Carnosine is a natural endogenous
dipeptide widely distributed in mammalian tissues, existing at particularly high concentrations in the muscles and brain and possesses well-characterized
antioxidant and anti-inflammatory activities. In an in vitro model of macrophage activation, induced by
lipopolysaccharide +
interferon-gamma (LPS + IFN-γ), we here report the ability of
carnosine to modulate
pro-oxidant and pro-inflammatory activities of macrophages, representing the primary cell type that is activated as a part of the immune response. An ample set of parameters aimed to evaluate cytotoxicity (MTT assay), energy metabolism (HPLC), gene expressions (high-throughput real-time PCR (qRT-PCR)),
protein expressions (western blot) and
nitric oxide production (qRT-PCR and HPLC), was used to assess the effects of
carnosine on activated macrophages challenged with a non cytotoxic LPS (100 ng/mL) + IFN-γ (600 U/mL) concentration. In our experimental model, main
carnosine beneficial effects were: (1) the modulation of
nitric oxide production and metabolism; (2) the amelioration of the macrophage energy state; (3) the decrease of the expressions of
pro-oxidant enzymes (Nox-2, Cox-2) and of the lipid peroxidation product
malondialdehyde; (4) the restoration and/or increase of the expressions of
antioxidant enzymes (Gpx1, SOD-2 and Cat); (5) the increase of the transforming growth factor-β1 (TGF-β1) and the down-regulation of the expressions of
interleukins 1β and 6 (IL-1β and IL-6) and 6) the increase of the expressions of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and
heme oxygenase-1 (HO-1). According to these results
carnosine is worth being tested in the treatment of diseases characterized by elevated levels of oxidative stress and
inflammation (
atherosclerosis,
cancer, depression,
metabolic syndrome, and
neurodegenerative diseases).