Study On Biological Toxicity Evaluation And Molecular Mechanism Of Tin Sulfide Nanoflower

We selected tin sulfide nanoflowers（SnS₂ nanoflowers,SnS₂ NFs）as the research object,using traditional methods of toxicology to observe the toxical effects of SnS₂ NFs after repeated exposure,revealing the potential target organs of SnS₂ NFs,and the effects of SnS₂ NFs on body weight,organ coefficient of mice,and the clinical biochemical indexes on histopathological effects;in addition,we used modern omics technology,including genomics and proteomics technology to discuss the toxic mechanism of SnS₂ NFs at the gene and protein level,and ultimately provide theoretical basis for safety evaluation,toxicity monitoring and intervention of SnS₂NFs.Results are listed as follows:1.Synthesis and physicochemical characterization of SnS₂ NFs.Three different sizes of SnS₂ NFs were synthesized by hydrothermal method.Structure and morphology of nanometer spend using X-ray diffractometer（XRD）,scanning electron microscope（SEM）,transmission electron microscopy（TEM）observation confirmed that the particle size of SnS₂ NFs.The results showed that all the samples were hexagonal SnS₂,and the particles were flower structure of about 50,80 and 200 nm in diameter.The flower structure consisted of dozens of nano-sheets interconnecting to form a three-dimensional structure.The samples of 50 nm SnS₂ were analyzed with nano particle size,zeta potential and molecular weight analyzer.The results showed that the main particle size of 50 nm SnS₂ in deionized water was 116 nm and that in phosphate buffer brine was 192 nm.2.SnS₂ NFs（50-200 nm,250-1000 mg/Kg BW）gavage to ICR mice daily for 14 days,and the accumulation of element tin in various organs was determined by inductively coupled plasma mass spectrometry（ICP-MS）.The results showed that SnS₂ NFs was mainly accumulated in the liver,kidney,spleen,testis and brain.Medium and high doses of SnS₂ NFs（50 nm）triggered dose-dependent liver inflammation and apoptosis.The expression of metabolic genes in liver tissues also changed,supporting the liver cell phenotype associated with SnS₂ NFs.3.SnS₂ NFs（Dosage:2.5,5,and 10 mg/kg BW;Particle size:50 nm）gavage to ICR mice daily for 90 days.The results showed that tin could be accumulated in the kidney,the serum biochemical indices related to renal function Cr increased,and BUN and UA excreted less.SnS₂ NFs exposure could cause oxidative damage in renal tissue of mice,resulting in morphological changes,renal dysfunction and inflammatory response.4.SnS₂ NFs（Dosage:5,10,and 50 mg/Kg BW;Particle size:50 nm）gavage to ICR mice daily for 60 days,and the molecular mechanisms of neurotoxicity,oxidative stress,memory function related genes and signal transduction factors were studied.This study provides a theoretical basis for neurotoxicity assessment of long-term low dose exposure of SnS₂ NFs.The results showed that SnS₂ NFs could enter brain tissue through the blood-brain barrier,causing oxidative damage and pathological changes in the brain tissue of mice.By changing the gene expression levels of oxidative stress,metabolism and signal transduction related cytokines,it could lead to brain injury in mice.5.ICR mice were injected into abdominal cavity with SnS₂ NFs（50-200 nm,0.38-38mg/Kg BW）every day for 28 days,and the damage of reproductive system of mice was studied.The results showed that small particle size of SnS₂ NFs could cross the blood-testis barrier of mice and enter the testicular tissue,resulting in the oxidative damage of mouse testicular tissue.The high dose of SnS₂ NFs exposure resulted in decreased sperm quality of mice,decreased AMH secretion of male hormone,decreased tight junction protein,and decreased resistance of the blood-testis barrier.