Effectiveness of NAC at restoring depleted glutathione levels

[Guest guest]

Here's an animal study worth looking at re: the value of

supplementing with the glutathione precursor, N-acetyl-cysteine.

The abstract is included in full below, here's a quick summary.

They induced hypertension in rats with a specific regimen designed

for that purpose. In the 6th week, this regimen caused left

ventricular damage and dysfunction, which correlated with increases

in TNF-alpha and depletion of glutathione.

" NAC treatment, which replenished cardiac glutathione, had no effect

on hypertension but reduced LV [left ventricle] remodeling and

dysfunction, normalized serum TNF-alpha level, and limited

activation of matrix metalloproteinases -2 and -9 and collagen

deposition in LV tissues. "

Wasn't someone just asking about what was available to reduce MMP9?

This looks like one answer.

Here's the Pub Med abstract in full:

Circulation. 2004 Oct 5;110(14):2003-9. Epub 2004 Sep 27.

N-acetylcysteine treatment normalizes serum tumor necrosis factor-

alpha level and hinders the progression of cardiac injury in

hypertensive rats.

Bourraindeloup M, Adamy C, Candiani G, Cailleret M, Bourin MC,

Badoual T, Su JB, Adubeiro S, Roudot-Thoraval F, Dubois-Rande JL,

Hittinger L, Pecker F.

Federation de Cardiologie, Hopital Henri Mondor, Creteil, France.

BACKGROUND: Studies in isolated cardiomyocytes showed that

replenishment in cellular glutathione, achieved with the glutathione

precursor N-acetylcysteine (NAC), abrogated deleterious effects of

tumor necrosis factor-alpha (TNF-alpha).

METHODS AND RESULTS: We examined the ability of NAC to limit the

progression of cardiac injury in the rat model of hypertension,

induced by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine

methyl ester (L-NAME) (50 mg/kg per day SC) and high-salt diet (HS)

(8% NaCl). Four-week HS/L-NAME administration induced hypertension

(193+/-8 versus 122+/-4 mm Hg for low-salt diet [LS] group) and left

ventricular (LV) dysfunction, revealed by echocardiography and

characterized by decreased LV shortening fraction (38+/-2% versus

49+/-4% for LS group; P<0.05) and decreased LV posterior wall

thickening (49+/-3% versus 70+/-4% for LS group; P<0.05). LV

dysfunction worsened further after 6-week HS/L-NAME administration.

Importantly, increase in serum TNF-alpha level was strongly

correlated with shortening fraction decrease and cardiac glutathione

depletion.

NAC (75 mg/d) was given as a therapeutic treatment in a subgroup of

HS/L-NAME animals during weeks 5 and 6 of HS/L-NAME administration.

NAC treatment, which replenished cardiac glutathione, had no effect

on hypertension but reduced LV remodeling and dysfunction,

normalized serum TNF-alpha level, and limited activation of matrix

metalloproteinases -2 and -9 and collagen deposition in LV tissues.

CONCLUSIONS: These findings suggest that glutathione status

determines the adverse effects of TNF-alpha in cardiac failure and

that TNF-alpha antagonism may be achieved by glutathione

supplementation.

PMID: 15451797 [PubMed - indexed for MEDLINE]