The effect of lipoic acid on cyanate toxicity in the rat heart.

Background: Cyanate is a uremic toxin formed principally via spontaneous urea biodegradation. Its active isoform, isocyanate, is capable of reaction with proteins by N and S carbamoylation, which influences their structure and function. Sulfurtransferases implicated in anaerobic cysteine transformation and cyanide detoxification belong to the enzymes possessing SH groups in their active centers. The present studies aimed to demonstrate the effect of cyanate and lipoic acid on the activity of these enzymes as well as on the level of antioxidants and prooxidants in the rat heart.

Methods: Wistar rats, which received intraperitoneal injections of cyanate and lipoic acid alone and in combination were sacrificed 2.5 h after the first injection. The hearts were isolated and homogenized in phosphate buffer and next biochemical assays were performed comprising determination of the level of glutathione, malondialdehyde and sulfane sulfur and the activity of antioxidant enzymes as well as glutathione S-transferase and gamma glutamyl transferase.

Results: Sulfurtransferases and glutathione S-transferase were deactivated by cyanate treatment. It was accompanied by the decreased level of glutathione and sulfane sulfur and the increased level of reactive oxygen species and malondialdehyde. In parallel, antioxidant enzymes: catalase, glutathione peroxidase and gamma glutamyl transferase were activated under such circumstances. Lipoic acid, administered in combination with cyanate prevented the decrease in the level of glutathione and reduction of a pool of sulfane sulfur-containing compounds, concomitantly preserving the activity of antioxidant enzymes.

Conclusions: Since uremia, characterized by the elevated cyanate/isocyanate level, is accompanied by frequent cases of cardiovascular diseases, the addition of lipoic acid to the therapy seems promising in prophylaxis of heart diseases in uremic patients.