Exploring Mechanisms Of Damage By Lead Induced Disturbance Of Selenium Homeostasis

As a heavy metal generally considered to be toxic,lead(Pb)displays the destruction of the antioxidant system and causes oxidative damage through animal,cellular and molecular evidences.Lead still belongs to one of the most commonly environmental pollutants because of its large consumption in several branches of industry,and could spread into human bodies through the food chain1 and then accumulate in kidney,liver,bone and nervous system organs,causing renal impairment,hepatic steatosis and hyperplasia,hematological disorders,cognitive dysfunction and other harmful health problems.Selenium(Se)plays vital roles in protection from oxidative stress caused by toxic materials such as lead.Little studies have demonstrated if selenium homeostasis could be disturbed by lead,resulted in oxidative stress and other harmful damages so far This study investigated mechanisms of lead-induced disturbance of selenium homeostasis both at the animal?cellular and molecular levels.This paper includes the following five chapters:The first chapter briefly introduced toxic effects of lead after entered into human bodies,and the relationship between Selenium and lead toxicity.Then,the memods and research purposes,contents and significance of this paper were brieny described.Chapter two studied changes of selenoprotein levels and functions in tissues and cells after lead exposure on animal levels.Mice with 4-week-old were drunk increasing Pb concentrations(0,1,2 and 4 g/L)of water for 4 weeks,respectively.Total Se concentrations in blood plasma measured with ICP-MS,contents of Gpx3 and selenoprotein P(SelP)in blood plasma tested by ELISA and mRNA levels of key selenoproteins in mice livers,kidneys determined using qPCR were significantly inhibited at higher lead concentrations(P<0.05),including SelP and Gpx3,two key proteins to keep Se homeostasis and distribution in bodyChapter three evaluated molecular mechanisms of oxidative stress induced by lead at the cellular levels.We measured biomarkers of oxidative tress in liver and kidney,including an increase of malondialdehyde(MDA)content and contents of reduced glutathione(GSH).Results told us lead exposure bringed oxidative stress in mice livers and kidneys.In Chapter four,to further confirm the hypothesis that lead may disturb Se homeostasis through affecting SelP and Gpx3,we investigated molecular mechanisms of toxic effects of lead on SelP and Gpx3.Results showed lead statically quenched SelP fluorescence by means of tightly binding to structural domain of SelP and Gpx3,and the conformational investigation of SelP and Gpx3indicated lead changed the secondary structure of SelP and Gpx3.This work presents molecular mechanisms disturbance of Se homeostasis in mice livers caused by lead combined in vivo and in vitro studies,and contributes to a better understanding of lead toxicity on human health.