title: Aluminum citrate inhibits cytotoxicity and aggregation of oxalate crystals.
abstract: Calcium oxalate monohydrate (COM), which represents a major component of kidney stones, is an end metabolite of ethylene glycol. COM accumulation has been linked with acute renal toxicity in ethylene glycol poisoning. COM injures the kidney either by directly producing cytotoxicity to the kidney cells or by aggregating in the kidney lumen leading to the blockage of urine flow. The present studies were designed to examine whether aluminum citrate could reduce the toxicity of COM. Toxicity was determined in human proximal tubule cells by leakage of lactate dehydrogenase or uptake of ethidium homodimer and in erythrocytes by degree of hemolysis. Aluminum citrate significantly inhibited the leakage of lactate dehydrogenase from human proximal tubule cells and protected against cell death from COM. The inhibitory effect of aluminum citrate was greater than that of other citrate or aluminum salts such as sodium citrate, aluminum chloride, calcium citrate, ammonium citrate or potassium citrate. Aluminum citrate significantly inhibited the aggregation of COM crystals in vitro and decreased red cell membrane damage from COM. Aluminum citrate appeared to directly interact with COM, but not with the cell membrane. As such, aluminum citrate reduced the cytotoxicity by a physico-chemical interaction with the COM surface, and not by dissolving the COM crystals. These studies suggest that aluminum citrate may protect against tissue damage that occurs with high levels of oxalate accumulation, especially in ethylene glycol poisoning and possibly in hyperoxaluric states.
authors.affiliation: Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
authors.forename: Chungang
authors.initials: C
authors.lastname: Guo
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: McMartin
mesh_terms: D000818:Animals; D002129:Calcium Oxalate / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D019343:Citric Acid / Q000494:pharmacology*; D004347:Drug Interactions; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D019855:Ethylene Glycol / Q000037:antagonists & inhibitors* / Q000506:poisoning / Q000633:toxicity; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051381:Rats; D051437:Renal Insufficiency / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D012995:Solubility
chemical_list: D002129:Calcium Oxalate; D019343:Citric Acid; D007770:L-Lactate Dehydrogenase; D019855:Ethylene Glycol; C455846:aluminum citrate