Seeds of Toxicity? Erythrocytes and Lead-Associated Kidney Damage

In this study the researchers hypothesized that lead exposure increases the number of PS-tagged erythrocytes, which are then consumed by the proximal tubular epithelial cells in the kidney. They further hypothesized that iron from the erythrocytes accumulates in the kidney cells, where it triggers the formation of reactive oxygen species, the first step in oxidative damage. The ultimate biological outcome of toxic exposures is frequently a combination of two factors—individual responses of multiple tissues and, subsequently, complex interactions of altered tissues—says study coauthor Jin-Ho Chung, a professor in the College of Pharmacy at Seoul National University. “We considered that lead-associated nephrotoxicity must be interpreted in the context of systems biology, rather than as sole and isolated damage to the kidney,” Chung says. Chung and his colleagues conducted a series of in vitro experiments with HK-2 cells5 and erythrocytes derived from volunteers’ blood samples. They showed that, in the absence of erythrocytes, the viability of lead-exposed HK-2 cells was not significantly different from the viability of unexposed HK-2 cells. A separate experiment demonstrated increased PS externalization in lead-exposed erythrocytes. And when lead-exposed erythrocytes were co-cultured with unexposed HK-2 cells, the HK-2 cells not only phagocytized the erythrocytes, but also showed increased production of reactive oxygen species, diminished viability, and greater expres...
Source: EHP Research - Category: Environmental Health Authors: Tags: Featured News Science Selection Cardiovascular Health February 2015 Lead Metals Urinary Health Source Type: research