Mechanisms underlying the cardioprotective effect of l-cysteine

Abstract

In many tissues the availability of L-cysteine is a rate-limiting factor in glutathione production, though this has yet to be fully tested in heart. This study aimed to test the hypothesis that supplying hearts with 0.5 mM L-cysteine would preserve glutathione levels leading to an increased resistance to ischaemia reperfusion. Left ventricular function was measured in isolated perfused rat hearts before, during and after exposure to 45 min global normothermic ischaemia. Control hearts received Krebs throughout, whilst in treated hearts 0.5 mM L-cysteine was added to the perfusate 10 min before ischaemia, and was then present throughout ischaemia and for the first 10 min of reperfusion. Reperfusion injury was assessed from the appearance of lactate dehydrogenase (LDH) in the effluent. In two separate groups of control and treated hearts, ATP and glutathione (GSH) contents were measured at the beginning and end of ischaemia. Hearts treated with 0.5 mM L-cysteine showed a significantly higher recovery of rate pressure product (16,256+/- 1288 mmHg bpm vs. 10,324+/- 2102 mmHg bpm, p < 0.05) and a significantly lower release of LDH (0.54+/- 0.16 IU/g wet weight vs. 1.44+/- 0.31 IU/g wet weight, p < 0.05) compared to controls. Also, the L-cysteine treated group showed significantly better preservation of ATP and GSH during ischaemia in comparison to control. These results suggest that the mechanisms underlying the cardioprotective effects of 0.5 mM L-cysteine may include: increased anaerobic energy production either directly or through reduced degradation of adenine nucleotides; direct scavenging of free radicals; and/or improved antioxidant capacity through glutathione preservation.

DietaryL-Cysteine Improves the Antioxidative Potential and Lipid Metabolism in Rats Fed a Normal Diet

“…Those effects of L-cysteine might have been due to direct scavenging by free radicals or to an improved antioxidative status through the preservation of GSH. 20) In contrast, excessive dietary cysteine is known to cause oxidative stress. 32,33) It has even been reported that extreme doses of sulfur amino acid caused mortality in rats.…”

“…20) However, it is not yet fully understood whether L-cysteine supplementation has a positive effect on lipid metabolism together with the antioxidative system under normal conditions.…”

Inflammation, oxidative stress and postoperative atrial fibrillation in cardiac surgery

“…This drug is a precursor to the amino acid cysteine which is a rate-limiting factor in glutathione production. Inclusion of cysteine in the perfusate of perfused rat heart has been shown to confer significant cardioprotection and improved preservation of ATP and glutathione (Shackebaei, King, Shukla, & Suleiman, 2005).…”

Reduction of Ethanol‐Derived Acetaldehyde Induced Motivational Properties by l‐Cysteine

“…Because of the high reactivity of this thiol, cysteine is able to bind covalently and efficiently ACD by forming stable nontoxic 2-methyl-thiazolidine-4-carboxylic acid compound (Nagasawa et al, 1987;Salaspuro et al, 2006). Cysteine is efficacious to bind ACD derived from alcohol drinking to prevent the possible role of ACD in the pathogenesis of digestive tract cancer (Salaspuro, 2007;Salaspuro et al, 2002Salaspuro et al, , 2006, alcoholic cardiomyopathy, against the chronic toxicity of ACD (Sprince et al, 1974) and also for its antioxidant properties (Shackebaei et al, 2005). Moreover, N-acetyl cysteine, an analogue of the dietary amino acid cysteine attenuates EtOH-induced increased blood pressure and adverse renal vascular changes (Vasdev et al, 1995).…”