Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 3/1/2007
Publication Date: 4/28/2007
Citation: Baumgardner, J., Shankar, K., Badger, T.M., Ronis, M.J. 2007. Effects of N-acetylcysteine on non-alcoholic steatohepatitis (NASH) in rats fed via total enteral nutrition [abstract]. The FASEB Journal. 21(5):A725.
Interpretive Summary: Non-alcoholic steatohepatitis (NASH) is a common complication of childhood obesity. There is no therapy for NASH that has been proven to be clearly effective. We have successfully developed a new rat model to study NASH. The rats are essentially overfed a high fat diet using total enteral nutrition, the same procedures used clinically to feed ill children in the hospital. In addition, using this model, we have found that N-acetylcysteine (NAC), an antioxidant commonly used as a food preservative, may be an effective treatment for NASH. These are important findings, and this model will be used in future studies to learn more about how to prevent and treat childhood obesity and complication from obesity.
Technical Abstract: A "two-hit" model for NASH exists in which development of steatosis constitutes the "first hit" and sensitizes the liver to potential "second hits", resulting in NASH. Oxidative stress is possibly a central mechanism of hepatocellular injury in NASH and is a candidate for the "second hit" since it can explain the histological features of the disease. N-acetylcysteine (NAC), an antioxidant, has been suggested to be a possible dietary therapy for NASH clinically. We examined the effects of NAC in a Total Enteral Nutrition (TEN) model of NASH developed in our lab. In this NASH model, we feed male Sprague-Dawley rats (175 g) intragastrically by TEN for 21-65 days, a standard, 187 kcal/kg3/4/d diet containing 5% corn oil (CO) or an overfed, 220 kcal/kg3/4/d diet containing 5% or 70% CO. As indicated by hepatic pathology, elevated ALT levels, oxidative stress and increased TNF-', the overfed 70% CO group is identical to clinical NASH. The addition of NAC (2 g/kg/d) to the 70% CO diet provided partial protection against ALT release (p'0.05); however, ALT values were still significantly elevated relative to 5% CO groups (p'0.05). This was accompanied by a significant decrease in oxidative stress as measured by TBARS (p'0.05). In conclusion, using NAC in combination with the TEN model for NASH, we have demonstrated that NAC could be a beneficial therapy for NASH; however, further studies are required to investigate the clinical implications of these findings.