L-Arginine induces antioxidant response to prevent oxidative stress via stimulation of glutathione synthesis and activation of Nrf2 pathway

Arginine is a conditionally essential amino acid. To elucidate the influence of L-arginine on the activation of endogenous antioxidant defence, male Wistar rats were orally administered daily with L-arginine at different levels of 25, 50, 100 mg/100 g body weight. After 7 and 14 days feeding, the antioxidative capacities and glutathione (GSH) contents in the plasma and in the liver were uniformly enhanced with the increasing consumption of L-arginine, whereas the oxidative stress was effectively suppressed by L-arginine treatment. After 14 days feeding, the mRNA levels and protein expressions of Keap1 and Cul3 were gradually reduced by increasing L-arginine intake, resulting that the nuclear factor Nrf2 was activated. Upon activation of Nrf2, the expressions of antioxidant responsive element (ARE)-dependent genes and proteins (GCLC, GCLM, GS, GR, GST, GPx, CAT, SOD, NQO1, HO-1) were up-regulated by L-arginine feeding, indicating an upward trend in antioxidant capacity uniformly with the increasing consumption of L-arginine. The present study demonstrates that the supplementation of L-arginine stimulates GSH synthesis and activates Nrf2 pathway, leading to the up-regulation of ARE-driven antioxidant expressions via Nrf2-Keap1 pathway. Results suggest the availability of L-arginine is a critical factor to suppress oxidative stress and induce an endogenous antioxidant response.