d-Arginine action against neurotoxicity induced by glucocorticoids in the brain

Glucocorticoids (GC) are necessary for normal life but elevated levels of GC have been implicated in the development of several neurological diseases and psychiatric disorders. Nowadays, it is well known that high levels of GC in the central nervous system (CNS) generate an increase in the production of reactive oxygen species (ROS), derived mainly from the nitric oxide (NO) pathway. Accordingly, there is an increase of l-arginine (l-Arg.) availability. This report reviews the evidence that d-arginine (d-Arg.) induces normalization of l-Arg. resulting in protection against GC neurotoxic actions in the hippocampus. It is important to highlight that this D-amino acid does not interfere with the expected peripheral effects of GC such as suppression of the hypothalamic–pituitary–adrenal axis (HPA axis) and the immune response, commonly used in clinical practice.

Research highlights► Glucocorticoids neurotoxic actions increase l-arginine availability. ► d-Arginine normalizes l-arginine concentration until physiological values. ► D-Arginine counteracts glucocorticoids neurotoxic actions. ► d-Arginine has not effects with physiological concentrations of l-arginine. ► d-Arginine does not modify glucocorticoids peripheral parameters.