L-ARGININE DOWN-REGULATED TNF-ALPHA GENE IN LPS INDUCED INFLAMMATION IN EXPERIMENTAL RATS.

Mohamed A. Moustafa*, Doaa A. Ghareeb, Elsayed Elsayed Hafez, Bassiouny El-Gamal , Mohamed El-Sadanii

ABSTRACT

Lipopolysaccharide (LPS) induced the over- expression of a large amount of inflammatory mediators such as TNF-alpha and IFN-gamma which induced the transcription of inducible nitric oxide synthase (iNOS). L-Arginine modulates the action of NO and could be control the inflammation process. This study was conducted to elucidate the importance of L-Arginine as immunomodulator upon intraperitoneal injection of rats with potent inflammatory inducer, LPS and to deduce the exact mechanism by which L-arginine modulate or activate the immunity system either through induction of nitric oxide synthase (NOS) or arginase pathway. To evaluate these objectives, 5 groups, were intraperitoneally injected as follow; Control group), protection group: injected with 10 mg/kg L-Arginine for 7 days then once injected with 4mg/kg LPS, treatment group: injected with LPS followed by L-Arginine, Inhibition group: injected sequentially with LPS, L-Arginine and 10mg/kg NG nitro L-Arginyl methyl ester (L-NAME), and finally induction group injected with LPS only. Cytokines IL-6 and IL-1b levels were estimated by using ELISA while TNF alpha was estimated by qPCR. Furthermore, hepatic, renal functions and oxidative stress parameters were estimated colorimetric. Our results showed that, the level of total plasma nitrite was increased in both treatment and protection group and decreased in the inhibition group. Moreover, the level of pro-inflammatory cytokines (IL-1B, IL-6 and TNF alpha) were increased in the both induction and inhibition group and decreased in the treatment and protection groups. Altogether, L-Arginine plays an important role as an immunomodulator through NO-iNOS metabolic pathway.

Keywords: L-Arginine, Lipopolysaccharide, Pro-inflammatory cytokines, L-NAME, TNF-alpha, NO.