title: Nephroprotective effects of TVP1022, a non-MAO inhibitor S-isomer of rasagiline, in an experimental model of diabetic renal ischemic injury.
abstract: Ischemic acute kidney injury (iAKI) in diabetes mellitus is associated with a rapid deterioration of kidney function, more than in nondiabetic subjects. TVP1022, a non-MAO inhibitor S-isomer of rasagiline, possesses antioxidative and antiapoptotic activities. The current study examines the effects of TVP1022 and tempol on iAKI in diabetic rats. Diabetes was induced by streptozotocin. iAKI was induced by clamping the left renal artery for 30 min in both diabetic and nondiabetic rats. The right intact kidney served as a control. Forty-eight hours following ischemia, urinary flow (V), sodium excretion (UNaV), and glomerular filtration rate (GFR) in both ischemic and nonischemic kidneys were determined. The nephroprotective effects of tempol and TVP1022 were examined in these rats. Hematoxylin and eosin staining, 4-hydroxynonenal (4-HNE) immunofluorescence, and nitrotyrosine immunohistochemistry were performed on renal tissues of the various experimental groups. Compared with normoglycemic rats, iAKI in diabetic animals caused more profound reductions in V, UNaV, and GFR. Tempol and TVP1022 treatment increased GFR two- and four-fold in diabetic ischemic kidney, respectively. Besides hemodynamic perturbations, iAKI markedly increased renal immunoreactive 4-HNE and nitrotyrosine staining in both diabetic and nondiabetic rats. Moreover, iAKI increased medullary necrosis, congestion, and casts. Noteworthy, these increases were to a larger extent in ischemic diabetic kidneys. TVP1022, and to a lesser extent tempol, decreased nitrotyrosine and 4-HNE immunoreactivities and necrosis and cast formation in the renal medulla. TVP1022 treatment improves renal dysfunction and histological changes in an iAKI diabetic model and suggests a role for TVP1022 therapy in kidney injury.
authors.affiliation: Dept. of Physiology and Biophysics. Faculty of Medicine, Technion, IIT, PO Box 9649, Haifa 31096, Israel. abassi@tx.technion.ac.il.
authors.forename: Niroz
authors.initials: N
authors.lastname: Abu-Saleh
authors.forename: Hoda
authors.initials: H
authors.lastname: Awad
authors.forename: Mogher
authors.initials: M
authors.lastname: Khamaisi
authors.forename: Zaher
authors.initials: Z
authors.lastname: Armaly
authors.forename: Tony
authors.initials: T
authors.lastname: Karram
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Heyman
authors.forename: Aviva
authors.initials: A
authors.lastname: Kaballa
authors.forename: Takaharu
authors.initials: T
authors.lastname: Ichimura
authors.forename: James
authors.initials: J
authors.lastname: Holman
authors.forename: Zaid
authors.initials: Z
authors.lastname: Abassi
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D007189:Indans / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D013113:Spin Labels; D013312:Stress, Physiological
chemical_list: D003497:Cyclic N-Oxides; D007189:Indans; D018696:Neuroprotective Agents; D013113:Spin Labels; C031967:rasagiline; C001803:tempol
keywords: acute kidney injury; diabetes mellitus; oxidative stress; rasagiline