Syllabus Metalionexcesstoxicity-Feexcesstoxicity-Africansiderosis,hemosiderosis, hemochromatosis(bronzediabetes)anddetoxification.Cuexcesstoxicity:Wilson’sdisease andtreatment. Heavymetaliontoxicity:Hg,Pb,Cd,Astoxiceffects–mechanismoftoxiceffects.Heavy metaltoxicitytreatment-chelationtherapy:chelatingagentsforHg,Pb,Cd,Astoxicity. Metalcomplexesasdrugs:cis-plainasanticanceragent:mechanismofactionandside effects;goldcomplexesasantiarthriticdrugs-chrysotherapy.Metalcomplexesindiagnosis- Gdcomplexesinmagneticresonanceimaging(MRI). METALIONEXCESSTOXICITY Ironexcesstoxicity ü ItisduetoaccidentalintakeofFeSO4tabletscausingerosionofthegastrointestinal tract. ü Hemochomatosisisageneticdisorder,depositionofironoccursinvitalorganslike liver,spleen,pancreas,skinetc.Itleadstobronzepigmentationontheskiniscalled bronzediabetes. ü Siderosis(depositionofFeOdustinthelungs)isassociatedwithexcessofiron. ü AfricansiderosisisanironoverloaddisorderfirstobservedamongpeopleofSouthern AfricaandCentralAfrica.Dietaryironoverloadistheconsumptionoflargeamount ofhome-brewedbeerwithhighamountofironcontentinit. Detoxification : Siderophore desferrioxamine is a chelating antidote used for Fe removal Coppertoxicity Copper is a principal component of several metalloproteins and some naturally occurring pigments.Ahealthyadultpossessescopperbetween200to300mgandthehighestamountis concentratedin the locus of brain. Wilson’sdiseaseand Menkes’ kinky hair syndromeare associatedwithageneticdisorderinthemetabolismofcopper. Wilson’sdisease ü In Wilson'sdisease,the copper-content is morethan hundred timesgreaterthanthe normal content. The clinical symptoms of Wilson's disease include hepatic cirrhosis(liverdisease),neurologicaldamage,brownorgreenringsinthecorneaofthe eyes,lackofcoordinationetc.Theexcesscopperisdepositedfirstintheliverandthen inthecentralnervoussystem. ü InWilson'sdisease,thepatientsarefoundtohavethelowlevelsofapoceruloplasmin which is responsible for copper transport. Thus this disease is associated with the geneticfailuretosynthesiseapoceruloplasmin. ü In this disease,there isa large amount of copper in blood stream and it causesthe damage of erythrocyte membrane(hemolyticanemia). Copper is finally deposited in liverandbraindevelopingthehepaticandneurologicsymptoms. Treatment: Toreducethecopperoverload,thechelatingdugslikeNa2Ca(EDTA),D-penicillamine, 2,3-dimercaptopropan-1-olareclinicallyrecommended. Zn-saltsarenowrecommendedforthetreatmentofWilsondisease.Probably,theZn-salts involvetheinductionofthioneinproteinintheintestinalcells.Thethioneinproteintightly bindsthecopper.Thusitinhibitstheintestinaluptakeofcopper.ThemajoradvantageofZn- therapyisitslowtoxicity. .