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Differential activation of Nrf2-Keap1 and NF-kB pathway mediates size-dependent nephrotoxicity of PM_(0.1),PM_(2.5),and PM_(10) particulate matter in mouse model
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作者 Sukhveer Singh hafsa hashmi +5 位作者 Neha Singh Priyanka Goswami Pradeep K Singh Mahadeo Kumar Jyotsna Singh Vikas Srivastava 《Journal of Environmental Sciences》 2025年第12期179-196,共18页
Air pollution is fourth major cause of death worldwide.Recent evidence suggests that particulate matter(PM)may affect kidneys,and the effect may be size and composition dependent.In this study,PM_(0.1),PM_(2.5),and PM... Air pollution is fourth major cause of death worldwide.Recent evidence suggests that particulate matter(PM)may affect kidneys,and the effect may be size and composition dependent.In this study,PM_(0.1),PM_(2.5),and PM_(10)were collected from ambient air and given to BALB/c male mice at 0.25 mg/m^(3) concentration in whole-body inhalation chamber for 28days(6 h/day,5 days/week)to assess their effect on kidney.Physico-chemical characterization of PM particles by SEM,ICP-MS and HPLC showed their various shapes along with the presence of metals and poly aromatic hydrocarbons(PAHs).Following PM exposure,increased serum creatinine levels were observed in animals along with dilated tubules,protein cast deposition,necrosis,immune infiltration,collagen deposition,and shrunken glomeruli in kidney.Immunofluorescence staining showed higher expressions of kidney injury molecule1(KIM-1),cystatin C,β2 microglobulin(β2M),and alpha smooth muscle actin(α-SMA)and fibronectin,suggesting renal injury and fibrosis.PM exposure also increased malondialdehyde(MDA)content and decreased superoxide dismutase 2(SOD2)activity,which in turn leads to induction of inflammation.Mechanistically,PM exposure further inhibited the nuclear factor erythroid 2-related factor 2(Nrf2)signalling and induced kelch-like ECH-associated protein 1(Keap1)and nuclear factor kappa-light-chain-enhancer of activated B(NF-κB).Interestingly,the effect of PM_(2.5)was more severe than PM_(0.1)and PM_(10),leading to higher levels of proinflammatory NF-κB and greater Nrf2 inhibition.Overall,our findings suggested that inhalation exposure to size-segregated PM can cause kidney damage and fibrosis,and PM_(2.5)showed higher toxicity than PM_(0.1)and PM_(10). 展开更多
关键词 Particulate Matter(PM_(0.1) PM_(2.5)and PM_(10)) NEPHROTOXICITY Kidney fibrosis Inflammation Nrf2-Keap1 NF-κB
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Incense smoke(IS)inhalation exposure system:Physicochemical characterization,IS particle deposition and clearance in human airway using MPPD model
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作者 Vyas Kumar hafsa hashmi +2 位作者 Anshita Nasreen Ghazi Ansari Jyotsna Singh 《Particuology》 SCIE EI CAS CSCD 2024年第4期271-285,共15页
Incense smoke(IS)is source of indoor air pollution and key risk for diverse human diseases.Less in-formation is available regarding controlled IS rodent inhalation exposure system and IS particulate matter(PM)depositi... Incense smoke(IS)is source of indoor air pollution and key risk for diverse human diseases.Less in-formation is available regarding controlled IS rodent inhalation exposure system and IS particulate matter(PM)deposition in human airways.Study aimed to demonstrate stable ISPM physicochemical parameters of 10 incense products inside the customized whole body inhalation exposure chamber(without animal)connected to smoke generation unit via aerosol mixing device.IS analyzed for size segregated PM emission,ISPM in vitro aerodynamics(MMAD and GSD determination),fine and ultrafine particle's SEM,SEM-EDX and PAH analysis.Using real life exposure scenario by utilizing MMAD,GSD and PM concentration after Tier 1 exposure assessment as key input parameters,ISPM dosimetry in infant(3 months)and adult(21 years male and female)human airways was calculated using multiple-path particle dosimetry(MPPD 3.04)modeling.Mass median aerodynamic diameter(MMAD)and geo-metric standard deviation(GSD)ranged between 0.55 and 2.10μm and 1.22 to 1.77(polydisperse)respectively.PM1.0 and PM0.1 showed multiple morphology and presence of heavy and trace elements.PAH like acenaphthylene,anthracene,fluorene,naphthalene and phenanthrene were detected(0.84-143.17μg/g).MPPD results showed higher ISPM deposition in pulmonary region and lowest in trachea bronchial region.ISPM deposition in tissue was higher in lower,peripheral lung as compared to upper and central lung tissue.Whole body inhalation exposure system showed stable IS atmosphere(physi-cochemical parameters)indicating the device suitability in future inhalation studies.MPPD ISPM deposition fraction and clearance data showed deep lung penetrating and retention behavior with higher risk in infant followed by female and then male.These modeled particle deposition and clearance data may be useful in risk assessment analysis of IS. 展开更多
关键词 INHALATION Incense smoke Multiple-path particle dosimetry(MPPD) Particle deposition Particulate matter(PM) Mass median aerodynamic diameter (MMAD) Human airway
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