PMID- 27901381 OWN - NLM STAT- MEDLINE DCOM- 20170502 LR - 20211204 IS - 1205-7541 (Electronic) IS - 0008-4212 (Linking) VI - 95 IP - 1 DP - 2017 Jan TI - Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia. PG - 32-42 LID - 10.1139/cjpp-2016-0147 [doi] AB - This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD. FAU - Hemanth Kumar, Boyina AU - Hemanth Kumar B AD - a Department of Pharmacology, Anurag Group of Institutions (Formerly Lalitha College of Pharmacy), Hyderabad, Telangana, India. AD - b Center for Pharmaceutical Sciences and Research and Development Cell, Jawaharlal Nehru Technological University, Hyderabad, Telangana, India. FAU - Arun Reddy, Ravula AU - Arun Reddy R AD - a Department of Pharmacology, Anurag Group of Institutions (Formerly Lalitha College of Pharmacy), Hyderabad, Telangana, India. AD - c Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ 08084, USA. FAU - Mahesh Kumar, Jerald AU - Mahesh Kumar J AD - d Animal House Facility, CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, Telangana 500007, India. FAU - Dinesh Kumar, B AU - Dinesh Kumar B AD - e National Institute of Nutrition (ICMR), Food & Drug Toxicology Research Centre (FDTRC), Hyderabad, Telangana 500007, India. FAU - Diwan, Prakash V AU - Diwan PV AD - a Department of Pharmacology, Anurag Group of Institutions (Formerly Lalitha College of Pharmacy), Hyderabad, Telangana, India. AD - f Maratha Mandal Central Research Laboratory, Belagavi-590010, Karnataka, India. LA - eng PT - Journal Article DEP - 20160811 PL - Canada TA - Can J Physiol Pharmacol JT - Canadian journal of physiology and pharmacology JID - 0372712 RN - 0 (Flavonoids) RN - 0 (Flavonols) RN - 0 (Indans) RN - 0 (Nitrites) RN - 0 (Piperidines) RN - 0LVT1QZ0BA (Homocysteine) RN - 31C4KY9ESH (Nitric Oxide) RN - 8SSC91326P (Donepezil) RN - 97C5T2UQ7J (Cholesterol) RN - AE28F7PNPL (Methionine) RN - EC 1.11.1.6 (Catalase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 3.1.1.7 (Acetylcholinesterase) RN - GAN16C9B8O (Glutathione) RN - OO2ABO9578 (fisetin) SB - IM MH - Acetylcholinesterase/metabolism MH - Animals MH - Aorta/pathology MH - Brain/metabolism MH - Catalase/metabolism MH - Cholesterol/blood MH - Dementia, Vascular/blood/complications/*drug therapy/metabolism MH - Donepezil MH - Dose-Response Relationship, Drug MH - Endothelium, Vascular/*drug effects MH - Flavonoids/*pharmacology/*therapeutic use MH - Flavonols MH - Glutathione/metabolism MH - Homocysteine/blood MH - Hyperhomocysteinemia/chemically induced/complications/*drug therapy/metabolism MH - Indans/therapeutic use MH - Lipid Peroxidation/drug effects MH - Male MH - Maze Learning MH - Methionine/adverse effects MH - Necrosis/drug therapy/pathology MH - Nitric Oxide/metabolism MH - Nitrites/blood MH - Piperidines/therapeutic use MH - Rats MH - Superoxide Dismutase/metabolism OTO - NOTNLM OT - Morris water maze OT - acetylcholinesterase OT - acetylcholinesterase OT - foyers necrotiques OT - l-NAME OT - l-methionine OT - l-methionine OT - labyrinthe aquatique de Morris OT - necrotic foci EDAT- 2016/12/03 06:00 MHDA- 2017/05/04 06:00 CRDT- 2016/12/01 06:00 PHST- 2016/12/03 06:00 [pubmed] PHST- 2017/05/04 06:00 [medline] PHST- 2016/12/01 06:00 [entrez] AID - 10.1139/cjpp-2016-0147 [doi] PST - ppublish SO - Can J Physiol Pharmacol. 2017 Jan;95(1):32-42. doi: 10.1139/cjpp-2016-0147. Epub 2016 Aug 11.