Kenneth E. McMartin, Ph.D.
Professor
Department of Pharmacology, Toxicology and Neuroscience
Ph.D., 1977, University of Iowa

Major Research Interests:
Mechanisms of toxicity of alcohols and glycols, renal toxicology, regulation of folate metabolism, tissue culture, folate transport.

My research focuses on determining the mechanism by which a substance is toxic and utilizing this information to develop improved therapies for poisonings. For example, my laboratory discovered and has developed fomepizole, which is now the standard antidote used in treating methanol and ethylene glycol poisonings.

Ingestion of substances like antifreeze that contain ethylene glycol can produce a severe poisoning that includes damage to the kidney and to capillaries in other organs such as the brain. Tissue damage results because ethylene glycol is metabolized to oxalic acid, which accumulates as crystals of calcium oxalate in the kidney and endothelium of blood vessels. We are studying how calcium oxalate produces the damage by investigating its mechanisms of cell death in kidney and endothelial cells in culture. We are examining how calcium oxalate inhibits mitochondrial function, since the loss of mitochondrial energy production induces cell death. Calcium oxalate can also accumulate in kidney stone disease. We are studying how aluminum citrate blocks the toxicity of calcium oxalate and whether it may be useful in treating the kidney damage in ethylene glycol poisoning and in kidney stone disease.

Chronic alcohol ingestion is associated with deficiencies of many vitamins, especially of folate. We are studying why folate deficiency results from chronic ethanol ingestion. We have shown that ethanol consumption increases urinary excretion of folate, so are studying the mechanisms by which folate is transported across the kidney cell membrane. The roles of specific folate transport proteins and cellular regulatory elements are studied using both pharmacologic and genetic manipulations.

Diethylene glycol (DEG) is a solvent that has led to many mass poisonings when it has been mistakenly used in liquid drug formulations and has recently been found in imported toothpastes in the US. The mechanism by which DEG produces liver and kidney toxicity is not known and there is no accepted treatment. We are studying the metabolism of DEG and the toxicity of its metabolites in order to determine the mechanism for the toxicity of DEG. Such information will then be used to design therapies for DEG poisonings

Selected Recent Publications:

Brent J, McMartin KE, Phillips S, Aaron C, Kulig K. Fomepizole for the treatment of methanol poisoning. New Engl J Med 444: 424-9, 2001.

McMartin KE, Wallace KB. Calcium oxalate monohydrate, a metabolite of ethylene glycol, is toxic for rat renal mitochondrial function. Toxicol Sci. 84: 195-200, 2005.

Guo C, McMartin. Aluminum citrate inhibits cytotoxicity and aggregation of oxalate crystals. Toxicology. 230: 117-25, 2007.

Romanoff RL, Ross DM, McMartin, KE. Acute ethanol inhibits renal folate transport, but subacute ethanol up-regulates folate transport proteins in rats and human cells. J. Nutr.137:1260-5, 2007.

Guo C, Cenac TA, Li Y, McMartin KE. Calcium oxalate, and not other metabolites, is responsible for the renal toxicity of ethylene glycol. Toxicol Lett. 173: 8-16, 2007.

Contact Info:
Dr. Kenneth McMartin
Professor
Department of Pharmacology, Toxicology and Neuroscience
Louisiana State University Health Sciences Center
1501 Kings Highway
Shreveport, LA 71130-3932
318-675-7871
kmcmar@lsuhsc.edu