Effects Of Alumina Nanopowder On Organ Damage And Allergic Asthma In Mice

Alumina nanopowder(nAl2O3)is widely used in electronics,chemical and chemical engineering,insulating materials,ceramics,catalysts and their carriers,aerospace,rubber and other fields due to a series of excellent feature such as high strength,high hardness,heat resistance and corrosion resistance.The inclusive application of nAl2O3 has gradually attracted people’s attention to the environmental and health risks that may arise.Some basic researches have shown that nAl2O3 can enter human body and other organisms through various ways,thus producing certain toxic effects such as neurotoxicity,ecotoxicity,reproductive and developmental toxicity,immunotoxicity and genotoxicity,thereby inducing different effects on the environment and organisms.Most studies have shown that inhalation of toxic metals and metal oxide nanomaterials can lead to lung cancer,while inhalation is the primary exposure route for nanomaterials.Related studies have shown that exposure of nanomaterials such as carbon nanotubes and titanium dioxide nanoparticles can aggravate the further deterioration of allergic asthma,resulting in lung function damage in mice.However,experimental studies on the toxicity of nanomaterials are not sufficient,so further exploration and further research are needed.Studies on the respiratory toxicity of nAl2O3 with different concentrations,the association between nAl2O3 and allergic asthma,and the underlying mechanisms have not been reported in the literature by simulating the way of continuous inhalation exposure.In this study,Balb/c mice with specific pathogen-free(SPF)grades were adaptively reared for 5 days.0.5,5,50 mg/kg/day nAl2O3 was exposed by intratracheal instillation,and 50 mg/kg/day Vitamin E(Vit E)was gavaged for 21 days.The experimental results showed that compared with the control group,the exposure of 0.5 mg/kg/day nAl2O3 increased ROS(reactive oxide species)levels and decreased GSH(glutathione)contents in mice lung;5 mg/kg/day and 50 mg/kg/day nAl2O3 significantly increased ROS in lung,spleen,liver and kidney of the mice,and significantly decreased the GSH contents in lung and liver.In addition,the airway remodeling including airway lumen shrinkage,lung tissue fibrosis,and bronchial wall thickening as well as the infiltration of inflammatory cells in BALF appeared in mice lung.The treatment of Vit E significantly reduced ROS levels in liver,effectively restored GSH activity in lung,and alleviated lung airway remodeling and inflammation.It is concluded that the exposure of nAl2O3 not only causes lungdamage and inflammation,but also can pass through the alveolar-capillary barrier,thereby entering the blood circulation of the body,causing oxidation of organs such as the spleen,liver and kidney damage.Besides,oxidative stress is one of the main ways in which nAl2O3 induces damage in various organs of mice.Based on the above research,Balb/c mice with SPF grades were randomly divided into 9 groups of eight each.The mice were instilled intratracheally with 0.5,5,50 mg/kg/day nAl2O3 suspensions once every two days,gavaged with 100 mg/kg/day Vit E every day and sensitized with 50 μg OVA plus 1.75 mg Al(OH)3 in 300 μL saline by intraperitoneal injection on day 7,14,and 21.Then mice were followed by an aerosol challenge of 1%OVA(30 min/day)from days 24 to 30.The study detected mice lung function,pathological changes of lung tissue,total immunoglobulin-E(T-IgE)contents in serum,the expression of T-bet,GATA-3,Foxp3,RORγt mRNA in lung tissue,cytokines y-interferen(IFN-y),interleukin-4(IL-4),IL-10,IL-17A,transcriptional growth factor-β(TGF-β),IL-1β and IL-6 levels,inflammatory cell numbers,and ROS and GSH levels in lung tissue,exploring the relationship between nAl2O3 exposure and allergic asthma and its underlying mechanisms.The experimental results showed that the significant increase in serum T-IgE contents and airway hyper-rsponsiveness(AHR)levels in the OVA group compared with the control group,indicated that the establishment of the allergic asthma model was successful.Under the sensitization and challenge of OVA,the levels of T-IgE in the exposed group of nAl2O3 significantly increased;the level of oxidative stress significantly increased,the phenomenon of airway remodeling and the inflammatory cells significantly increased;the expression levels of GATA-3 and RORyt mRNA significantly increased;cytokines IL-4,IL-17A,TGF-β,IL-1β and IL-6 levels significantly elevated,IFN-y and IL-10 levels significantly reduced;expiratory resistance(Re)and inspiratory resistance(Ri)significantly elevated,and compliance(Cldyn)in mice lung significantly decreased.In summary,the exposure of nAl2O3 not only caused oxidative damage and inflammatory reaction in the lungs of mice,but also caused certain damage to the spleen,liver and kidney.the exposure of nAl2O3 can cause oxidative damage on various organs.The study found that nAl2O3 promoted asthma-like symptoms in mice by imbalance of Th1/Th2 and Treg/Th17 immune responses as well as the increase of oxidative stress levels,thereby aggravating the deterioration of allergic asthma.Vitamin E can alleviate the deterioration of allergic asthma in mice by reducing the increase levels of oxidative stress and inflammatory response.These studies may provide a theoretical basis and reference for the safety application of nAl2O3 and the investigation of the pathogenesis of allergic asthma.