Mesna as a Nonvitamin Intervention to Lower Plasma Total Homocysteine Concentration: Implications for Assessment of the Homocysteine Theory of Atherosclerosis

¹ Department of Physiology and Pharmacology, University of Western Ontario
² Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario
³ Robarts Research Institute
⁴ Division of Nephrology, University of Western Ontario

^* To whom correspondence should be addressed. E-mail: Andrew.House{at}lhsc.on.ca.

	Abstract

Elevated plasma total homocysteine is independently associated with atherosclerosis. Recent randomized trials show that vitamins lower total homocysteine but do not prevent cardiovascular events, suggesting the need for nonvitamin therapies to evaluate whether a causative relationship exists. Mesna (sodium 2-mercaptoethanesulfonate) is a thiol-containing drug capable of liberating homocysteine bound by disulfide bonds to proteins, facilitating its excretion. The effect of oral mesna on total homocysteine has not been evaluated and was the objective of this study. Eleven healthy volunteers received vehicle or 10 mg/kg mesna in random order, after which serial blood and urine samples were collected over 4 hours. Plasma total homocysteine decreased by 24.2% (P < .0001) following mesna. Urinary homocysteine excretion was significantly greater with mesna (3.9 ± 2.4 µmol) compared to vehicle (0.4 ± 0.1 µmol), P < .01. Oral mesna decreases plasma total homocysteine and is a potential nonvitamin treatment for assessing the homocysteine theory of atherosclerosis.