N-acetylcysteine Exerts Protective Effects and Prevents Lung Redox Imbalance and Peroxynitrite Generation in Endotoxemic Rats

Luis   F.   Carbonell; Julian      Diaz; Isabel      Hernandez; Santiago      Cuevas; Fernando      Valero; Tomas      Quesada; Francisco      Fenoy; Miguel   G.   Salom

Abstract

The aim of this study was to determine in endotoxemic rats the effects of N-acetylcysteine on lung redox imbalance and plasma peroxynitrite generation. Eighty male Wistar rats were divided in two sets of five experimental groups. Six hours after vehicle (Control group: isotonic NaCl sterile solution ip; n=7), lipopolysaccharide (LPS group: 1 mg/Kg ip; n=8), N-acetylcysteine plus LPS (NAC+LPS group, n=8), NAC plus the nitric oxide synthesis inhibitor Nw- nitro-L-arginine methyl ester plus LPS (NAC+NAME+LPS group; n=8), or NAME plus LPS (NAME+LPS group; n=9), arterial blood and lung samples were taken from each animal under sodium pentobarbital anesthesia. In five additional groups treated as described above, in vivo plasma oxidation of dihydrorhodamine (DRH) 123 to rhodamine (RH)123 was measured as index of peroxynitrite formation. LPS treated rats presented increased plasma lactate, thrombocytopenia and both, decreased reduced thiols and increased lipid peroxidation in lung tissue. Moreover, LPS produced increments in plasma concentration of nitrites/nitrates and DRH 123 oxidation. Pretreatment with NAC prevented all these changes induced by LPS except the increment in plasma concentration of nitrites/nitrates. The protective effects seen in LPS rats pretreated with NAC were not observed in the NAC+NAME+LPS group. In conclusion, the results of this study show that in endotoxemia induced by LPS in rats, NAC produces protective effects on lung redox balance and prevents peroxynitrite anion generation.

Keywords: Reactive oxygen species, antioxidants, lipopolysaccharide, lipid peroxidation, critical illness, reduced sulfhydryl groups

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