SHORT REPORT
Amide Form of N-acetylcysteine Improves Outcomes in Experimental TBI
By Carrie Decker, ND
Founder and Medical Director, Blessed Thistle, Madison, WI
Dr. Decker reports no financial relationships relevant to this field of study.
- The amide form of N-acetylcysteine was shown to improve cognitive function, lower oxidative stress markers, and spare cortical tissue after traumatic brain injury (TBI) when given by intraperitoneal injection to rats at a dose of 150 mg/kg at time intervals ranging from 5 minutes through 24 hours post injury.
Mitochondrial oxidative stress and damage is connected to neuronal cell death and behavioral outcomes after TBI. Antioxidant treatment with the amide form of N-acetylcsyteine, which has central nervous system (CNS) bioavailability, was shown to improve markers of damage and cognitive function in rats when provided by intraperitoneal injection post experimental TBI.
Pandya JD, et al. N-acetylcysteine amide confers neuroprotection, improves bioenergetics and behavioral outcome following TBI. Exp Neurol 2014;257:106-113.
Traumatic brain injury (TBI) has been shown to lead to both rapid and prolonged mitochondrial disruption that overwhelms antioxidant systems. N-acetylcysteine (NAC), an antioxidant that is a precursor to glutathione (GSH), has been shown to improve mitochondrial function by increasing GSH levels after TBI. Increased cellular and mitochondrial permeability with a lipid soluble and neutrally charged amide form of NAC (NACA) improves CNS bioavailability of the molecule and may offer improved benefits.
A rat study, with experimenters blinded to treatments, assessed markers of cognitive function, cortical tissue, oxidative stress, mitochondrial respiration, and GSH levels in animals subjected to experimental TBI that were subsequently given intraperitoneal injections of NACA, NAC, or placebo vehicle. Comparisons with the non-amide form of NAC were only made in assessment of the cortical tissue sparing and cognitive function. To assess cortical tissue sparing, cognitive function, and oxidative stress, intraperitoneal injections of a NACA (or NAC) bolus of 150 mg/kg in a vehicle solution were provided at 30 minutes post-injury. To assess mitochondrial respiration and GSH content, intraperitoneal injections of a NACA bolus containing 150 mg/kg in a vehicle solution were provided at 5 minutes and 6-hour intervals up to 24 hours post-injury. All treatments were compared to treatment with the vehicle solution.
NACA was shown to significantly improve cognitive function (water maze learning ability) between 11 and 14 days post-TBI and treatment compared to both NAC and vehicle. Cortical tissue, evaluated at 15 days, was significantly spared with NACA treatment compared to treatments with both vehicle and NAC. Treatment with NAC was not observed to have any effect on cortical tissue or cognitive function. Oxidative stress, measured by lipid peroxidation, in rats treated with NACA was significantly decreased at 7 days post-TBI. Finally, mitochondrial respiration and total and reduced GSH content were significantly improved with NACA treatment at 25 hours post-injury with no significant difference from that of uninjured (untreated) animals. In contrast, rats treated with only the vehicle solution experienced significant decreases in each of these measures. These dosages are comparable to that utilized for acetaminophen toxicity in the United Kingdom, for which the treatment is intravenous NAC at a dosage of 150 mg/kg in the first 15-60 minutes, followed by lower doses through the initial 20-hour period. NACA (the amide form of NAC) is a relatively new formulation (2000s) of NAC, and is not the same as what is traditionally used in practice.
