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.
Kumar
Alok
A
Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India.
Babu
G Nagesh
GN
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005434:Flow Cytometry; D018698:Glutamic Acid / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007737:Kynurenine / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D007737:Kynurenine; D018698:Glutamic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione