Urinary and Plasma Homocysteine and Cysteine Levels during Prolonged Oral N-Acetylcysteine Therapy

Ventura, Paolo; Panini, Rossana; Abbati, G.; Marchetti, G

doi:10.1159/000069535

Cited by 34 publications

(35 citation statements)

References 34 publications

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“…Thus, our results suggest that both sulfhydryl group and carboxyl group are required for eliciting the hypohomocysteinemic effect of cysteine. On the other hand, the fact that NAC had a hypohomocysteinemic effect (15)(16)(17)(18)(19)(20)(21)(22)(23) suggests that an amino group is not required for the effect of cysteine, although it cannot be ignored that NAC is easily hydrolyzed to cysteine and acetate.…”

Section: Discussionmentioning

confidence: 99%

Hypohomocysteinemic Effect of Cysteine Is Associated with Increased Plasma Cysteine Concentration in Rats Fed Diets Low in Protein and Methionine Levels

Kawakami

Ohuchi

Morita

et al. 2009

J Nutr Sci Vitaminol

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Summary Rats were fed diets with and without 0.5% L -cysteine supplement for 14 d or shorter periods to clarify the mechanism by which dietary cysteine elicits its hypohomocysteinemic effect. Cysteine supplementation significantly decreased plasma homocysteine concentration with an increase in plasma cysteine concentration in rats fed 10% casein diet (10C) or 15% soybean protein diet (15S) but not in rats fed 25% casein diet (25C) or 25% soybean protein diet. Cysteine supplementation also significantly suppressed hyperhomocysteinemia induced by choline-deprived 10C with an increase in plasma cysteine concentration but not that induced by 25C ϩ 0.65% methionine or 25C ϩ 0.4% guanidinoacetic acid. Hepatic S -adenosylmethionine (SAM) and homocysteine concentrations were significantly decreased by cysteine supplementation of 15S. These decreases in plasma homocysteine concentration and hepatic SAM and homocysteine concentrations due to cysteine supplementation disappeared when 15S was fortified with 0.3% methionine. The plasma homocysteine concentration significantly decreased with an increase in plasma cysteine concentration only 1 d after diet change from 15S to cysteine-supplemented 15S, while hepatic cystathionine ␤ -synthase and betaine-homocysteine S -methyltransferase activities were not altered. Unlike cysteine, cysteic acid and 2-mercaptoethylamine did not decrease plasma homocysteine concentration. These results indicate that cysteine markedly decreases plasma homocysteine concentration only when added to diets low in both protein and methionine levels and suggest that increased plasma cysteine concentration and decreased flow of methionine toward homocysteine formation, but not alteration of homocysteine-metabolizing enzyme activities, are associated with the hypohomocysteinemic effect of cysteine. Key Words hypohomocysteinemic effect, cysteine, homocysteine, low protein diet, low methionine diet Homocysteine is an intermediate in the metabolism of methionine (Fig. 1) ( 1 ), but a number of studies have suggested that an elevated plasma homocysteine concentration is an independent risk factor for cardiovascular disease ( 2 -4 ). It is thought that elevated plasma homocysteine concentrations cause arterial damage by several mechanisms, e.g., endothelial cell injury, platelet activation, and increased oxidizability of low-density lipoproteins ( 4 ). In humans, the normal range of plasma homocysteine concentration is 5 to 15 M , and a 5-M increase in the concentration of this amino acid is associated with a 60-80% increased risk of coronary heart disease ( 3 ). The plasma homocysteine concentration is affected by various factors, such as nutritional, physiological, hormonal, pharmacological, lifestyle, disease, and genetic factors ( 2 -4 ). Of these factors, genetic and nutritional factors are thought to have a greater influence on plasma homocysteine concentration. Many studies have been conducted in humans to investigate the effect of dietary treatments on plasma homocysteine concentration. However, studie...

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Section: Discussionmentioning

confidence: 99%

Hypohomocysteinemic Effect of Cysteine Is Associated with Increased Plasma Cysteine Concentration in Rats Fed Diets Low in Protein and Methionine Levels

Kawakami

Ohuchi

Morita

et al. 2009

J Nutr Sci Vitaminol

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“…[7,8] Intravenous NAC administration can reduce plasma tHcy by increasing the excretion of urinary thiol and urinary homocysteine and cysteine as disulfide forms. [26,27] Our results show that plasma tHcy was decreased after normal saline hydration post coronary angiography, with or without NAC; however, the combination of the two produces greater decreases.…”

Section: Discussionmentioning

confidence: 64%

IntravenousN-acetylcysteine with Saline Hydration Improves Renal Function and Ameliorates Plasma Total Homocysteine in Patients Undergoing Cardiac Angiography

et al. 2008

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Proinflammatory cytokines and hyperhomocysteinemia are associated with clinically relevant restenosis in coronary artery disease. N-acetylcysteine (NAC) can decrease proinflammatory cytokines and plasma homocystine as well as reduce contrastinduced nephropathy. The aim of this study, therefore, was to compare normal saline hydration with and without intravenous NAC in terms of changes in renal function, proinflammatory cytokines, inflammatory markers, and plasma total homocysteine during coronary angiography. Forty-six patients who underwent coronary angiography and/or stent implantation for unstable angina were enrolled and assigned to NAC or NS treatment groups based on normal saline hydration with or without intravenous NAC, respectively. The NS group had lower serum creatinine (Cre: p = 0.02) and plasma total homocysteine (tHcy; p < 0.001) and increased glomerular filtration rate (GFR; p = 0.003) after angiography. In the NAC group, the serum blood urea nitrogen (BUN; p = 0.001), Cre (p < 0.001), and plasma tHcy (p < 0.001) were lower, and the GFR (P = 0.013) was increased after angiography. There were no statistically significant differences in serum high-sensitivity C reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), or interleukin-10 (IL-10) before and after angiography in the NS and NAC groups. Intergroup comparison revealed that plasma tHcy level was lower for the NAC-treated patients (p = 0.002), with lower plasma tHcy level before and after treatment in this group (p < 0.001). Normal saline hydration can improve renal function and decrease plasma tHcy after coronary angiography with or without NAC; however, the combination of the two decreases plasma tHcy more than normal saline hydration alone.

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“…It has been shown that continued oral or i.v. treatment with N-acetylcysteine reduces plasma homocysteine levels, [22][23][24][25][26] which may have normalized elevated homocysteine levels in this patient. Furthermore, it may be that plasma homocysteine correlates only poorly with homocysteine levels at the site of action, that is, the mucosal cells in the lungs.…”

Section: Discussionmentioning

confidence: 77%

‘Flooding’ of the lungs and severe dyspnea in a patient with bronchoalveolar carcinoma

Keizer

Beijnen

Baas

2010

J Oncol Pharm Pract

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In this case report, we describe a patient with bronchoalveolar carcinoma that experienced severe bronchorrhea and dyspnea after inhalation of N-acetylcysteine. The adverse reactions occurred both after oral and nebulized administration of N-acetylcysteine, resulting in severe dyspnea and the feeling of 'drowning'. Bronchorrhea has previously been reported as an uncommon but serious complication of bronchoalveolar carcinoma. We strongly suspect the administration of N-acetylcysteine to be implicated, as the complications occurred immediately after administration of this drug. As the patient suffered from hyperhomocysteinemia, we speculate that an additive or synergistic interaction with homocysteine may have been involved as well.

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Urinary and Plasma Homocysteine and Cysteine Levels during Prolonged Oral N-Acetylcysteine Therapy

Cited by 34 publications

References 34 publications

Hypohomocysteinemic Effect of Cysteine Is Associated with Increased Plasma Cysteine Concentration in Rats Fed Diets Low in Protein and Methionine Levels

Hypohomocysteinemic Effect of Cysteine Is Associated with Increased Plasma Cysteine Concentration in Rats Fed Diets Low in Protein and Methionine Levels

IntravenousN-acetylcysteine with Saline Hydration Improves Renal Function and Ameliorates Plasma Total Homocysteine in Patients Undergoing Cardiac Angiography

‘Flooding’ of the lungs and severe dyspnea in a patient with bronchoalveolar carcinoma

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