Mechanisms Of Lung Toxicity Research Articles

Understanding fenpropathrin-induced pulmonary toxicity: What apoptosis, inflammation, and pyreptosis reveal analyzing cross-links at the molecular, immunohistochemical, and immunofluorescent levels

Fenpropathrin (FN), a pyrethroid has been linked to potential pulmonary toxic effects to humans via incident direct or indirect ingestion. Thus, we aimed to the investigate the underlying mechanisms of lung toxicity upon exposure to FN in the rat model, besides studying whether curcumin (CCM) and curcumin-loaded chitosan nanoformulation (CCM-Chs) can mitigate FN-induced lung damage. Six distinct groups, namely, control, CCM, CCM-Chs, FN, and CCM + FN, CCM-Chs + FN were assigned separately. The inflammatory, apoptotic, and oxidative stress states, histological, immunohistochemical, and immunofluorescence examination of different markers within the pulmonary tissue were applied. The results revealed that the FN-induced tissue damage might be caused by the oxidative stress induction and depressed antioxidant glutathione system in the lungs of rats. Furthermore, FN upregulated the expression of genes related to inflammation, and pyroptosis, and elevated the immunoreactivity of Caspase-3, tumor necrosis factor-α, vimentin, and 4-Hydroxynonenal in pulmonary tissues of FN-exposed rats compared to the control. CCM and CCM-Chs mitigated the FN-induced disturbances, while remarkably, CCM-Chs showed better potency than CCM in mitigating the FN-induced toxicity. In conclusion, this study shows the prominent preventive ability of CCM-Chs more than CCM in combatting the pulmonary toxicity induced by FN. This may be beneficial in developing therapeutic and preventive strategies against FN-induced pulmonary toxicity.

Mechanistic study of C5F10O-induced lung toxicity in rats: An eco-friendly insulating gas alternative to SF6

The global warming and other environmental problems caused by SF6 emissions can be reduced due to the widespread use of eco-friendly insulating gas, perfluoropentanone (C5F10O). However, there is an exposure risk to populations in areas near C5F10O equipment, so it is important to clarify its biosafety and pathogenesis before large-scale application. In this paper, histopathology, transcriptomics, 4D-DIA proteomics, and LC-MS metabolomics of rats exposed to 2000 ppm and 6000 ppm C5F10O are analyzed to reveal the mechanisms of toxicity and health risks. Histopathological shows that inflammatory cell infiltration, epithelial cell hyperplasia, and alveolar atrophy accompanied by alveolar wall thickening are present in both low-dose and high-dose groups. Analysis of transcriptomic and 4D-DIA proteomic show that Cell cycle and DNA replication can be activated by both 2000 ppm and 6000 ppm C5F10O to induce cell proliferation. In addition, it also leads to the activation of pathways such as Antigen processing and presentation, Cell adhesion molecules and Complement and coagulation cascades, T cell receptor signal path, Th1 and T cell receptor signal path, Th1 and Th2 cell differentiation, complement and coagulation cascades. Finally, LC-MS metabolomics analysis confirms that the metabolic pathways associated with glycerophospholipids, arachidonic acid, and linoleic acid are disrupted and become more severe with increasing doses. The mechanism of lung toxicity caused by C5F10O is systematically expounded based on the multi-omics analysis and provided biosafety references for further promotion and application of C5F10O.

TRAF2/ASK1/JNK Signaling Pathway Is Involved in the Lung Apoptosis of Swine Induced by Cadmium Exposure.

Cadmium (Cd), a toxic heavy metal, exists widely in the environment, which can enter organisms through a variety of ways and cause damage to various organs and tissues. However, the mechanism of lung toxicity in swine after Cd exposure is still unclear. To explore the molecular mechanism of swine lung damage caused by Cd exposure, we established the model of Cd exposure, and Cd chloride (20mg/kg CdCl2) was added to the diet of swine for continuous exposure for 40days. TUNEL staining showed that the apoptosis of swine lung increased significantly after Cd exposure. Meanwhile, the results of qRT-PCR showed that Cd induced oxidative stress and inhibited the expression of antioxidant enzymes including CAT, GCLM, GST, SOD, and GSH-px in lung tissue. Cd exposure activated mitochondrial apoptosis pathway via the TRAF2/ASK1/JNK signaling pathway. In brief, we considered that Cd exposure causes oxidative stress in lung and induces lung cell apoptosis through the TRAF2/ASK1/JNK pathway and increases the expression of HSPs to resist the toxicity of Cd. Our research enriches the theoretical basis of Cd toxicity and provides reference for comparative medicine.

Paraquat Poisonings: Mechanisms of Lung Toxicity, Clinical Features, and Treatment

Paraquat dichloride (methyl viologen; PQ) is an effective and widely used herbicide that has a proven safety record when appropriately applied to eliminate weeds. However, over the last decades, there have been numerous fatalities, mainly caused by accidental or voluntary ingestion. PQ poisoning is an extremely frustrating condition to manage clinically, due to the elevated morbidity and mortality observed so far and due to the lack of effective treatments to be used in humans. PQ mainly accumulates in the lung (pulmonary concentrations can be 6 to 10 times higher than those in the plasma), where it is retained even when blood levels start to decrease. The pulmonary effects can be explained by the participation of the polyamine transport system abundantly expressed in the membrane of alveolar cells type I, II, and Clara cells. Further downstream at the toxicodynamic level, the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. With this review we aimed to collect and describe the most pertinent and significant findings published in established scientific publications since the discovery of PQ, focusing on the most recent developments related to PQ lung toxicity and their relevance to the treatment of human poisonings. Considerable space is also dedicated to techniques for prognosis prediction, since these could allow development of rigorous clinical protocols that may produce comparable data for the evaluation of proposed therapies.

Characterization of the biochemical effects of 1-nitronaphthalene in rats using global metabolic profiling by NMR spectroscopy and pattern recognition

Metabolic fingerprints, in the form of patterns of high-concentration endogenous metabolites, of 1-nitronaphthalene (NN)-induced lung toxicity have been elucidated in bronchoalveolar lavage fluid (BALF), urine, blood plasma, and intact lung and liver tissue using NMR spectroscopy-based metabolic profiling. A single dose of NN (75 mg kg−1) was administered orally to Sprague–Dawley rats. BALF and lung tissue were obtained 24 h after dosing from these animals and matched control rats post-mortem. High-resolution 1H-NMR spectroscopy of BALF samples indicated that NN caused increases in concentrations of choline, amino acids (leucine, isoleucine and alanine) and lactate together with decreased concentrations of succinate, citrate, creatine, creatinine and glucose. In addition, the intact lung weights were higher in the NN-treated group (p<0.01), consistent with pulmonary oedema. The NMR-detected perturbations indicated that NN induces a perturbation in energy metabolism in both lung and liver tissue, as well as surfactant production and osmolyte levels in the lungs. As well as reporting the first NMR spectroscopic combined examination of BALF and intact lung, this study indicates that such holistic approaches to investigating mechanisms of lung toxicity may be of value in evaluating disease progression or the effects of therapeutic intervention in pulmonary conditions such as surfactant disorders or asthma.

Pathology and Mechanism of Lung Toxicity Following Inhalation of Hair Spray in Rats

In order to elucidate the pathology and mechanism of lung toxicity induced by chronic hairspray inhalation, male Wister rats 9 wk of age were exposed to a uniform concentration ofhair spray for up to 12 wk using a jet nebulizer. The aerosol concentration to which the ratswere exposed was about 7 g/m3. Differential cell counts in bronchoalveolar lavage fluid (BALF),the expression of several cytokines from alveolar macrophage using the reverse-transcriptionpolymerase chain reaction (RT-PCR) method, and histopathologic evaluation using a computeraidedgraphic analyzer (IBAS) were conducted 1, 4, 8, and 12wkafter exposure.Over the passageof time, neutrophils and macrophages increased in BALF, and neutrophils infiltrated in the lunginterstitium from the peribronchial interstitium to the alveolar septum. Alveolar macrophagesshowed increased expression of both the mRNA of tumor necrosis factor (TNF)-α and themRNA of the chemokines macrophage inflammatory protein 2 (MIP2) and cytokine-inducedneutrophil attractant (CINC). Fromthese findings, chronic inhalation of hair spray is consideredto induce at first intra-alveolar accumulation and activation of alveolar macrophages, followedby recruitment of neutrophils in the lung through the expression of proinflammatory cytokine,CINC, and MIP2, which cause predominantly neutrophilic inflammation in the lung.