Curcumin Induces Glutathione Biosynthesis and Inhibits NF-κB Activation and Interleukin-8 Release in Alveolar Epithelial Cells: Mechanism of Free Radical Scavenging Activity

Abstract

Oxidants and tumor necrosis factor-alpha (TNF-alpha) activate transcription factors such as nuclear factor-kappaB (NF-kappaB), which is involved in the transcription of proinflammatory mediators, including interleukin-8 (IL-8). Curcumin (diferuloylmethane) is a naturally occurring flavonoid present in the spice turmeric, which has a long traditional use as a chemotherapeutic agent for many diseases. We hypothesize that curcumin may possess both antioxidant and antiinflammatory properties by increasing the glutathione levels and inhibiting oxidant- and cytokine-induced NF-kappaB activation and IL-8 release from cultured alveolar epithelial cells (A549). Treatment of A549 cells with hydrogen peroxide (H2O2; 100 microM) and TNF-alpha (10 ng/ml) significantly increased NF-kappaB and activator protein-1 (AP-1) activation, as well as IL-8 release. Curcumin inhibited both H2O2- and TNF-alpha-mediated activation of NF-kappaB and AP-1, and IL-8 release. Furthermore, an increased level of GSH and glutamylcysteine ligase catalytic subunit mRNA expression was observed in curcumin-treated cells as compared with untreated cells. Curcumin interacted directly with superoxide anion (O2*-) and hydroxyl radical (*OH) as shown by electron paramagnetic resonance, quenching the interaction of the radicals with the spin trap, Tempone-H. This suggests that curcumin has multiple properties: as an oxygen radical scavenger, antioxidant through modulation of glutathione levels, and antiinflammatory agent through inhibition of IL-8 release in lung cells.

Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane)

“…Curcumin has been shown to induce GSH biosynthesis [5]. It is unlikely that curcumin reacts with GSH directly under our conditions, as Oetari et al, 1996 showed that GSH prevents the instability of curcumin in phosphate buffer at pH 7.4 [53].…”

“…Extensive research within the last half-a-decade has confirmed that curcumin mediates anti-inflammatory effects through the downregulation of transcription factor nuclear factor-κB (NF-κB) [1,2] tumor necrosis factor (TNF) [3], interleukin-6 (IL-6) [4], interleukin-8 (IL-8) [5], adhesion molecules [6], inducible nitric oxide synthase (iNOS) [7], matrix metalloproteinase-9 (MMP-9) [8], cyclooxygenase-2 (COX-2) [9], and 5-lipoxygenase (5-LOX) [10]. In fact, curcumin has been shown to bind to an active site in 5-LOX, and the two together have been cocrystallized [11].…”

The protective effect of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues

“…These results show that acrylamide causes a signifi cant decrease in antioxidant parameters. Acrylamide especially decreases the GSH and GST activity levels of cells, spoils the oxidant/antioxidant balance against the oxidants and thus leads to oxidative damage in cells (1,14,(50)(51)(52)(55)(56)(57)(58).…”

Prevention of Nephropathy by Some Natural Sources of Antioxidants

“…Biswas et al [34] found that curcumin has antiinflammatory and antioxidant properties with a potent ability to inhibit reactive oxygen species formation. Azab et al [5] reported that in gentamicin treated Guinea pigs, there were physiological and structural changes in the kidney.…”