Oral Halloysite Nanotubes-induced Subacute Toxicity In The Stomach And Small Intestines Of Mice And Recovery

Halloysite(Al2Si2O5(OH)4 nH2O)nanotubes(HNTs)have been widely used in medical industry as a drug or drug carrier.However,their adverse effects on gastrointestinal tract of mammals is still unknown.This thesis focuses on the toxicity and recovery of oral administration of the purified HNTs on the stomach and small intestine of mice.The results show that oral low dose of HNTs(5 mg/kg BW)for 30 consecutive days promoted the growth of mice with no obvious toxic effects on the stomach and small intestine of mice,and.The promotive effect on mouse growth disappeared after cessation of oral administration of HNTs.Oral HNTs at high dose(50 mg/kg BW)for 30 days induced obvious toxicity in the stomach and small intestine of mice and reduced mouse growth.Oral administration of HNTs at high dose resulted in a large accumulation of Al and Si in the stomach and small intestine of mice,and reduced water intake and food intake,and increased the coefficients of stomach and small intestine.In addition,oral administration of HNTs at high dose caused severe pathological changes in the stomach and small intestine of mice,including atrophy,erosion and infiltration of inflammatory cells in the stomach and small intestine mucosa,accompanied by the decreases of serum gastrin and pepsinogen levels and the increases of lymphocyte and leukocyte in the blood.The histopathological changes were caused by the decreases of the expression of antioxidant enzymes GSH-PX and SOD,and the increases of the MDA level and the expression of inflammatory factors INOS and COX-2 in gastrointestinal and small intestinal tissues.These results suggest that oral HNTs at high dose can induce oxidative stress in gastrointestinal and small intestinal tissues of mice,which further leads to inflammatory reaction in gastrointestinal and small intestinal tissues.Further studies show that oral HNTs-induced oxidative stress and inflammatory reaction in the stomach and small intestine at high dose were not observed after a 30-days recovery period.The accumulation of Al and Si in the stomach and small intestine tissues were cleared out of the mice after a 30-days recovery period.The findings provide the evidence that oral HNTs-induced acute toxicity in the stomach was reversible.Present results indicate the safety of HNTs in the applications in mice at low doses(5×5 mg/kg B W).However,caution should be taken when applying IHNTs at high doses(≥50 mg/kg BW).Therefore,more attention should be payed to the toxicity of HNTs in the gastrointestinal tract.