Protective Effect of N-Acetyl-Cysteine (NAC) in Lipopolysaccharide (LPS)-Associated Inflammatory Response in Rat Neonates
Nizar Khatib, Zeev Weiner, Yuval Ginsberg, Nibal Awad, and Ron BelooseskyAbstract
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.
Rambam Maimonides Med J 2017;8(2):e0026