title: Glycine aggravates ischemia reperfusion-induced acute kidney injury through N-Methyl-D-Aspartate receptor activation in rats.
abstract: The present study was designed to investigate the role of glycine in ischemia reperfusion-induced acute kidney injury (AKI) in rats. The AKI was induced in rats by occluding renal pedicles for 40 min followed by reperfusion for 24 h. The AKI was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, potassium, fractional excretion of sodium, and microproteinuria. The oxidative stress in renal tissues was assessed by quantification of myeloperoxidase activity, thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. Glycine (100, 200, and 400 mg/kg, i.p.) was administered to rats 30 min before subjecting to AKI. The glycinergic receptor blocker, strychnine (0.75 mg/kg i.p.), and glycine-binding site blocker at N-methyl-D-aspartate (NMDA) receptor, kynurenic acid (300 and 600 mg/kg i.p.), were used in the present study. The ischemia reperfusion induced AKI as witnessed by significant change in plasma, urinary, and tissue parameters employed in the present study. Glycine treatment increased ischemia reperfusion-induced AKI. The treatment with strychnine did not show any protection, whereas kynurenic acid ameliorated renal ischemia reperfusion-induced AKI. The results obtained in present study suggest that glycine increases ischemia reperfusion-induced renal damage through NMDA receptor agonism rather than strychnine-sensitive glycinergic receptors. Hence, it is concluded that glycine aggravates ischemia reperfusion-induced AKI. In addition, the activation of strychnine-insensitive glycine-binding site of NMDA receptors is responsible for its renal-damaging effect rather than strychnine-sensitive glycinergic receptors.
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, INDIA.
authors.forename: Shiyana
authors.initials: S
authors.lastname: Arora
authors.forename: Tajpreet
authors.initials: T
authors.lastname: Kaur
authors.forename: Anudeep
authors.initials: A
authors.lastname: Kaur
authors.forename: Amrit Pal
authors.initials: AP
authors.lastname: Singh
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001665:Binding Sites; D005998:Glycine / Q000008:administration & dosage*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007736:Kynurenic Acid / Q000008:administration & dosage; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013331:Strychnine / Q000008:administration & dosage
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D007736:Kynurenic Acid; D013331:Strychnine; D005998:Glycine
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