NACET - A More Bioavailable & Powerful F ...

NACET - A More Bioavailable & Powerful Form of NAC?

Dec 14, 2021

Hearing damage, it has been shown, occurs due to oxidative stress within the inner ear, or cochlea. NAC acts as an antioxidant to help quell this stress and the associated free radicals. In studies NAC has been shown to slow age-related hearing loss in mice and decrease the noise-induced permanent hearing loss in rats. Chinchillas pretreated with NAC showed a significant reduction in cochlear hair cell loss when exposed to noise, and in rabbits it protected against acoustic trauma-induced hearing damage. Human studies have shown it to be effective treatment for sudden deafness and military acoustic ear trauma in the short- and long-term. However, when scientists exposed chinchillas to long duration, broadband noise exposure, they found that NAC has its limits, as it wasn’t able to help recover hearing in chinchillas after such severe noise stress.

In addition to hearing, NAC helps with oxidative stress on the eyes, as a recent study review confirms that it has been researched to help with corneal wounds, chemical injuries, keratitis, dry eye disease and meibomian gland dysfunction; and showing potential in diabetic eye disease, retinitis pigmentosa, and macular degeneration.

Although NAC is useful for improving hearing and eyesight, its abilities are a little limited. Scientists from Italy expressed this when they noted that “Recent large clinical trials failed to confirm the supposed beneficial effects of N-acetylcysteine (NAC) in preventing oxidative stress-related diseases” probably “due to its low bioavailability.” They proposed “esterification of the carboxyl group of NAC to produce N-acetylcysteine ethyl ester (NACET).” This new compound “rapidly enters the cells where it is trapped being transformed into NAC and cysteine. After oral treatment, NACET (but not NAC) was able to increase significantly the glutathione content of most tissues examined, brain included, and to protect from paracetamol (acetaminophen/Tylenol) intoxication in the rat.”

In a 2018 study, it was noted that “NACET, with high oral bioavailability, is a strong antioxidant and abundant precursor of GSH, unlike its free acid N-acetyl-L-cysteine (NAC).” More 2018 research validated that it was the most efficient out of 4 molecules, NAC included, at increasing intracellular levels of GSH, cysteine, and γ-glutamylcysteine. And finally in 2021, another Italian study showed that “NACET, but not NAC, pretreatment” gives cells stress resistance and increases the GSH pool for natural antioxidant defense. They found that it increased GSH levels in rats’ eyes after oral administration, and “may represent a valid and more efficient alternative to NAC in therapeutic protocols in which NAC has already shown promising results.”

Source Links:

1)      N-acetylcysteine Treatment Reduces Age-related Hearing Loss and Memory Impairment in the Senescence-Accelerated Prone 8 (SAMP8) Mouse Model:

2)      N-acetylcysteine attenuates noise-induced permanent hearing loss in diabetic rats:

3)      Reduction of noise-induced hearing loss using L-NAC and salicylate in the chinchilla:

4)      Protective effects of N-acetylcysteine on noise-induced hearing loss in guinea pigs:

5)      Prevention of Acoustic Trauma-Induced Hearing Loss by N-acetylcysteine Administration in Rabbits:

6)      N-acetylcysteine as a single therapy for sudden deafness:

7)      Treatment of military acoustic accidents with N-Acetyl-L-cysteine (NAC):

8)      The effectiveness of N-acetyl-L-cysteine (L-NAC) in the prevention of severe noise-induced hearing loss:

9)      The role of topical N-acetylcysteine in ocular therapeutics:

10)   Efficacy of N-acetyl carnosine in the treatment of cataracts:

11)   N-Acetylcysteine ethyl ester (NACET): a novel lipophilic cell-permeable cysteine derivative with an unusual pharmacokinetic feature and remarkable antioxidant potential:

12)   N-acetylcysteine ethyl ester as GSH enhancer in human primary endothelial cells: A comparative study with other drugs (2018):

13)   S-Nitroso- N-acetyl-L-cysteine ethyl ester (SNACET) and N-acetyl-L-cysteine ethyl ester (NACET)-Cysteine-based drug candidates with unique pharmacological profiles for oral use as NO, H 2 S and GSH suppliers and as antioxidants: Results and overview (2018):

14)   Superior Properties of N-Acetylcysteine Ethyl Ester over N-Acetyl Cysteine to Prevent Retinal Pigment Epithelial Cells Oxidative Damage

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