title: Reversal of neurobehavioral and neurochemical alterations in STZ-induced diabetic rats by FeTMPyP, a peroxynitrite decomposition catalyst and 1,5-Isoquinolinediol a poly(ADP-ribose) polymerase inhibitor.
abstract: OBJECTIVE
  In this study, we have evaluated the involvement of nitrosative stress and poly-ADP ribosyl polymerase (PARP) in diabetes induced neurobehavioral and neurochemical changes using pharmacological agents peroxynitrite decomposition catalyst (FeTMPyP) and a PARP inhibitor (1,5-Isoquinolinediol) in diabetic brains.
  
  
  METHODS
  The extent of neurobehavioral changes was assessed by functional observation battery, motor coordination activity (rota rod performance) and passive avoidance test. Neurochemical changes were assessed by measuring nicotinamide adenine dinucleotide (NAD), malondialdehyde, acetylcholinesterase, neurotransmitters (GABA and glutamate) levels in the hippocampus. GABA and glutamate were measured by high-performance liquid chromatography with electrochemical detection method.
  
  
  RESULTS
  Two weeks' treatment with FeTMPyP (3 mg/kg, i.p.) and 1,5-Isoquinolinediol (3 mg/kg, i.p.) improved the cognitive deficits in diabetic rats as observed in passive avoidance test. Both the agents inhibited lipid peroxidation and improves the acetylcholinesterase level in the hippocampus. 1,5-Isoquinolinediol treatment also improves the NAD, neurotransmitter level in the hippocampus.
  
  
  CONCLUSIONS
  These results suggest that peroxynitrite decomposition catalyst and PARP inhibitor have beneficial effects in neurobehavioral alterations induced by diabetes. Improvement in neurobehavioral alteration may be attributed to reversal of neurotransmitter homeostasis deficits.
authors.forename: Ashok
authors.initials: A
authors.lastname: Jangra
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Datusalia
authors.forename: Shyam Sunder
authors.initials: SS
authors.lastname: Sharma
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D058851:GPI-Linked Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D009243:NAD / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: C492721:5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato-iron(III); D001786:Blood Glucose; D004791:Enzyme Inhibitors; D058851:GPI-Linked Proteins; D007004:Hypoglycemic Agents; D007546:Isoquinolines; D008665:Metalloporphyrins; D018377:Neurotransmitter Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D030421:Peroxynitrous Acid; C095653:1,5-dihydroxyisoquinoline; D013311:Streptozocin; D011065:Poly(ADP-ribose) Polymerases; D000110:Acetylcholinesterase; C548246:Ache protein, rat
keywords: 1,; 5-Isoquinolinediol,; Diabetes; FeTMPyP,; Nitrosative stress,; PARP,; Peroxynitrite,