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Introduction: Exposure to particulate matter ≤2.5 μm in diameter (PM2.5) is associated with adverse respiratory outcomes, including alterations to lung morphology and function. These associations were reported even at concentrations lower than the current annual limit of PM2.5. Inhalation of PM2.5, of which diesel exhaust particles (DEPs) is a major component, induces lung inflammation and oxidative stress. α-Bisabolol (BIS) is a bioactive dietary phytochemical with various pharmacological properties, including anti-inflammatory and antioxidant actions. Here, we evaluated the possible protective effects of BIS on DEP-induced lung injury. Methods: Mice were exposed to DEPs (20 µg/mouse) or saline (control) by intratracheal instillation. BIS was administered orally at two doses (25 and 50 mg/kg) approximately 1 h before DEP exposure. Twenty-four hours after DEP administration, multiple respiratory endpoints were evaluated. Results: BIS administration was observed to prevent DEP-induced airway hyperreactivity to methacholine; influx of macrophages, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid; and increases in epithelial and endothelial permeabilities. DEP exposure caused increases in the levels of myeloperoxidase, proinflammatory cytokines, and oxidative stress markers in lung tissue homogenates, and all these effects were abated by BIS treatment. The activities of mitochondrial complexes I, II, III, and IV were markedly increased in the lungs of mice exposed to DEPs, and these effects were significantly reduced in the BIS-treated group. Intratracheal instillation of DEPs induced DNA damage and increase in the apoptotic marker cleaved caspase-3. The latter effects were prevented in mice treated with BIS and exposed to DEPs. Moreover, BIS mitigated DEP-induced increase in the expression of phospho-c-Jun N-terminal kinase (JNK) in a dose-dependent manner. Discussion: BIS markedly alleviated DEP-induced lung injury by regulating the inflammatory, oxidative stress, and apoptotic biomarkers through the JNK signaling pathway. Following additional studies, BIS may be considered as a plausible protective agent against inhaled-particle-induced pulmonary adverse effects. [ABSTRACT FROM AUTHOR]

While the pulmonary effects of regular waterpipe smoking (R-WPS) are well-defined, the impact of occasional waterpipe smoking (O-WPS) on the lungs remains less established. This study investigated the pulmonary toxicity and underlying mechanisms of O-WPS versus R-WPS following 6 months of exposure, focusing on histopathology, inflammation in the lung, bronchoalveolar lavage fluid (BALF), and plasma, as well as oxidative stress, genotoxicity, mitochondrial dysfunction, and the expression of mitogen-activated protein kinases (MAPKs) in lung homogenates. Exposure to both O-WPS and R-WPS resulted in significant histological changes, including increased numbers of alveolar macrophages and lymphocytes, as well as interstitial fibrosis. Only R-WPS increased the number of neutrophil polymorphs and plasma cells. R-WPS also significantly increased the chemokines CXCL1, CXCL2, and CCL2 in the lung, BALF, and plasma, while O-WPS increased CXCL1 and CXCL2 in the lung and CXCL1 in the plasma. Both exposure regimens significantly increased lung injury markers, including matrix metalloproteinase-9 and myeloperoxidase. Additionally, R-WPS induced a significant increase in the cytokines IL1β, IL6, and TNFα in the lung, BALF, and plasma, while O-WPS elevated IL1β and IL6 in the lung. Oxidative stress was observed, with increased levels of thiobarbituric acid reactive substances and superoxide dismutase in both the O-WPS and R-WPS groups. Exposure to either O-WPS or R-WPS triggered genotoxicity and altered mitochondrial complex activities. R-WPS exposure also resulted in elevated expression of p-JNK/JNK, p-ERK/ERK, and p-p38/p38, while O-WPS augmented the p-ERK/ERK ratio in the lungs. Taken together, these findings indicate that both O-WPS and R-WPS contribute to lung injury and induce inflammation, oxidative stress, genotoxicity, and mitochondrial dysfunction, with R-WPS having a more pronounced effect. These effects were associated with the activation of MAPKs. [ABSTRACT FROM AUTHOR]

The toxicity of inhaled particulate air pollution perseveres even at lower concentrations than those of the existing air quality limit. Therefore, the identification of safe and effective measures against pollutant particles‐induced vascular toxicity is warranted. Carnosol is a bioactive phenolic diterpene found in rosemary herb, with anti‐inflammatory and antioxidant actions. However, its possible protective effect on the thrombotic and vascular injury induced by diesel exhaust particles (DEP) has not been studied before. We assessed here the potential alleviating effect of carnosol (20 mg/kg) administered intraperitoneally 1 h before intratracheal (i.t.) instillation of DEP (20 μg/mouse). Twenty‐four hours after the administration of DEP, various parameters were assessed. Carnosol administration prevented the increase in the plasma concentrations of C‐reactive protein, fibrinogen, and tissue factor induced by DEP exposure. Carnosol inhibited DEP‐induced prothrombotic effects in pial microvessels in vivo and platelet aggregation in vitro. The shortening of activated partial thromboplastin time and prothrombin time induced by DEP was abated by carnosol administration. Carnosol inhibited the increase in pro‐inflammatory cytokines (interleukin‐6 and tumor necrosis factor α) and adhesion molecules (intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, E‐selectin, and P‐selectin) in aortic tissue. Moreover, it averted the effects of DEP‐induced increase of thiobarbituric acid reactive substances, depletion of antioxidants and DNA damage in the aortic tissue. Likewise, carnosol prevented the decrease in the expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) caused by DEP. We conclude that carnosol alleviates DEP‐induced thrombogenicity and vascular inflammation, oxidative damage, and DNA injury through Nrf2 and HO‐1 activation. [ABSTRACT FROM AUTHOR]

Background/Aims: Inhaled particulate air pollution is associated with cardiotoxicity with underlying mechanisms including oxidative stress and inflammation. Carnosol, commonly found in rosemary and sage, is known to possess a broad range of therapeutic properties such as antioxidant, anti-inflammatory and antiapoptotic. However, its cardioprotective effects on diesel exhaust particles (DEPs)-induced toxicity have not been studied yet. Hence, we evaluated the potential ameliorative effects of carnosol on DEPs-induced heart toxicity in mice, and the underlying mechanisms involved. Methods: Mice were intratracheally instilled with DEPs (1 mg/kg) or saline, and 1 hour prior to instillation they were given intraperitoneally either carnosol (20 mg/kg) or saline. Twenty-four hours after the DEPs instillation, multiple parameters were evaluated in the heart by enzyme-linked immunosorbent assay, colorimetric assay, Comet assay and Western blot technique. Results: Carnosol has significantly reduced the elevation in the plasma levels of lactate hydrogenase and brain natriuretic peptide induced by DEPs. Likewise, the augmented cardiac levels of proinflammatory cytokines, lipid peroxidation, and total nitric oxide in DEPs-treated groups were significantly normalized with the treatment of carnosol. Moreover, carnosol has markedly reduced the heart mitochondrial dysfunction, as well as DNA damage and apoptosis of mice treated with DEPs. Similarly, carnosol significantly reduced the elevated expressions of phosphorylated nuclear factor-кB (NF-кB) and mitogenactivated protein kinases (MAPKs) in the hearts. Furthermore, the treatment with carnosol has restored the decrease in the expression of sirtuin-1 in the hearts of mice exposed to DEPs. Conclusion: Carnosol significantly attenuated DEP-induced cardiotoxicity in mice by suppressing inflammation, oxidative stress, DNA damage, and apoptosis, at least partly via mechanisms involving sirtuin-1 activation and the inhibition of NF-кB and MAPKs activation. [ABSTRACT FROM AUTHOR]

Waterpipe tobacco smoking (WPS) inhalation has been shown to trigger endothelial dysfunction and atherosclerosis. However, the mechanisms underlying these effects are still unknown. Here, we assessed the impact and underlying mechanism of WPS exposure for one month on endothelial dysfunction using aortic tissue of mice. The duration of the session was 30 min/day and 5 days/week. Control mice were exposed to air. Inhalation of WPS induced an increase in the number of macrophages and neutrophils and the concentrations of protein, tumor necrosis factor α (TNF α), interleukin (IL)-1β, and glutathione in bronchoalveolar lavage fluid. Moreover, the concentrations of proinflammatory cytokines (TNF α, IL-6 and IL-1β), adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin and P-selectin) and markers of oxidative stress (lipid peroxidation, glutathione, superoxide dismutase and nitric oxide) in aortic homogenates of mice exposed to WPS were significantly augmented compared with air-exposed mice. Likewise, the concentration of galectin-3 was significantly increased in the aortic homogenates of mice exposed to WPS compared with control group. WPS inhalation induced vascular DNA damage assessed by comet assay and apoptosis characterized by a significant increase in cleaved caspase-3. While the aortic expression of phosphorylated nuclear factor κB (NF-κB) was significantly increased following WPS inhalation, the concentration of sirtuin 1 (SIRT1) was significantly decreased in WPS group compared with air-exposed group. In conclusion, our study provided evidence that WPS inhalation triggers lung injury and endothelial inflammation, oxidative stress and apoptosis which were associated with nuclear factor-κB activation and SIRT1 down-regulation. [ABSTRACT FROM AUTHOR]

Background/Aims: Waterpipe smoke (WPS) is the second most prevalent form of smoking in the world. There are ample evidences about the vascular alterations caused by regular WPS (Reg-WPS). Nonetheless, comparison of the chronic vascular response induced by regular versus occasional WPS (Occ-WPS) exposure is very scarce. Methods: We investigated, in BALB/c mice, the effects of Occ-WPS (30 minutes/day, 1 day/week) versus Reg-WPS (30 minutes/day, 5 days/week) for 6 months on thrombogenicity and platelet aggregation in vivo and in vitro. Moreover, various markers of endothelial integrity, inflammation and oxidative stress were assessed by enzyme-linked immunosorbent assay and colorimetric assay. Control mice were exposed to air. Results: Our results showed that either Occ-WPS or Reg-WPS exposure shortened the thrombotic time in pial microvessels in vivo. Moreover, in pial venules, this effect was more marked in Reg-WPS group (-47%) compared with Occ-WPS (-34%). Similarly, exposure to either Occ-WPS or Reg-WPS reduced the prothrombin time and activated partial thromboplastin time. Platelet count was increased only in Reg-WPS exposure. Exposure to either Occ-WPS or Reg-WPS induced platelet aggregation in vitro. In addition, there was a statistically significant difference between Occ-WPS and Reg-WPS groups in platelet count and aggregation. Plasma concentration of tissue factor (+98%), P-selectin (+14%) and E-selectin (+16%) were significantly increased in Occ-WPS group compared with air exposed group. Likewise, compared with air group Reg-WPS caused an increase in concentration of tissue factor (+193%), P-selectin (+21%) and E-selectin (+42%). Nevertheless, only Reg-WPS induced a decrease (-38%) in the plasma concentration of tissue plasminogen activator. Notably, our results showed a statistically significant difference between Occ-WPS and Reg-WPS groups in the concentration of tissue factor. Erythrocyte numbers, hemoglobin concentration, hematocrit and lactate dehydrogenase activity were augmented only in Reg-WPS group compared with either control or Occ-WPS groups. Likewise, only Reg-WPS induced an increase in proinflammatory cytokines, tumor necrosis factor-α and interleukin1β compared with either control or Occ-WPS groups. However, markers of oxidative stress including 8-isoprostane and total antioxidants were enhanced in both Occ-WPS and RegWPS compared with control group. Conclusion: Our data confirm the vascular toxicity of the chronic Reg-WPS exposure and shows that even occasional chronic exposure to WPS caused thrombosis, platelet aggregation, endothelial alterations and oxidative stress. The latter findings are an additional cause of concern about the long-term toxicity of occasional waterpipe smoking. [ABSTRACT FROM AUTHOR]

Hypertension is a risk factor for vascular injury and thrombotic complications, and smoking tobacco is a risk factor for the development and exacerbation of hypertension. The influence of waterpipe smoke (WPS) on coagulation and vascular injury in hypertension is not fully understood. Here, we evaluated the effects of WPS in mice made hypertensive (HT) by infusing angiotensin II (Ang II) for 42 days. On day 14 of the infusion of Ang II or vehicle (normotensive; NT), mice were exposed either to air or WPS for four consecutive weeks. Each session was 30 min/day for 5 days/week. The concentrations of tissue factor, von Willebrand factor, fibrinogen, and plasminogen activator inhibitor-1 were elevated in the HT + WPS group versus either HT + air or NT + WPS groups. Similarly, in the HT + WPS group, thrombogenicity was increased both in vivo and in vitro, compared with either HT + air or NT + WPS groups. In aortic tissue, adhesion molecules including P-selectin, E-selectin, intercellular adhesion molecule-1, and vascular adhesion molecule-1 were increased in the HT + WPS group versus the controls. Likewise, various proinflammatory cytokines and markers of oxidative stress augmented in the HT + WPS group compared with either HT + air or NT + WPS. DNA damage, cleaved caspase-3, and cytochrome C were increased in the HT + WPS group versus the controls. The immunohistochemical expression of nuclear factor erythroid 2-related factor 2 was increased in the HT + WPS group versus either HT + air or NT + WPS. Taken together, our findings show that WPS exposure intensified thrombogenicity and vascular damage in experimentally induced hypertension. Our data suggest that vascular toxicity of WPS may be exaggerated in hypertensive patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2025 Sumaya Beegam et al. Oxidative Medicine and Cellular Longevity published by John Wiley & Sons Ltd.)