In vivo neuroprotective effects of peripheral kynurenine on acute neurotoxicity induced by glutamate in rat cerebral cortex.

N-methyl-D-aspartate (NMDA) receptors play a crucial role in Glutamate (L-Glu) neurotoxicity. To evaluate the effects of astrocyte-derived tryptophan metabolite kynurenic acid (KYNA), on L-Glu neurotoxicity, adult male rats were pretreated with Kynurenine (KYN) which is a precursor of KYNA, at a dose of 30 mg or 300 mg/kg bw i.p., 2 h before stereotactic L-Glu bolus (1 micromole/1 microl) administration in cerebral cortex. Results showed that acute L-Glu increased reactive oxygen species, rate of lipid peroxidation, calcium, nitric oxide and neuroinflammatory markers viz. TNF-alpha, IFN-gamma levels and decreased key antioxidant parameters such as SOD, catalase, total glutathione and glutathione reductase along with mitochondrial membrane potential. While peripheral loading of 30 mg/kg dose of KYN had no protective effects on L-Glu induced neurotoxicity, 300 mg/kg dose prevented the above toxic effects following intracortical L-Glu. KYN apparently crossed blood brain barrier to elevate astrocytic-KYNA level, which seems to protect neurons through several interactive mechanisms.