Effect of Cyclosporine A on Total Homocysteine Level in a Rabbit Model

Abstract

Background Moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Cyclosporine (CsA) has been suggested to interfere with folate-assisted remethylation of homocysteine, thus causing hyperhomocysteinemia. But, this issue is controversial. In this experimental study, we attempted to determine the association between CsA administration and total homocysteine levels. Working with rabbits that have normal creatinine levels, we obviated the misleading effects of renal functional variations, which are the most important confounding factors affecting total homocysteine level. Methods Male New Zealand rabbits fed a standard quantity of diet received 10 days of subcutaneous injections of 10 mg/kg per day CsA. After these loading doses, CsA (20 mg/kg) was administered subcutaneously three times a week for 20 days. After first 30 days, the rabbits were followed for another 30 days without CsA therapy. Plasma creatinine, BUN, and total homocysteine levels were measured on days 0, 10, 30, and 60. Results There were no significant changes in BUN results on days 0, 10, 30, and 60 ( P > .05). There was a slight, but significant, increase in mean creatinine levels during CsA administration ( P < .01). However, the mean creatinine levels remained in the normal ranges during the 60 days of study. No significant changes were observed in total homocystein levels ( P > .05) compared to baseline, 10-, 30-, and 60-day values. Conclusion Our experimental research minimized confounding factors. It showed that CsA does not increase total homocysteine levels, confirming clinical studies that reported no association between CsA and total homocysteine.