Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
This AOP links thiol oxidation to CKD via oxidative and mitochondrial stress. Within the nephron, the proximal tubule is especially susceptible to injury from oxidative chemicals, as they can cause mitochondrial damage, which in turn can result in impairment of active and secondary transport, as well as in cell death. CKD is characterized by a progressive loss of renal function, the onset of which is initiated and/or accelerated by other factors such as diabetes, high blood pressure or exposure to nephrotoxic chemicals. Given its high energy demand for active transport, the proximal tubule is especially susceptible to injury from oxidative chemicals and mitotoxins.
