Protective Effect of N-Acetyl-Cysteine (NAC) in Lipopolysaccharide (LPS)-Associated Inflammatory Response in Rat Neonates.

OBJECTIVE

Increased inflammatory response may be associated with adverse clinical outcomes, especially in the neonatal period. The aims of this study were to determine whether N-acetyl-cysteine (NAC), an anti-inflammatory agent, attenuates the inflammatory response in young rats and to determine the most effective route of administration.

METHODS

Four groups of Sprague-Dawley rats (in each group four rats) were studied at 30 days of age. One hour following intraperitoneal (IP) injection of lipopolysaccharide 50 μg/kg, the rats were randomized to subcutaneous (SC), per os (PO), or intraperitoneal (IP) injection of NAC 300 mg/kg, or saline. The control group received saline injection (IP). Three hours following the N-acetyl-cysteine injection the rats were sacrificed, then serum tumor necrosis factor-α (TNF-α) and IL-6 levels were determined by ELISA.

RESULTS

Lipopolysaccharide significantly increased the neonatal serum IL-6 and TNF-α (2051.0±349 and 147.0±25.8 pg/mL, respectively; P<0.01) levels compared to 10 pg/mL in the controls. N-acetyl-cysteine administered one hour following lipopolysaccharide injection significantly attenuated the inflammatory response. Intraperitoneal administration of NAC decreased IL-6 and TNF-α concentration to 294.6 and 17.1 pg/mL, respectively, and was more effective than SC or PO administration.

CONCLUSIONS

N-acetyl-cysteine attenuated the inflammatory response in the neonatal rats, and IP was the most effective administration route.