l-Arginine prevents 4-hydroxy-2-nonenal accumulation and depresses inflammation via inhibiting NF-κB activation.

4-Hydroxy-2-nonenal (HNE) is an inducer of inflammation. The aim of this study was to elicit the link between the inhibition of HNE accumulation and the depression of inflammation whether dependent onl-arginine availability in growing rats. Male Wistar rats were fed with different levels of l-arginine at 250, 500, and 1000 mg/kg body weight for 14 days. The control group was fed with commercial pellets. After 14 days of oral administration, l-arginine significantly reduced hepatic accumulation of HNE and depressed inflammation in rats as compared with the control group. Compared to the control group, the anti-inflammatory action of l-arginine is reflected by upregulation of hepatic interleukin-10 (IL-10) and the suppression of hepatic cyclooxygenase-2, tumor necrotic factor α, IL-1β, and IL-6 expressions in growing rats. With l-arginine administration, the activation of nuclear factor-κB (NF-κB) was efficaciously inhibited through the upregulation of inhibitory κBα, and the depression of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt). In conclusion, this study demonstrated that l-arginine could reduce hepatic HNE levels and depress inflammation in growing rats, revealing a link between the inhibition of HNE accumulation with the depression of inflammation, which was attributed to the availability of l-arginine. A significant finding of this study was that the anti-inflammatory mechanism exerted by l-arginine was to inhibit NF-κB activation via downregulating PI3K/Akt.