Question

Discuss Cd toxicity in the kidney and the role of metallothionein in mitigating (or not this toxicity

Answer 1

Answer:- A person with deficiency of iron,calacium or zinc is most probable to absorb cadmium(Cd) in intestines.It affects the upregulation of transport pathways in proximal S1 segment of the kidney tubule as here Cd gets deposited(about 30%).Metallotheonine bound Cd gets degraded into endosomes and lysosomes releasing free Cd into the cytosol where it generate reactive oxygen species and activate cell death pathways.It impairs reabsorption of low molecular weight proteins such as retinol binding protein(Tubular proteinuria).Heavy Cd toxicity can cause fancoi syndrome and may leads to renal failure.It causes defects in protein,glucose,phosphate reabsorption due to oxidative damage to transport proteins and mitochondria.It also affects vit.D metabolism in kidney which further impact on bones(osteomalacia/osteoporosis).

Most of Cd in body bounds to a metal binding protein called Metallotheonie.It plays an importanat role in metabolism and toxcity of Cd.Human adult renal metallothionein has natural content of Cd which induces the resynthesis of this protein upon its catabolism.Metallothionein causes homeostasis of essential metals like copper,zinc,protect against cytotoxicity of Cd and other toxic metals,scavenges free radicals generated in oxidative stress.Induction of Metallothionein decreases Cd toxicity and protect against CdCl2 induced hepatotoxicity but it doesn't protect against acute Cd-metallothionein induced nephrotoxicity.