Asymmetric dimethylarginine (ADMA), 4-OH-nonenal and Vitamin E levels in chronic schizophrenic patients.

Schizophrenia is a severe neurodegenerative brain disorder characterized by hallucinations, delusions, disorganized thoughts and cognitive disabilities. The disease affects 1% of the world population and is thought to have multiple etiologies (Akiibinu et al., 2012; Rich and Caldwell, 2015). Oxidative stress is believed to be an essential component in the schizophrenia pathophysiology (Ciobica et al., 2011). Nitric oxide (NO) is a free oxygen radical which carries out roles such as neuromodulator and neurotransmitter in peripheral and central nervous systems. It is considered that NO has a major role in the pathogenesis of schizophrenia and several neuropsychiatric disorders (Zincir et al., 2014). NO is known to have effects on the storage, uptake and/or release of neurotransmitters such as acetylcholine, dopamine, noradrenaline, GABA, glutamate, taurine and glycine in the central nervous system (CNS) (Bernstein et al., 2005). NO is produced by Nitric Oxide Synthase (NOS) (Zincir et al., 2014). NOS catalyzes the formation of nitric oxide from L-arginine (Jorgensen et al., 2015). Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NOS. ADMA and N-monomethyl-L-arginine (L-NMMA) are analogs of the NO precursor L-arginine and they act as endogenous inhibitors for all NOS isoforms. These endogenous inhibitors are synthesized by the methylation of residues of protein arginine in various proteins by arginine methyl transferase (PRMT) (Pope et al., 2007; Yildirim et al., 2006). ADMA and L-NMMA are converted to L-citrulline and methylamine by dimethylarginine dimethylaminohydrolase enzyme (DDAH). PRMT enzyme is involved in the formation of ADMA, while DDAH is involved in the degradation of ADMA