Arsenic Thyrotoxicity And The Effect Of Arsenic On Thyroid Endocrine System

Arsenic(As)is a toxic metalloid widely distributed in the environment.Its presence in soil,food,water and air leads to human exposure to As.Furthermore,increasing anthropogenic activities have increased As concentrations in the environment,resulting in more human exposure to As.Hitherto,over 200 million persons worldwide might be chronically exposed to As from drinking water at concentrations above the WHO safety standard of 10 ?g L-1.Chronic exposure to As results in a series of health problems,including cancers such as kidney,bladder,skin,lung cancers,and non-cancerous diseases including cardiovascular,peripheral neuropathy,obstructive pulmonary disease.These diseases probably can be attributed to As-induced immune response.Investigators pointed out that As can damage immune system,rendering them susceptible to pathogenic challenge.It is known that endocrine system modulates the external contamination effects on the immune system.There many studies have investigated As toxicity on adrenal endocrine system and gonadal endocrine system,however,thyroid endcrine system has received limited attention.We will focus on the effect of As on thyroid endcrine system.The main results were as follows:(1)Arsenic(As)contamination in aquatic environment adversely impacts aquatic organisms.The present study assessed the toxicity of different As species and concentrations on bighead carp(Hypophthalmichthys nobilis)at early life stage,a major fish in Yangtze River,China.We measured the changes in embryo and larvae survival rate,larvae aberration,concentrations of thyroid hormone thyroxine,and transcription levels of thyroid hormone receptors(TRs)in fish larvae after exposing to arsenite(AsIII)or arsenate(AsV)at 0,10,30,50,100,or 150 ?g L-1 for 78 h.As concentrations<150?g L-1 had limited effect on embryo survival rate(6-8%inhibition),but larvae survival rate decreased to 53-57%and larvae aberration rate increased to 20-24%after As exposure.Moreover,thyroxine levels elevated by 23%and 50%at 100 ?g L-1 AsIII and 150 ?g L-1 AsV.Besides,As? and AsV decreased the transcriptional levels of TRa by 72 and 53%,and TR? by 91 and 81%at 150 ?g L-1 As.Our data showed that As? and AsV had limited effect on carp embryo survival,but they were both toxic to carp larvae,with As? showing more effect than AsV.As concentrations<150 ?g L-1 adversely influenced the development of bighead carp larvae and disturbed their thyroid hormone homeostasis.(2)Aquatic environment polluted by arsenic(As)posed threat to fish,and studies pointed that As have the potential to disrupt thyroid hormone homeostasis.In this study,we explored the effect of short-term exposure of arsenite(AsIII)on thyroid endocrine system in zebrafish.We measured As concentrations,speciation and thyroxine(T4)in the whole zebrafish,oxidative damage(MDA)in liver,and gene transcription in hypothalamic-pituitary-thyroid(HPT)axis in brain and liver tissues of zebrafish after exposing to different AsIII treatments for 48 h.Result indicated that zebrafish exposure to As? increased inorganic As to 0.46-0.72 mg kg-1,induced oxidative damage with MDA augment 1.6 times.As? exposure increased T4 levels by 1.3-1.4 times and modulated gene transcription in HPT axis.As? caused oxidative damage,affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish.(3)Drinking water polluted by arsenic(As)is a worldwide issue,it posed threat to people health.As toxicity on thyroid endocrine system has attracted more attention.In our study,we assessed the the impact of different concentrations of arsenic(AsV and As?)on the thyroid hrormone(T4)and HPT aixs related gene transcription after expsed for different times.This study manifested that 10 ?g L-1 AsIII slightly elevated the T4 content after exposure for 1 week.AsV and AsIII exert more toxicity on T4 content after long term exposure,10 ?g L-1 AsV increased T4 levels by 11%and 13%after exposure for 4 and 8 weeks,10 ?g L-1 As? increased T4 content by 10.7%and 10.8%after exposure for 4 and 8 weeks,100 ?g L-1.Howe,ver,AsIII displayed different results,it inhibited T4 content by 10.3%,and elevated T4 content by 29%.Furthermore,we also found the As had a significantly effect on HPT axis related gene transcription.Besides,we detected that 100 ?g L-1 AsIII induced thyroid gland damage.It demonstrated that As disrupted T4 homeostasis,influenced the related gene transcription and damaged the thyroid glands.