IntroductionExposure to waterpipe smoke (WPS) in humans and experimental animals has been reported to cause oxidative stress and thrombotic complications. L-2-Oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug that maintains glutathione (GSH) in tissues. Nevertheless, the possible mitigating effects of OTC on platelet aggregation induced by WPS inhalation, and its underlying mechanisms of action remain unexplored. This is the goal of the present work in BALB/c mice. Methods Animals were exposed to either WPS or air (control) by inhalation daily for 30 min for 1 month. OTC was given 1 h before each exposure session by gavage at a dose of 80 mg/kg. Results WPS inhalation increased various markers of platelet aggregation, coagulation, fibrinolysis and endothelial integrity (platelet factor 4, tissue factor, fibrinogen, thrombin-antithrombin complexes, plasminogen activator inhibitor, P-selectin, E-selectin, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1). It also shortened the prothrombin time and partial thromboplastin time and augmented the plasma concentrations of C-reactive protein and triglycerides. All these effects were attenuated by OTC treatment. Likewise, OTC administration significantly mitigated platelet aggregation in vivo. Platelets isolated from mice exposed to WPS showed high levels of markers of oxidative and nitrosative stress, calcium, annexin V and calpain. The latter effects were significantly alleviated by OTC treatment. Discussion Our data show that OTC administration significantly mitigated WPS-induced in vivo endothelial injury and thrombotic events, as well as platelet oxidative stress and apoptosis. This finding provides evidence on the mechanisms of toxicity of WPS on platelet physiology, and the alleviative action of OTC.

Regular hookah smoking (Reg-HS) has become a major global public health issue, linked to significant health risks, including kidney damage. A less frequent pattern of use, known as occasional hookah smoking (Occ-HS), is also common; however, there has been little progress in understanding the direct impact of Occ-HS on kidneys. To investigate how varying frequencies of HS inhalation affect the kidney, we exposed mice to nose-only HS under two regimens, occasional (30 min once weekly) and regular (30 min five times per week) for a duration of 6 months. This study explored the impact on renal damage, inflammatory responses, oxidative stress levels, genotoxicity, and mitochondrial activity as well as the possible modulation of MAPK signaling pathway. Both Occ-HS and Reg-HS led to a marked elevations in plasma levels of urea and creatinine (p < 0.05-p < 0.0001). Additionally, concentrations of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were significantly increased in both groups (p < 0.01-p < 0.0001). Notably, only the Reg-HS regimen induced a substantial rise in plasma levels of indoxyl sulfate, cystatin C, and adiponectin (p < 0.01-p < 0.0001). Similarly, relative to the control group, mice subjected to Reg-HS exposure exhibited significantly elevated levels of proinflammatory cytokines, tumor necrosis factor-α, and interleukin-6 (p < 0.0001). Exposure to either Occ-HS or Reg-HS caused significant increase in interleukin-1β (p < 0.05, p < 0.0001), thiobarbituric acid reactive substances (TBARS; p < 0.05, p < 0.0001) compared with air-exposed mice. Our findings revealed that Occ-HS inhalation triggered only a decrease in superoxide dismutase (SOD) activity (p < 0.001). On the other hand, nitric oxide (NO; p < 0.001), SOD (p < 0.0001), and Glutathione (GSH; p < 0.0001) levels were significantly decreased in Reg-HS group. Furthermore, DNA damage marker, 8-Hydroxy-2'-deoxyguanosine was significantly augmented in both regimens (p < 0.0001). Exposure to both regimens resulted in significant elevation in mitochondrial complexes I, II and III, and IV (p < 0.0001). Increased expression of activation of mitogen-activated protein kinases (MAPKs) was observed exclusively in the Reg-HS group, as evidenced by increased levels of p-JNK, p-p38, and p-ERK (p < 0.001-p < 0.0001). In conclusion, our study is the first to demonstrate that despite the significant differences in the amount of smoke inhaled, both Occ-HS or Reg-HS inhalation deteriorate kidney function and induce oxidative damage, inflammatory response, DNA injury, and mitochondrial impairment with modulation of the MAPK signaling. These findings highlight the importance of further research into the public health risks associated with occasional hookah smoking.

Hookah smoke (HS) inhalation is known to induce cardiovascular dysfunction, including oxidative stress and inflammation. The procysteine, 2-oxo-(4R)-4-thiazolidinecarboxylic acid (OTC) is a prodrug of cysteine, a precursor of glutathione, which is a major intracellular antioxidant. This study aimed to evaluate the possible cardioprotective effects of OTC against HS inhalation-induced cardiac injury in mice. The animals were exposed to HS for 30 min per day, five days per week, for one month, while control mice were exposed to normal air. OTC was administered by gavage at a dose of 80 mg/kg 1 h before each exposure session. OTC prevented HS-induced increase in the concentrations of tumor necrosis factor α, interleukin (IL)-6 and galectin-3 in the heart tissue. HS exposure augmented the levels of markers of oxidative stress and adhesion molecules. The latter effects were significantly abrogated by OTC treatment. Likewise, the cardiac DNA damage and apoptosis triggered by HS inhalation were significantly prevented in mice treated with OTC. The concentrations of NLRP3 inflammasome and IL-1β in the hearts of mice exposed to HS were significantly augmented, and OTC treatment significantly abated this effect. Moreover, while the cardiac expression of phosphorylated nuclear factor κB (NF-κB) was increased, that of sirtuin-1 was significantly decreased by HS inhalation. Both effects were significantly mitigated by OTC administration. Furthermore, HS inhalation induced an elevation in the concentrations of mammalian targets of rapamycin and nuclear factor erythroid-derived 2-like 2 (Nrf2) expression in the heart, and this effect was significantly potentiated in the OTC + HS group. Despite these molecular and biochemical alterations, no detectable differences in cardiac histology were observed among the experimental groups. Collectively, these findings demonstrate that OTC mitigates HS-induced cardiac injury by reducing oxidative stress, inflammation, DNA damage, and apoptosis through mechanisms that involve inhibition of NLRP3 inflammasome activation and NF-κB signaling, together with activation of sirtuin-1 and Nrf2 pathways.

Background:Risk assessments usually test active ingredients but not full commercial formulations. We compared cytotoxic and genotoxic effects of three glyphosate-based herbicides (Roundup Mega, Glyfos, Fozat-480) and two co-formulants (ROKAmin SR22, EMPIGEN BB) in human HL60 (leukocyte) and HepG2 (hepatocyte) cells. Methods:Cells were exposed for 1 h to increasing concentrations (0.1-10,000 μM depending on formulation). Cytotoxicity was measured by propidium iodide staining; genotoxicity was assessed by the alkaline comet assay (tail DNA %, tail length, tail moment, Olive tail moment). Positive (100 μM H2O2) and negative controls were included. Data are means of three independent experiments. Results:Cytotoxicity occurred at lower concentrations in HL60 than HepG2. Roundup Mega and Glyfos produced the strongest genotoxic responses; Roundup Mega increased tail length in HL60 from 0.1 μM, while Glyfos produced consistent genotoxicity in HepG2 from 100 μM. Co-formulants alone showed limited genotoxicity, though ROKAmin SR22 induced DNA% in tail at higher concentrations. Genotoxic effects often occurred at sub-cytotoxic concentrations. Conclusion:Commercial GBH formulations can be more genotoxic than the active ingredient alone; formulation composition influences potency and target-cell sensitivity. These results support formulation-specific testing to improve human health risk assessment.

Introduction:Copper oxide nanoparticles (CuONPs) are increasingly used in industrial and biomedical applications; however, their potential to provoke systemic vascular and hemostatic disturbances remains poorly defined. Methods:BALB/c mice were subjected to a single pulmonary instillation of CuONPs at doses of 3 µg or 30 µg per mouse, and the endpoints were evaluated 24 h post-exposure. Prior to biological testing, the CuONPs were characterized by X-ray diffraction, dynamic light scattering, zeta potential analyses and transmission electron microscopy, confirming their high crystallinity, relatively uniform particle size distribution and good electrostatic stability. Results:Exposure to CuONPs significantly shortened the thrombotic occlusion times in arterioles and venules; reduced prothrombin and activated partial thromboplastin times; and elevated plasma platelet factor 4, fibrinogen, plasminogen activator inhibitor-1, and C-reactive protein levels, indicating a shift toward a prothrombotic state. Oxidative stress is evidenced by increased levels of thiobarbituric acid-reactive substances, depleted glutathione levels, and decreased nitric oxide levels. In parallel, CuONPs induced significant upregulation of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1β) and markers of DNA damage and apoptosis, including 8-hydroxy-2'-deoxyguanosine, cytochrome C release, and cleaved caspase-3 expression. Discussion:Collectively, these findings demonstrated that pulmonary exposure to low and high doses of CuONPs triggered systemic oxidative stress and inflammation, leading to prothrombotic responses, DNA damage, and apoptosis. This study highlights the potential vascular risks associated with CuONPs and underscores the importance of careful safety evaluation in biomedical and environmental contexts.

Ceramides (Cer) drive cardiometabolic disease (CMD) by promoting lipotoxicity and oxidative stress, yet their therapeutic potential remains underexplored. We investigated Cer dysregulation in high-fat diet (HFD) fed rats and evaluated three antidiabetic drugs (Sitagliptin, Liraglutide, Saxagliptin) for Cer-modulating effects. HFD elevated CerC16:0 and CerC18:0 across different tissues (serum, heart and liver), with pronounced cardiac CerC18:0 accumulation (1.37 ± 0.103 nmol/g, p < 0.001). Cer changes preceded alterations in traditional metabolic markers (glucose, cholesterol and triglycerides), suggesting early biomarker potential. In a five weeks pilot study (n = 24), Sitagliptin (Sita) outperformed Liraglutide and Saxagliptin in reducing Cer levels. Extended experiments (n = 48) showed Sita significantly decreased harmful Cer ratios (CerC16:0/24:0, CerC18:0/24:0), reduced oxidative stress and tissue lipid accumulation, while enhancing urinary CerC16:0 excretion index (p < 0.01). Sita restored cardioprotective signaling (eNOS, pAKT, cTnT) and mitigated apoptosis and steatosis. These findings highlight Cer as early indicators of lipotoxic injury and support Sita’s potential for CMD therapy through modulation of Cer metabolism, warranting further clinical exploration.

Background Diabetes mellitus (DM), a metabolic disorder that leads to chronic hyperglycemia, is one of the topmost global public health concerns according to the International Diabetes Federation. Adropin is a peptide hormone that is primarily involved in energy homeostasis, but its involvement in other biological activities such as lowering hyperlipidemia, and diminishing insulin resistance has also been reported. In this study, we aimed to explore additional effects of adropin on oxidative stress, inflammation, and cell proliferation in an animal model of type 1 DM. Methods To achieve our aim, normal and diabetic Wistar rats were treated with adropin (2.1 μg/kg/day) for a period of 10 days. Pancreatic tissue samples were collected for histomorphological analysis and inflammation assay, while blood was collected for oxidative stress assay. Results Our results showed that diabetes induction stimulated cell proliferation in both exocrine and endocrine pancreas, and adropin dramatically attenuated this effect in pancreatic exocrine tissue, but not in the islet of Langerhans. In addition, adropin significantly increased glutathione reductase expression in pancreatic tissue, and augmented serum total glutathione in the diabetic rats compared to diabetic untreated rats. Conclusion Our study indicates the potential role of adropin in alleviating oxidative stress in DM.

Human exposure to microplastics (MPs) occurs primarily through ingestion, as they contaminate food and water sources and have been detected in biological samples, including urine. Polystyrene MPs (PSMPs), typically ranging from 80 nm to 2 μm, have been shown to cause renal histological changes including tubular injury; however, their impact on chronic kidney disease (CKD) remains unclear. This study examined the effects of PSMPs on a murine model of adenine-induced CKD. Mice were fed either a normal diet or one containing 0.2 % adenine for 7 days followed by 0.15 % adenine for 4 weeks, and exposed to 2 μm PSMPs (0.2 or 0.4 mg/day, twice weekly) for 4 weeks. In healthy mice, PSMPs reduced creatinine clearance and increased plasma urea, creatinine, and urinary albumin/creatinine ratio. In CKD mice, PSMPs further exacerbated renal dysfunction and enhanced histological evidence of tubular injury, inflammation, and interstitial fibrosis. PSMPs exposure increased renal markers of inflammation, oxidative stress, DNA damage, and apoptosis, particularly in the adenine-induced CKD + PSMP group. Likewise, molecular analyses revealed significant activation of nuclear factor kappa B (NF-κB) and selective stimulation of mitogen-activated protein kinase (MAPK) pathways, specifically ERK and p38, while JNK remained unaffected. These molecular changes were accompanied by a pronounced reduction in sirtuin-1 expression. Collectively, the results indicate that PSMPs exposure exacerbates renal injury in CKD by promoting inflammation, oxidative stress, and fibrosis, in association with activation of NF-κB and ERK/p38 signaling and suppression of sirtuin-1. These findings highlight the potential health risks of microplastic exposure in individuals with kidney disease.

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.

Background/Objectives: Inhalation of environmental particulate air pollution has been reported to cause pulmonary and systemic events including coagulation disturbances, systemic inflammation, and oxidative stress. Nerolidol, a naturally occurring sesquiterpene alcohol, has effective antioxidant and anti-inflammatory effects. Hence, the aim in the present investigation was to evaluate the potential ameliorative effects of nerolidol on the coagulation and systemic actions induced by pulmonary exposure to diesel exhaust particles (DEPs). Methods: Nerolidol (100 mg/kg) was given to mice by oral gavage one hour before the intratracheal instillation of DEPs (0.5 mg/kg), and 24 h later various markers of coagulation and systemic toxicity were evaluated. Results: Nerolidol treatment significantly abrogated DEP-induced platelet aggregation in vivo and in vitro. Nerolidol has also prevented the shortening of the prothrombin time and activated plasma thromboplastin time triggered by DEP exposure. Likewise, while the concentrations of fibrinogen and plasminogen activator inhibitor-1 were increased by DEP administration, that of tissue plasminogen activator was significantly decreased. These effects were abolished in the group of mice concomitantly treated with nerolidol and DEP. Moreover, plasma markers of inflammation, oxidative stress, and endothelial dysfunction which were significantly increased in the DEP-treated group, returned to control levels in the nerolidol + DEP group. Nerolidol treatment significantly ameliorated the increase in the concentrations of hypoxia-inducible factor 1α, galectin-3, and neutrophil gelatinase-associated lipocalin induced by pulmonary exposure to DEP. The co-administration of nerolidol + DEPs significantly mitigated the increase in markers of oxidative DNA damage, 8-hydroxy-2-deoxyguanosine, and apoptosis, cleaved-caspase-3, induced by DEP. Conclusions: Collectively, our data demonstrate that nerolidol exert significant ameliorative actions against DEP-induced thrombotic events, endothelial dysfunction, systemic inflammation, oxidative stress, DNA damage, and apoptosis. Pending further pharmacological and toxicological studies, nerolidol could be a promising agent to alleviate the toxicity of inhaled DEPs and other pollutant particles.

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.

IntroductionExposure 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.MethodsMice 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.ResultsBIS 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.DiscussionBIS 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.

Introduction:Cisplatin (CP)-induced acute kidney injury (AKI) is a significant side effect of CP chemotherapy, driven by oxidative stress and inflammation. Sanguinarine (SANG), an alkaloid from the rhizomes of Sanguinaria canadensis and poppy-fumaria species, exhibits antioxidant and anti-inflammatory properties. This study examined SANG's effect on CP-induced AKI in mice and its underlying mechanisms. Methods:Mice were orally administered 5 mg/kg SANG for 10 days. On the seventh day, they received a single intraperitoneal CP injection (20 mg/kg) and were sacrificed on the 11th day. Results:SANG significantly improved CP-induced decreases in body weight, water intake, urine volume, relative kidney weight, creatinine clearance, albumin-to-creatinine ratio, and plasma urea and creatinine levels. It also reduced elevated plasma neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C, and adiponectin levels, as well as renal markers of inflammation and oxidative stress induced by CP administration. SANG normalized kidney mitochondrial dysfunction, DNA damage, and apoptosis caused by CP. It also inhibited the CP-induced increase in the expression of phosphorylated nuclear factor-κB and autophagy markers in the kidney. Histological analysis showed that SANG reduced acute tubular necrosis and intraluminal protein accumulation due to CP. Discussion:In conclusion, SANG mitigated CP-induced AKI by reducing inflammation, oxidative stress, DNA damage, apoptosis, and autophagy. Pending more comprehensive pharmacological and toxicological assessments, SANG may be regarded as a potential therapeutic agent for mitigating CP-induced AKI.

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 mitogen-activated 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.

Aims: The global prevalence of waterpipe tobacco smoking is increasing. Although the cardiorespiratory, renal, and reproductive effects of waterpipe smoking (WPS) are well-documented, there is limited knowledge regarding its adverse impact on the liver. Therefore, our study aimed to assess the effects and potential mechanisms of WPS inhalation for one or four weeks on the liver. Main methods: Mice were exposed to WPS for 30 min per day, five days per week, while control mice were exposed to clean air. Key findings: Analysis using light microscopy revealed the infiltration of immune cells (neutrophils and lymphocytes) accompanied by vacuolar hepatic degeneration upon WPS inhalation. At the four-week timepoint, electron microscopy analysis demonstrated an increased number of mitochondria with a concomitant pinchingoff of hepatocyte plasma membranes. WPS exposure led to a significant rise in the activities of liver enzymes alanine aminotransferase and aspartate aminotransferase in the bloodstream. Additionally, WPS inhalation elevated lipid peroxidation and reactive oxygen species levels and disrupted the levels of the antioxidant glutathione in liver tissue homogenates. The concentration of proinflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)-6, and IL-1 beta, was significantly increased in the WPS-exposed group. Furthermore, WPS inhalation induced DNA damage and a significant increase in the levels of cleaved caspase-3, cytochrome C and hypoxia-inducible factor 1 alpha along with alterations in the activity of mitochondrial complexes I, II, III and IV. Significance: Our findings provide evidence that WPS inhalation triggers changes in liver morphology, oxidative stress, inflammation, DNA damage, apoptosis, and alterations in mitochondrial activity.

Background: Cardiovascular diseases are the leading cause of death worldwide, including the United Arab Emirates. Ischemia–reperfusion (IR) injury results in the death of cardiac myocytes that were viable immediately before myocardial reperfusion. We aim to investigate the role of galectin-3 (Gal-3) in autophagy during ischemia–reperfusion injuries. Methods: Male C57B6/J and Gal-3 knockout (KO) mice were used for the murine model of IR injury. Heart samples and serum were collected 24 h post-IR and were processed for immunohistochemical and immunofluorescent labeling and an enzyme-linked immunosorbent assay. Results: There was a significant increase in left ventricle (LV) concentrations of Gal-3 in Gal-3 wild-type mice compared to sham mice. There were significantly higher concentrations of LV autophagy proteins and phospho-AMPK in IR Gal-3 KO mice than in IR Gal-3 wild-type mice, compared to lower concentrations of LV phospho-mTOR and p62 in IR Gal-3 KO than in IR wild-type mice. Antioxidant activities were higher in the LVs of IR Gal-3 wild-type mice, while oxidative stress was higher in the LVs of IR Gal-3 KO mice. Conclusions: Our study supports the interaction of Gal-3 with autophagy proteins, oxidative stress, and antioxidant proteins and demonstrates that the absence of Gal-3 can enhance autophagy in the heart after IR injury.

Regular waterpipe smoking (Reg-WPS) is well recognized for its deleterious effect on the heart. However, there is a paucity of experimental studies on the impact of occasional waterpipe smoking (Occ-WPS), also known as nondaily smoking, versus Reg-WPS on cardiac homeostasis, and the mechanisms underlying these effects. Hence, we aimed, in the present study, to investigate the effect of Occ-WPS (30 min/day, 1 day/week) versus Reg-WPS (30 min/day, 5 days/week) for 6 months on systolic blood pressure (SBP), cardiac injury, oxidative markers, chemokines, proinflammatory cytokines, DNA damage and mitochondrial function compared with air (control) exposed mice. Our results show that SBP was increased following exposure to either Occ-WPS or Reg-WPS compared with air-exposed mice. Moreover, we found that only Reg-WPS induced a significant elevation in the levels of troponin I, brain natriuretic peptide, lactate dehydrogenase, and creatine phosphokinase. However, the atrial natriuretic peptide (ANP) was significantly increased in both Occ-WPS and Reg-WPS groups. Compared with air-exposed mice, the levels of lipid peroxidation, reduced glutathione and monocyte chemoattractant protein-1 were only significantly augmented in the Reg-WPS. However, catalase, superoxide dismutase, and CXCL1 were significantly increased in both Occ-WPS and Reg-WPS. The concentrations of the adhesion molecules E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 were solely elevated in the heart of mice exposed to Reg-WPS. Similarly, the concentrations of interleukin-1β and tumor necrosis factor α were only significantly augmented in the Reg-WPS. However, both Occ-WPS and Reg-WPS triggered significant augmentation in the levels of IL17 and DNA damage compared to the control groups. Furthermore, while Occ-WPS induced a slight but statistically insignificant elevation in the concentrations of mammalian targets of rapamycin and nuclear factor erythroid-derived 2-like 2 (Nrf2) expression, Reg-WPS exposure increased their levels substantially, in addition to p53 and mitochondrial complexes II & III, and IV activities compared with air-exposed mice. In conclusion, our findings show that while the long-term Occ-WPS exposure induced an elevation of SBP, ANP, antioxidant enzymes, IL17, CXCL1, and cardiac DNA damage, Reg-WPS exposure was consistently associated with the elevation of SBP and occurrence of cardiac damage, inflammation, oxidative stress, DNA damage and mitochondrial dysfunction.

Abstract Introduction Exposure to pesticides in Arab countries poses a significant public health concern, given the extensive agricultural activity and pesticide utilization. Methods This systematic review and meta-analysis study aims to assess the genotoxic effects of agricultural pesticide exposure on adult agricultural workers in 19 Middle Eastern countries, identify research gaps, and evaluate methodological constraints. The study protocol, registered as CRD42022314453, conducted a comprehensive database search in PubMed, Scopus, Web of Science, Embase, and Agricola without language restrictions, adhering to PRISMA 2020 guidelines and a structured PECO statement for study selection. Results This search identified just five relevant studies within Egypt, Syria, and Jordan. We assessed the Risk of Bias using a comprehensive tool that aligns with WHO/ILO Joint Estimates and incorporates principles from the Navigation Guide RoB tool and RoB-SPEO domains. Furthermore, we conducted a quantitative meta-analysis on homogeneous data. The results of various genotoxicity assays consistently demonstrate a heightened level of DNA damage in individuals exposed to pesticides compared to their non-exposed counterparts. Notably, farmers exposed to pesticides exhibit a significantly increased occurrence of chromosomal translocation (t(14;18)), micronuclei formation, and chromosomal aberrations. It is noteworthy, however, that only two of these studies assessed cytotoxicity indirectly. Discussion In addition, the limited availability of detailed exposure data necessitates a cautious interpretation of the findings. This review underscores the imperative for further research on the genotoxicity of occupational pesticide exposure in the Middle East. Conclusion By deepening our understanding of the genotoxic effects of pesticide exposure, we can develop more effective strategies to safeguard the health of agricultural workers in Arab countries.

Tobacco smoking is an independent risk factor in the onset of kidney disease. To date, there have been no reports on the influence of waterpipe smoke (WPS) in experimentally induced chronic kidney disease (CKD) models. We studied the effects and mechanisms of actions of WPS on a mouse model of adenine-induced CKD. Mice fed either a normal diet, or an adenine-added diet and were exposed to either air or WPS (30 min/day and 5 days/week) for four consecutive weeks. Plasma creatinine, urea and indoxyl sulfate increased and creatinine clearance decreased in adenine + WPS versus either WPS or adenine + saline groups. The urinary concentrations of kidney injury molecule-1 and adiponectin and the activities of neutrophil gelatinase-associated lipocalin and N-acetyl-β-D-glucosaminidase were augmented in adenine + WPS compared with either adenine + air or WPS groups. In the kidney tissue, several markers of oxidative stress and inflammation were higher in adenine + WPS than in either adenine + air or WPS groups. Compared with the controls, WPS inhalation in mice with CKD increased DNA damage, and urinary concentration of 8-hydroxy-2-deoxyguanosine. Furthermore, the expressions of nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) (ERK and p38) were elevated in the kidneys of adenine + WPS group, compared with the controls. Likewise, the kidneys of adenine + WPS group revealed more marked histological tubular injury, chronic inflammation and interstitial fibrosis. In conclusion, WPS inhalation aggravates kidney injury, oxidative stress, inflammation, DNA damage and fibrosis in mice with adenine-induced CKD, indicating that WPS exposure intensifies CKD. These effects were associated with a mechanism involving NF-κB, ERK and p38 activations.

The prevalence of waterpipe tobacco smoking (WPS) is increasing worldwide and is relatively high among youth and young adults. It has been shown, both experimentally and clinically, that WPS exposure adversely affects the cardiovascular and hematological systems through the generation of oxidative stress and inflammation. Our study aimed to evaluate the impact of WPS exposure on erythrocytes, a major component of the hematological system, of BALB/c mice. Here, we assessed the effect of nose-only WPS exposure for four consecutive weeks on erythrocyte inflammation, oxidative stress, and eryptosis. The duration of the session was 30 min/day, 5 days/week. Control mice were exposed to air. Our results showed that the levels of C-reactive protein, lipid peroxidation (LPO), superoxide dismutase, and total nitric oxide (NO) were significantly increased in the plasma of WPS-exposed mice. The number of erythrocytes and the hematocrit were significantly decreased in WPS-exposed mice compared with the control group. Moreover, there was an increase in the erythrocyte fragility in mice exposed to WPS compared with those exposed to air. The levels of lactate dehydrogenase, LPO, reduced glutathione, catalase, and NO were significantly increased in the red blood cells (RBCs) of WPS-exposed mice. In addition, erythrocytes of the WPS-exposed group showed a significant increase in ATPase activity, Ca2+, annexin V binding, and calpain activity. Taken together, our findings suggest that WPS exposure elevated inflammation and oxidative stress in the plasma and induced hemolysis in vivo. It also caused alterations of RBCs oxidative stress and eryptosis in vitro. Our data confirm the detrimental impact of WPS on erythrocyte physiology.