Toxic Effects Of ZnO NPs On Juvenile Male Rats And Its Mechanism Based On Oxidative Stress And Endoplasmic Reticulum Stress

Zinc oxide nanoparticles(ZnO NPs)have a wide range of applications in the fields of medicine,cosmetics,and food packaging due to their small size(<100 nm),good biocompatibility and antibacterial properties,especially in infants and juvenile children in recent years.And the existence of ZnO NPs found in children’s products has caused people to worry about their safety.Children are in the stage of rapid growth and development.They are not simply a "shrinked version" of adults.Many organs such as the liver,kidneys and reproductive organs have not matured,and are highly sensitive to external toxicants,and they are likely to be affected Normal organ function after being an adult.At present,most nano-toxicology studies are based on adult mature individuals,and toxicology studies for the stage from weaning to sexual maturity are insufficient.Therefore,it is urgent to evaluate the safety risks of nanoparticles to children.This paper explored the toxicity of exposure to different doses of ZnO NPs on the testis,liver,and kidney of juvenile male Sprague Dawley(SD)rats,as well as investigating the mechanism based on oxidative stress and endoplasmic reticulum response.The antioxidant N-Acetyl-L-cysteine(NAC)and the endoplasmic reticulum stress inhibitor Salubrinal(Sal)are further used to explore these two inhibitors alleviate the toxicity of ZnO NPs to juvenile rats and verify the above mechanism.The contents of each chapter are as follows:The first chapter reviews the effects of nanomaterials on the reproductive organs(testis)and main metabolic organs(liver and kidney)of juvenile mammals.The second chapter explores the effect of oral exposure of ZnO NPs on the testis of male juvenile rats and its mechanism.Male rats on the 21 st day after birth were orally exposed to 68,203,and 610 mg/kg ZnO NPs for 28 consecutive days.It was found that exposure to ZnO NPs did not affect the time of sexual maturity,but it could cause testicular damage in male rats,including germ cell apoptosis,spermatogenesis inhibition,and testosterone reduction.At the same time,ZnO NPs activated oxidative stress and endoplasmic reticulum stress in the testis.In addition,after intragastric administration of 610 mg/kg ZnO NPs,the antioxidant NAC or endoplasmic reticulum stress inhibitor Sal was injected intraperitoneally.It was found that both NAC and Sal reduced the male reproductive toxicity caused by ZnO NPs.NAC reduces the level of ROS and further alleviates the endoplasmic reticulum stress,while Sal plays a more obvious role in alleviating the endoplasmic reticulum stress.The research proved that oral exposure of ZnO NPs can activate oxidative stress and endoplasmic reticulum stress,thereby impairing the normal structure and function of the testis of male juvenile rats,and ultimately affecting male fertility.The third chapter explores the effect of oral exposure of ZnO NPs on the liver of male juvenile rats and its mechanism.Male rats on the 21 st day after birth were continuously orally exposed to 68,203,and 610 mg/kg ZnO NPs for 28 days to explore the effect of ZnO NPs on the liver of juvenile rats.The results showed that the liver organ coefficient of rats increased after exposure to ZnO NPs,and structural damage and changes in liver function indexes AST,ALT,and ALP occurred.At the same time,ZnO NPs can cause oxidative damage in the liver and activation of endoplasmic reticulum stress.In order to further verify the role of oxidative stress and endoplasmic reticulum stress in the toxic process,follow-up experiments were performed on male juvenile rats by intraperitoneal injection of antioxidant NAC or endoplasmic reticulum stress inhibitor after intragastric administration of 610 mg/kg ZnO NPs Sal.It was found that both NAC and Sal alleviated the liver damage caused by ZnO NPs.NAC eliminates excessive ROS induced by ZnO NPs and relieves endoplasmic reticulum stress,while Sal has a similar effect,which can reduce oxidative damage and significantly inhibit endoplasmic reticulum stress.The research proved that oral exposure of ZnO NPs can activate oxidative stress and endoplasmic reticulum stress,thereby impairing the normal structure and function of the liver in juvenile rats,thereby causing liver damage in juvenile rats.Chapter 4 explored the effects of oral exposure of ZnO NPs on the kidneys of juvenile male rats and its mechanism.Male SD rats with PND 21 were orally exposed to 68,203,and 610 mg/kg of ZnO NPs for 28 days.The results showed that ZnO NPs caused renal histopathological damage and renal function damage in a dose-dependent manner,and activated oxidative stress and endoplasmic reticulum stress.Supplementing antioxidant NAC and endoplasmic reticulum stress inhibitor Sal found that both NAC and Sal can significantly reduce the renal toxicity caused by ZnO NPs.NAC obviously eliminates oxidative damage and relieves endoplasmic reticulum stress to a certain extent.Sal’s effect on reducing endoplasmic reticulum stress is far better than reducing oxidative stress.The research proved that ZnO NPs generate ROS and trigger oxidative stress,and then activate endoplasmic reticulum stress,which causes kidney damage in juvenile rats.