP-A)] and lung-blood barrier [protein content in bronchoalveolar lavage (BAL) fluid and, cell tight junction proteins occludin and zona-occludens]. The results showed toxicity model-specific regulation of AQPs measured in terms of mRNA abundance. A differential upregulation was observed for AQP1 in acute Cl2 exposure model (14.71-fold; p = 0.002) and AQP3 in chronic CNT exposure model (3.83-fold; p = 0.044). In contrast, AQP4 was downregulated in chronic CSE model whereas AQP5 showed no significant change in any of the models. SP-A and MUC5B expression showed a decreasing pattern across all toxicity models except the acute Cl2 toxicity model, which showed a highly significant upregulation of MUC5B (25.95-fold; p = 0.003). This was consistent with other significant pathophysiological changes observed in this acute model, particularly a compromised lung epithelial-endothelial barrier indicated by significantly increased protein infiltration and expression of tight junction proteins, and more severe histopathological (structural and immunological) changes. To our knowledge, this is the first report on lung AQPs as molecular targets of the study toxicants. The differentially regulated AQPs, AQP1 in acute Cl2 exposure versus AQP3 in chronic CNT nanoparticle exposure, in conjunction with the corresponding differentially impacted pathophysiological endpoints (particularly MUC5B) could potentially serve as predictive markers of toxicant type-specific pulmonary injury and as candidates for future investigation for clinical intervention. [ABSTRACT FROM AUTHOR]

Acrylamide (ACR) has genotoxic, neurotoxic, and carcinogenic effects. From past to present, various plants or their products have been used for therapeutic purposes such as morin. It was aimed to detect possible protective effects of morin vs ACR‐induced lung toxicity. The rats, treated with ACR alone or with morin for 10 consecutive days, were included in the study. A broad variety of biomarkers related to oxidative stress, apoptosis, autophagy, and inflammatory responses were evaluated. ACR increased malondialdehyde (MDA), tumor necrosis factor‐alpha (TNF‐α), cyclooxygenase‐2 (COX‐2), nuclear factor kappa‐B (NF‐κB), Beclin‐1, IL‐1β, bcl‐2 associated X protein (Bax), caspase‐3, light chain 3‐A (LC3‐A), and light chain 3‐B (LC3‐B) levels but reduced mammalian target of rapamycin (mTOR), b‐cell lymphoma‐2 (Bcl‐2), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione (GSH) in lung tissues. The morin had effects on the level of these molecules in a way that is opposite to ACR. While ACR‐induced oxidative stress, apoptotic, autophagic, inflammatory responses, and may cause pulmonary dysfunction, the morin reduced ACR‐induced lung damage. Practical applications: ACR is a toxic chemical produced by frying, baking, roasting, or grilling foods with high starch content and has genotoxic, neurotoxic, and carcinogenic effects. As an antioxidant compound, the morin is obtained from plants or their products. It was aimed to detect possible protective effects of morin against ACR‐induced lung toxicity. It was detected that ACR‐induced oxidative stress, apoptotic, autophagic, inflammatory responses, and may cause pulmonary dysfunction, but the morin reduced ACR‐induced lung damage. [ABSTRACT FROM AUTHOR]

Introduction. Amiodarone is often used in the treatment of arrhythmias. Despite its undoubtedly excellent antiarrhythmic effect, its use can also causa serious adverse effects. This case report presents a patient who, after several months of treatment with amiodarone, developed severe pulmonary complications and transient liver injury. Despite discontinuation of the drug and implementation of optimal treatment aimed at harm reduction, a full resolution of the pulmonary lesions was not achieved. Objective. The aim of the report is to draw attention to the risks to the respiratory system associated with the use of amiodarone. It is worth noting that some symptoms of post-amiodarone lung damage may resemble the exacerbation of heart failure, which contributes to the delay of a correct diagnosis and prolongs the time to the start treatment. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the molecular mechanisms underlying the pulmonary toxicity induced by exposure to one form of multi-walled carbon nanotubes (MWCNT-7). Materials and methods: Rats were exposed, by whole-body inhalation, to air or an aerosol containing MWCNT-7 particles at target cumulative doses (concentration x time) ranging from 22.5 to 180 (mg/m3)h over a three-day (6 hours/day) period and toxicity and global gene expression profiles were determined in the lungs. Results: MWCNT-7 particles, associated with alveolar macrophages (AMs), were detected in rat lungs following the exposure. Mild to moderate lung pathological changes consisting of increased cellularity, thickening of the alveolar wall, alveolitis, fibrosis, and granuloma formation were detected. Bronchoalveolar lavage (BAL) toxicity parameters such as lactate dehydrogenase activity, number of AMs and polymorphonuclear leukocytes (PMNs), intracellular oxidant generation by phagocytes, and levels of cytokines were significantly (p < 0.05) increased in response to exposure to MWCNT-7. Global gene expression profiling identified several significantly differentially expressed genes (fold change >1.5 and FDR p value <0.05) in all the MWCNT-7 exposed rats. Bioinformatic analysis of the gene expression data identified significant enrichment of several diseases/biological function categories (for example, cancer, leukocyte migration, inflammatory response, mitosis, and movement of phagocytes) and canonical pathways (for example, kinetochore metaphase signaling pathway, granulocyte and agranulocyte adhesion and diapedesis, acute phase response, and LXR/RXR activation). The alterations in the lung toxicity parameters and gene expression changes exhibited a dose-response to the MWCNT exposure. Conclusions: Taken together, the data provided insights into the molecular mechanisms underlying the pulmonary toxicity induced by inhalation exposure of rats to MWCNT-7. [ABSTRACT FROM AUTHOR]

Nanomaterials (NMs) solve specific problems with remarkable results in several industrial and scientific areas. Among NMs, silver nanoparticles (AgNPs) have been extensively employed as drug carriers, medical diagnostics, energy harvesting devices, sensors, lubricants, and bioremediation. Notably, they have shown excellent antimicrobial, anticancer, and antiviral properties in the biomedical field. The literature analysis shows a selective cytotoxic effect on cancer cells compared to healthy cells, making its potential application in cancer treatment evident, increasing the need to study the potential risk of their use to environmental and human health. A large battery of toxicity models, both in vitro and in vivo, have been established to predict the harmful effects of incorporating AgNPs in these numerous areas or those produced due to involuntary exposure. However, these models often report contradictory results due to their lack of standardization, generating controversy and slowing the advances in nanotoxicology research, fundamentally by generalizing the biological response produced by the AgNP formulations. This review summarizes the last ten years' reports concerning AgNPs' toxicity in cellular respiratory system models (e.g., mono-culture models, co-cultures, 3D cultures, ex vivo and in vivo). In turn, more complex cellular models represent in a better way the physical and chemical barriers of the body; however, results should be used carefully so as not to be misleading. The main objective of this work is to highlight current models with the highest physiological relevance, identifying the opportunity areas of lung nanotoxicology and contributing to the establishment and strengthening of specific regulations regarding health and the environment. [ABSTRACT FROM AUTHOR]

Background: Although rare, taxane-induced interstitial pneumonitis is a well-recognized toxicity following chemotherapy. Data on taxane rechallenge in patients who developed taxane-induced interstitial pneumonitis following chemotherapy are limited. Here, we share our experience of acute interstitial pneumonitis following taxane chemotherapy for breast cancer and its clinical outcome following steroids and subsequent rechallenge with taxanes in selected patients without residual lung abnormalities on imaging following steroid treatment. Objectives: To study the taxane-induced acute interstitial pneumonitis in patients with breast cancer receiving chemotherapy and outcome of taxane rechallenge in these patients. Materials and Methods: Patients with breast cancer who developed taxane-induced acute interstitial pneumonitis following chemotherapy either with paclitaxel or docetaxel were included. Results: Among 1240 patients with breast cancer, who received chemotherapy with either docetaxel or paclitaxel, 41 patients developed taxane-induced acute interstitial lung disease (ILD) during the study period. The interstitial pneumonitis was more seen with docetaxel. Among paclitaxel regimens, weekly schedules showed more cases of ILD than 2 weekly paclitaxel. After steroid pulse/maintenance treatment, complete resolution of lung abnormalities was seen in 76%, but residual interstitial pattern on imaging was noted in 24% of patients. Taxane rechallenge was done in 20 (49%) patients. Agents used were paclitaxel, nab-paclitaxel, or docetaxel. All rechallenged patients received short-course oral steroids for one week following taxane rechallenge as a safety measure. Rechallenge was not done in 51% either due to patient unwillingness for rechallenge (27%) or patient with residual interstitial pattern on imaging (24%). None of the patients experienced any recurrence of pneumonitis or any mortality following taxane rechallenge. Conclusion: Acute interstitial pneumonitis is a well-known toxicity following taxanes in breast cancer and taxane rechallenge is an option in those patients without any residual pneumonitis following steroid pulse/maintenance. We also advise short-course oral steroids for 1 week following taxane rechallenge as a safety measure. We strongly do not recommend rechallenge in patients with residual lung abnormalities after steroids. [ABSTRACT FROM AUTHOR]

Background: The potential protective properties of carvacrol (CRV), which possesses various biological and pharmacological properties, against lung toxicity caused by cadmium (Cd), a major environmental pollutant, were investigated in the present study. Methods and results: In the study, rats were given 25 or 50 mg/kg CRV orally 30 min after administrating 25 mg/kg cadmium chloride for seven days. Subsequently, the levels of 8-OHdG, MMP-2, and MMP-9, as well as markers of oxidative stress, inflammation, and apoptosis, were analyzed in the lung tissue of the animals. The results revealed that CRV exhibited antioxidant characteristics and raised SOD, CAT, GPx, and CAT levels and decreased the MDA levels induced by Cd. It also suppressed proinflammatory cytokines by lowering the levels of CRV NF-κB and p38 MAPK, thus exerting an anti-inflammatory effect against Cd. It was found that the levels of Bax, Caspase-3, and cytochrome c increased by Cd were decreased by the application of CRV. CRV also showed an anti-apoptotic effect by increasing Bcl-2 levels. The levels of 8-OHdG, MMP2, and MMP9, which increased with Cd administration, were observed to reduce after treatment with CRV. Conclusions: The results indicate that CRV has protective properties against Cd-induced lung toxicity. [ABSTRACT FROM AUTHOR]

Background: Open burning of anthropogenic sources can release hazardous emissions and has been associated with increased prevalence of cardiopulmonary health outcomes. Exposure to smoke emitted from burn pits in military bases has been linked with respiratory illness among military and civilian personnel returning from war zones. Although the composition of the materials being burned is well studied, the resulting chemistry and potential toxicity of the emissions are not. Methods: Smoke emission condensates from either flaming or smoldering combustion of five different types of burn pit-related waste: cardboard; plywood; plastic; mixture; and mixture/diesel, were obtained from a laboratory-scale furnace coupled to a multistage cryotrap system. The primary emissions and smoke condensates were analyzed for a standardized suite of chemical species, and the condensates were studied for pulmonary toxicity in female CD-1 mice and mutagenic activity in Salmonella (Ames) mutagenicity assay using the frameshift strain TA98 and the base-substitution strain TA100 with and without metabolic activation (S9 from rat liver). Results: Most of the particles in the smoke emitted from flaming and smoldering combustion were less than 2.5 µm in diameter. Burning of plastic containing wastes (plastic, mixture, or mixture/diesel) emitted larger amounts of particulate matter (PM) compared to other types of waste. On an equal mass basis, the smoke PM from flaming combustion of plastic containing wastes caused more inflammation and lung injury and was more mutagenic than other samples, and the biological responses were associated with elevated polycyclic aromatic hydrocarbon levels. Conclusions: This study suggests that adverse health effects of burn pit smoke exposure vary depending on waste type and combustion temperature; however, burning plastic at high temperature was the most significant contributor to the toxicity outcomes. These findings will provide a better understanding of the complex chemical and combustion temperature factors that determine toxicity of burn pit smoke and its potential health risks at military bases. [ABSTRACT FROM AUTHOR]

Copyright of Rassegna di Patologia dell'Apparato Respiratorio is the property of AIPO - Associazione Italiana Pneumologi Ospedalieri and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Pulmonary toxicity is documented in long‐term survivors of allogeneic BMT. No studies have specifically evaluated late pulmonary symptomatology in these patients. 85 long‐term pediatric survivors were sent a validated questionnaire of pulmonary symptomatology. Demographic and clinical data were retrospectively collected from the respondents medical records. Response rate was 52.9%. Mean follow‐up post‐BMT of those who responded was 12.3 years. Mean pulmonary symptom scores were low (0.78). There was no significant difference in symptoms between patients who underwent MA conditioning with or without TBI. These results are reassuring that long‐term survivors of pediatric BMT have few respiratory symptoms which do not impact on activities of daily living. [ABSTRACT FROM AUTHOR]

The primary objective is to evaluate the potential dosimetric gains of performing functional avoidance‐based proton treatment planning using 4DCT derived ventilation imaging. 4DCT data of 31 patients from a prospective functional avoidance clinical trial were evaluated with intensity modulated proton therapy (IMPT) plans and compared with clinical volumetric modulated arc therapy (VMAT) plans. Dosimetric parameters were compared between standard and functional plans with IMPT and VMAT with one‐way analysis of variance and post hoc paired student t‐test. Normal Tissue Complication Probability (NTCP) models were employed to estimate the risk of two toxicity endpoints for healthy lung tissues. Dose degradation due to proton motion interplay effect was evaluated. Functional IMPT plans led to significant dose reduction to functional lung structures when compared with functional VMAT without significant dose increase to Organ at Risk (OAR) structures. When interplay effect is considered, no significant dose degradation was observed for the OARs or the clinical target volume (CTV) volumes for functional IMPT. Using fV20 as the dose metric and Grade 2+ pneumonitis as toxicity endpoint, there is a mean 5.7% reduction in Grade 2+ RP with the functional IMPT and as high as 26% in reduction for individual patient when compared to the standard IMPT planning. Functional IMPT was able to spare healthy lung tissue to avoid excess dose to normal structures while maintaining satisfying target coverage. NTCP calculation also shows that the risk of pulmonary complications can be further reduced with functional based IMPT. [ABSTRACT FROM AUTHOR]

Cyclophosphamide (CYL) is a chemotherapeutic medication commonly used in managing various malignancies like breast cancer or leukemia. Though, CYL has been documented to induce lung toxicity. Mechanism of CYL toxicity is through oxidative stress and the release of damage-associated molecular patterns (DAMPs). Sesamol (SES) is a natural antioxidant isolated from Sesamum indicum and its effect against CYL-induced lung toxicity is not studied yet. This study aims to investigate whether SES could prevent any deleterious effects induced by CYL on lung using normal human lung cells, WI-38 cell line, without suppressing its efficacy. Cells were pretreated with SES and/or CYL for 24 h, then cell viability was estimated by MTS and trypan blue assays. The mode of cell death was determined by AO/EB staining. Additionally, caspase-3 level, oxidative stress, and inflammatory markers were evaluated by colorimetric and ELISA techniques. qRT-PCR was performed to evaluate RAGE, NF-κB, and Beclin-1 mRNA-expression. CYL-treated WI-38 cells developed a significantly increased cell death with enhanced oxidative and RAGE/NF-κb/Autophagy signaling, which were all attenuated after pretreatment with SES. Thus, we concluded that SES offered a protective role against CYL-induced lung injury via suppressing oxidative stress and RAGE/NF-κB/Autophagy signaling, which is a natural safe therapeutic option against CYL toxicities. [ABSTRACT FROM AUTHOR]

Background. Numerous studies have investigated the relationship of environmental exposure, epigenetic effects, and human diseases. These linkages may contribute to the potential toxicity mechanisms of environmental chemicals. Here, we investigated the epigenetic pulmonary response of hexanal, a major indoor irritant, following inhalation exposure in F-344 rats. Methods. Based on DNA methylation profiling in gene promoter regions, we identified hexanal-characterized methylated sites and target genes using an unpaired t-test with a fold-change cutoff of - 3.0 and a p-value < 0.05. We also conducted an integrated analysis of DNAmethylation and mRNAexpression data to identify core anti-correlated target genes of hexanal exposure. To further investigate the potential key biological processes and pathways of core DNAmethylated target genes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. Results. Thirty-six dose-dependent methylated genes and anti-correlated target genes of DNA methylation and mRNA in lung tissue of hexanal exposed F-344 rats were identified. These genes were involved in diverse biological processes such as neuroactive ligand-receptor interaction, protein kinase cascade, and intracellular signaling cascade associated with pulmonary toxicity. These results suggest that novel DNA methylation-based epigenetic biomarkers of exposure to hexanal and elucidate the potential pulmonary toxicological mechanisms of action of hexanal. [ABSTRACT FROM AUTHOR]

Human exposure to cellulose nanocrystal (CNC) is possible during the production and/or use of products containing CNC. The objectives of the current study were to determine the lung toxicity of CNC and the underlying molecular mechanisms of the toxicity. Rats were exposed to air or CNC (20 mg/m3, six hours/day, 14 d) by whole-body inhalation and lung toxicity and global gene expression profile were determined. Significant increases in lactate dehydrogenase activity, pro-inflammatory cytokine levels, phagocyte oxidant production, and macrophage and neutrophil counts were detected in the bronchoalveolar lavage cells or fluid from the CNC exposed rats. Mild lung histological changes, such as the accumulation of macrophages and neutrophils, were detected in the CNC exposed rats. Gene expression profiling by next generation sequencing identified 531 genes whose expressions were significantly different in the lungs of the CNC exposed rats, compared with the controls. Bioinformatic analysis of the lung gene expression data identified significant enrichment in several biological functions and canonical pathways including those related to inflammation (cellular movement, immune cell trafficking, inflammatory diseases and response, respiratory disease, complement system, acute phase response, leukocyte extravasation signaling, granulocyte and agranulocyte adhesion and diapedesis, IL-10 signaling, and phagosome formation and maturation) and oxidative stress (NRF2-mediated oxidative stress response, production of nitric oxide and reactive oxygen species in macrophages, and free radical scavenging). Our data demonstrated that inhalation exposure of rats to CNC resulted in lung toxicity mediated mainly through the induction of inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Copyright of Respiratory Case Reports is the property of LookUs Scientific and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Respiratory Case Reports is the property of LookUs Scientific and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To evaluate the protective effect of Zataria multiflora extract, an antioxidative medicinal plant, against cyclophosphamide (CP)-induced oxidative lung damage in mice. Methods: Mice were intraperitoneally pre-treated with various doses of Zataria multiflora extract (50, 100, 200, and 400 mg/kg) once daily for 7 consecutive days. Animals were then injected with a single 200 mg/kg intraperitoneal dose of CP 1 h after the last administration of O. vulgare. Twenty-four hours later, mice were euthanized, the lungs were immediately removed, and biochemical and histological studies were conducted. Results: A single dose of CP markedly altered the levels of several biomarkers associated with oxidative stress in lung homogenates. Pretreatment with Zataria multiflora significantly inhibited the elevation of lipid peroxidation level and the depletion in glutathione content, and superoxide dismutase and catalase activities induced by CP in lung. In addition, Zataria multiflora effectively alleviated CP-induced histopathological abnormality and pulmonary damages in mice lung tissues. Conclusions: The results reveal that Zataria multiflora protects lung tissues from CP-induced toxicity and suggest a role for oxidative stress in the pathogenesis of lung toxicity produced by CP in mice. Because Zataria multiflora has been extensively used as an additive agent and is regarded as safe, it may be used concomitantly as a good supplement for reducing organ toxicity in patients undergoing chemotherapy, besides their consolidated ethnopharmacological uses. [ABSTRACT FROM AUTHOR]

Background: Palbociclib is a specific inhibitor of cyclin-dependent kinases 4 and 6 that is approved for the treatment of advanced or metastatic breast cancer patients. Despite a good toxicity profile in pivotal trials, where asymptomatic neutropenia was the main adverse effect, its wider use in clinical practice may show less prevalent but serious toxicities. Case Presentation: Here, we describe a case of pneumonitis due to palbocicblib. A 57-year-old female with breast cancer with bone metastasis presented dyspnea at rest 3 months after beginning treatment with palbociclib and letrozole. Palbociclib-induced pneumonitis was considered the most probable cause after ruling out all alternatives, and the patient was successfully treated with steroids and showed complete remission. Conclusions: In summary, we present a well-documented case report of pneumonitis related to palbociclib. However, the mechanism of toxicity is still unknown, and there are as yet no reliable biomarkers to predict toxicity with cyclin-dependent kinase 4/6 inhibitors. In this case report, we alert physicians about new drugs that can provoke old toxicities. [ABSTRACT FROM AUTHOR]

Objectives Small molecule tyrosine kinase inhibitors [smTKI, comprising mostly of Janus kinase (JAK) and to a lesser extent, spleen tyrosine kinase (SyK) inhibitors] modulate the cytokine receptor-mediated intracellular signal cascade, and are an effective treatment for autoimmune diseases and malignancies. As smTKI are novel, long-term safety is uncertain. Due to increasing use, characterization of their true adverse event profile is critical. Methods We performed a systematic review and meta-analysis of all published trial data on the pulmonary and serious adverse effects of smTKIs in autoimmune disease. EMBASE, MEDLINE, CENTRAL and Pneumotox databases were searched up to April 2019 for randomized controlled trials, observational studies and post marketing surveillance, comparing any smTKI with placebo or another therapy, or as monotherapy at different doses. Primary outcomes comprised of any respiratory complications including upper and lower respiratory tract infections (URTI, LRTI), influenza, pneumonia, opportunistic respiratory infections, drug-induced interstitial lung disease, pulmonary embolism and lung neoplasm. Results We identified 4667 citations for screening, and selected 319 studies for full text review. Seventy-nine studies were analysed, including 47 randomized controlled trials, 25 observational studies and seven post-marketing surveillance studies, comprising 159 652 participants. There were significantly increased risks of URTI [risk difference (RD) 0.03; 95% CI: 0.01, 0.05; P  = 0.00; 36 studies, 14 724 participants], LRTI (RD 0.01; 95% CI: 0.00, 0.02; P  = 0.02; 24 studies, 12 302 participants), influenza (RD 0.01; 95% CI: 0.00, 0.01; P  = 0.04; 22 studies, 10 684 participants), and pneumonia (RD 0.00; 95% CI: 0.00, 0.01; P  = 0.02; 33 studies, 15 511 participants). No increased risk was found for other respiratory complications, including pulmonary embolism. Conclusion SmTKI increases the risk of non-opportunistic respiratory infections compared with placebo. The risk of any serious pulmonary adverse events is low. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiotherapy (SBRT) is the standard care for inoperable early stage non‐small cell lung cancer (NSCLC). The purpose of our study was to investigate whether a prediction model based on cone‐beam CT (CBCT) plus pretreatment CT radiomics features could improve the prediction of tumor control and lung toxicity after SBRT in comparison to a model based on pretreatment CT radiomics features alone. Methods: A total of 34 cases of stage I NSCLC patients who received SBRT were included in the study. The pretreatment planning CT and serial CBCT radiomics features were analyzed using the imaging biomarker explorer (IBEX) software platform. Multivariate logistic regression was conducted for the association between progression‐free survival (PFS), lung toxicity and features. The predictive capabilities of the models based on CBCT and CT features were compared using receiver operating characteristic (ROC) curves. Results: Five CBCT features and two planning CT features were correlated with disease progression. Six CBCT features and two planning CT features were related to lung injury. The ROC curves indicated that the model based on the CBCT plus planning CT features might be better than the model based on the planning CT features in predicting lung injury. The other ROC curves indicated that the model based on the planning CT features was similar to the model based on the CBCT plus planning CT features in predicting disease progression. Conclusions: Both pretreatment CT and CBCT radiomics features could predict disease progression and lung injury. A model with CBCT plus pretreatment CT radiomics features might improve the prediction of lung toxicity in comparison with a model with pretreatment CT features alone. Key points: Significant findings of the study: A model with cone‐beam CT radiomics features plus pre‐treatment CT radiomics features might improve the prediction of lung toxicity after SBRT in stage I NSCLC patients.What this study adds: In the prediction of PFS and lung toxicity in early‐stage NSCLC patients treated with SBRT, CBCT radiomics could be another effective method. [ABSTRACT FROM AUTHOR]

Lead (Pb) is recognized as the first heavy metal of the top six toxic air pollutants threatening human health and the second hazardous substance. Pb exposure is associated with lung impairment and high incidences of lung cancer. Nuclear factor kappa B (NF-κB) and aryl hydrocarbon receptor (AhR) signaling pathways are known to be expressed and play an important role in the lung. However, the link between Pb lung toxicity and NF-κB and/or AhR pathways remains unclear. This study was established to explore the role of NF-κB and AhR modulation in Pb-induced lung toxicity in human lung cancer A549 cells. In the current study, treatment of A549 cells with Pb significantly induced cell apoptosis as evidenced by increasing a) the percentage of cells underwent apoptosis determined by flow cytometry and b) p53 mRNA level. Pb treatment induced oxidative stress by a) increasing the formation of reactive oxygen species and b) decreasing GSTA1 mRNA levels. The toxic effects of Pb on the lung was associated with significant increases in NF-κB and AhR levels which was accompanied with increases in downstream targets genes, iNOS and CYP1A1, respectively. Inhibition of NF-κB or AhR either chemically using resveratrol or genetically using small interfering RNA (siRNA) significantly rescued A549 cells from Pb-mediated lung toxicity. The results clearly indicate that Pb-mediated lung toxicities are NF-κB and AhR-dependent mechanism. [ABSTRACT FROM AUTHOR]

One-in-five Hodgkin Lymphoma (HL) patients treated with bleomycin develop bleomycin pulmonary toxicity (BPT). Given bleomycin-omission data with negative interim-PET, we assessed changes in BPT statistics. We retrospectively evaluated 126 ABVD-treated HL patients for overall survival (OS), progression-free survival (PFS), BPT factors, and management. Forty-seven patients developed BPT with 17% BPT-mortality. In univariable analysis, OS was negatively impacted by BPT (HR = 3.6, 95%CI = 1.2–10.6), but not bleomycin-omission (HR = 1.3, 95%CI = 0.5–3.7). In multivariable analysis, BPT was not associated with OS (HR = 3.0, 95%CI = 0.9–9.9). BPT patients were older (46 y vs 33 years) and received less bleomycin (107 vs 215 units) compared to non-BPT patients. BPT was managed primarily with bleomycin-omission. "Recent Era" patients had lower BPT rates (28% vs 48%), mortality (10% vs 21%), and bleomycin doses (7 vs 12 doses), yet higher bleomycin-omission in the absence of the BPT (59% vs 8%) compared to "Early Era". Our data suggest BPT continually impacts OS in ABVD-treated HL patients, however management is changing. [ABSTRACT FROM AUTHOR]