title: Pharmacological induction of hemeoxygenase-1 activity attenuates intracerebroventricular streptozotocin induced neurocognitive deficit and oxidative stress in rats.
abstract: Under conditions of oxidative stress associated with neurodegenerative disorders, alterations in hemeoxygenase-1 (HO-1) activity have been reported. In the present study we have investigated the role of HO-1 pathway in intracerebroventricular (ICV) streptozotocin (STZ) induced neurocognitive deficits and oxidative stress in rats. STZ was infused ICV bilaterally (3mg/Kg) on the alternate days in rats. Hemin was used as a pharmacological inducer of HO-1 activity and tin-protoporphyrin (SnPP) as HO-1 inhibitor. Hemin was administered with or without SnPP from day to 21 following 1st STZ infusion in rats. The cognitive functions were assessed by Morris water maze (MWM) and object recognition task (ORT) in rats. Biochemically, rat hippocampal and cortical brain homogenate was used to assess the levels of oxidative stress markers and acetylcholinesterase and HO-1 activity. Infusion of STZ caused significant elevation HO-1 activity on day 7 following 1st STZ infusion, however it was decreased on day 21, indicating its oxidative modification. Hemin caused significant elevation in HO-1 activity and attenuated STZ-induced oxidative stress. Moreover, hemin restored acetylcholinesterase activity and cognitive functions in STZ infused rats. Pre-administration of SnPP completely abrogated beneficial effects of hemin in STZ rats, indicating HO-1 dependency. The observed beneficial effects of hemin on spatial memory may be due to its ability to favorably modulate HO-1 pathway and antioxidant mechanisms.
authors.affiliation: Department of Pharmacology, I.S.F. College of Pharmacy, Moga, Punjab, India.
authors.forename: Manveen
authors.initials: M
authors.lastname: Bhardwaj
authors.affiliation: Department of Pharmacology, I.S.F. College of Pharmacy, Moga, Punjab, India. Electronic address: login2rd@gmail.com.
authors.forename: Rahul
authors.initials: R
authors.lastname: Deshmukh
authors.affiliation: Department of Pharmacology, I.S.F. College of Pharmacy, Moga, Punjab, India.
authors.forename: Madhu
authors.initials: M
authors.lastname: Kaundal
authors.affiliation: Department of Pharmacology, I.S.F. College of Pharmacy, Moga, Punjab, India.
authors.forename: B V
authors.initials: BV
authors.lastname: Krishna Reddy
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology; D057967:Infusions, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008665:Metalloporphyrins / Q000494:pharmacology / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011524:Protoporphyrins / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D013311:Streptozocin / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011524:Protoporphyrins; D013311:Streptozocin; D006427:Hemin; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1; D000110:Acetylcholinesterase
keywords: Alzheimer's disease; Cognitive dysfunction; Dementia; Hemeoxygenase-1; Neurodegenerative disorders; Oxidative stress