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NAC protected cartilage cells through glutathione and limited damage in rat knees

N-acetylcysteineLabAnimal2010

This 2010 study in rabbit cartilage cells and rats found that N-acetylcysteine (NAC), a building block for glutathione, protected cartilage cells from death caused by nitric oxide. The protection disappeared when glutathione production was blocked. Injected into the knees of rats with induced osteoarthritis, NAC reduced cartilage damage.

Evidence typeLab and Animal
Who or what was studiedCartilage cells from rabbit joints in the lab, and rats with experimentally induced osteoarthritis (numbers not given in the abstract)
Dose and durationCells: NAC at 0 to 2 mM, with sodium nitroprusside at 0.75 mM to trigger cell death. Rats: NAC injected into the joint (dose and duration not stated in the abstract)

What they did

Researchers grew cartilage cells from rabbit joints and treated them with NAC at concentrations up to 2 mM. They then exposed the cells to sodium nitroprusside, a chemical that releases nitric oxide, to trigger apoptosis, a programmed form of cell death. They measured cell survival, reactive oxygen species, glutathione, and two proteins in the cell-death pathway, p53 and caspase-3.

To test whether glutathione was doing the work, they added buthionine sulfoximine, a drug that blocks glutathione production. Finally, they injected NAC into the knee joints of rats with experimentally induced osteoarthritis and examined the cartilage.

What they found

NAC prevented nitric oxide-induced cell death, the build-up of reactive oxygen species, the rise in p53 and the activation of caspase-3. Blocking glutathione production significantly reduced NAC's protection, which points to glutathione as the route by which NAC worked.

In the rats, NAC injected into the joint significantly reduced cartilage destruction and cartilage cell death.

What it can't tell us

The cells came from rabbits and the joint test was in rats; neither is a person. NAC was injected straight into the joint, not swallowed, so the study cannot say whether NAC taken by mouth would reach cartilage in the same way. The abstract does not give the rat dose, treatment length or number of animals.

Why it matters

This study does more than show NAC helps cartilage cells. By blocking glutathione production and watching the protection disappear, it showed the benefit ran through glutathione made by the cartilage cells themselves. That is direct evidence, in cells, that supplying a glutathione building block works by helping the cell make its own.

The paper

  1. Nakagawa S, Arai Y, Mazda O et al. N-acetylcysteine prevents nitric oxide-induced chondrocyte apoptosis and cartilage degeneration in an experimental model of osteoarthritis. J Orthop Res 2010.
Last reviewed Every study cited here is indexed on PubMed. How we read the evidence