Pentachlorophenol-induced cytotoxicity in human erythrocytes: enhanced generation of ROS and RNS, lowered antioxidant power, inhibition of glucose metabolism, and morphological changes.

ABSTRACT

Pentachlorophenol (PCP) is a class 2B human carcinogen that is used as an insecticide, herbicide, and wood preservative. PCP is rapidly absorbed and enters the blood where it can interact with erythrocytes. We have examined the effect of PCP on human erythrocytes. Treatment of erythrocytes with PCP increased the intracellular generation of reactive oxygen and nitrogen species. It also increased lipid and protein oxidation accompanied by decrease in glutathione levels and total sulfhydryl content. The activities of all major antioxidant enzymes were altered. The antioxidant power was significantly impaired resulting in lower free radical quenching and metal reducing ability of the PCP-treated cells. PCP exposure also inhibited the activities of enzymes of glycolysis and pentose phosphate shunt, the two pathways of glucose metabolism in erythrocytes. Heme degradation was enhanced leading to the release of free iron. Incubation of erythrocytes with PCP caused significant cell lysis suggesting plasma membrane damage which was also evident from inhibition of bound enzymes. Scanning electron microscopy of erythrocytes confirmed these biochemical results and showed that PCP treatment converted the normal biconcave discoids to echinocytes and other irregularly shaped cells. Thus, PCP induces oxidative and nitrosative stress in erythrocytes, alters the enzymatic and nonenzymatic antioxidant defense systems, inhibits glucose metabolism, and causes significant modifications in cellular morphology.