title: Humic acid-induced echinocyte transformation in human erythrocytes: characterization of morphological changes and determination of the mechanism underlying damage.
abstract: Blackfoot disease (BFD) is a peripheral arterial occlusive disease found among human inhabitants along the southwest coast of Taiwan. Well water used for drinking and cooking contains humic acid (HA), which may be a possible etiological factor. In this study, HA toxicity was investigated in human erythrocytes and was found to induce echinocytic formation. Morphological changes occurred in both a concentration- and time-dependent fashion. The presence of HA was also observed to facilitate the loading of erythrocytes with excess Ca(2+) (1 mM), which may have occurred following permeability changes in cell membranes, leading to echinocytic transformations. Sodium dodecyl sulfate (SDS) gel electrophoresis indicated that echinocyte formation was due to the oxidation of normal membrane proteins that were replaced by high-molecular-weight proteins. Humic acid also induced hemoglobin oxidation in erythrocytes. Data show that oxidative stress generated by HA as well as direct effects were exerted on the cytoskeleton of erythrocytes, and these may be significant factors in the etiology of BFD.
authors.affiliation: Department of Nutrition, China Medical College, Taichung, Taiwan, Republic of China.
authors.forename: Y C
authors.initials: YC
authors.lastname: Hseu
authors.forename: F J
authors.initials: FJ
authors.lastname: Lu
authors.forename: L R
authors.initials: LR
authors.lastname: Engelking
authors.forename: C L
authors.initials: CL
authors.lastname: Chen
authors.forename: Y H
authors.initials: YH
authors.lastname: Chen
authors.forename: H L
authors.initials: HL
authors.lastname: Yang
mesh_terms: D000740:Anemia / Q000139:chemically induced; D015220:Calcium Channels / Q000187:drug effects; D002462:Cell Membrane / Q000502:physiology; D002614:Chelating Agents / Q000633:toxicity*; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006812:Humic Substances / Q000633:toxicity*; D008565:Membrane Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D016491:Peripheral Vascular Diseases / Q000139:chemically induced; D010539:Permeability
chemical_list: D015220:Calcium Channels; D002614:Chelating Agents; D006454:Hemoglobins; D006812:Humic Substances; D008565:Membrane Proteins