Hesperidin, a citrus flavonoid, protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats.
BACKGROUND
Hesperidin (HSP), a flavanoglycone found in citrus fruits, has antioxidant, anti-inflammatory and neuroprotective properties.


OBJECTIVE
This study evaluates the protective effect of HSP on l-methionine-induced hyperhomocysteinemia (HHcy) in rats.


METHODS
Male Wistar rats were randomly divided into seven groups as DMSO, l-methionine, HSP (25, 50 and 100 mg/kg), HSP-per se (100 mg/kg) and donepezil (0.1 mg/kg). HHcy was induced by oral administration of l-methionine (1.7 g/kg) for 32 days. From the 14thday of study HSP (25, 50 and 100 mg/kg) and donepezil was administered orally to l-methionine-treated rats. Cognitive impairment induced by HHcy was determined using the Morris water maze (MWM) and Y-maze on video tracking system (28th-32ndday). Different biomarkers of HHcy in serum and brain and vascular reactivity were evaluated and histopathology (thoracic aorta and brain) was done.


RESULTS
HSP (100 mg/kg) treatment in l-methionine-treated rats exhibited significant (p < 0.001) dose-dependent activity and reduced behavioural deficits, brain acetylcholinesterase (25.99 ± 2.36 versus 10.73 ± 1.26 μmoles/mg), brain lipid peroxidation (15.25 ± 1.65 versus 6.18 ± 0.74 nM/mg), serum homocysteine (Hcy) (22.37 ± 0.30 versus 11.01 ± 1.01 μg/mL) and serum cholesterol (182.7 ± 2.15 versus 101.5 ± 2.76 mg/dL) and increased brain antioxidant levels. HSP significantly (p < 0.001) reduced endothelial dysfunction (ED) by abolishing the effect of l-methionine on acetylcholine-induced endothelial-dependent relaxation and increased serum nitrite and vascular nitric oxide bioavailability along with the restoration of histological aberrations.


CONCLUSIONS
HSP exerts a protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity.
a Department of Pharmacology, Pharmacology , Anurag Group of Institutions (Formerly Lalitha College of Pharmacy) , Hyderabad , Telangana , India.|b Pharmaceutical Sciences, Research and Development cell , Jawaharlal Nehru Technological University , Kukatpally, Hyderabad , Telangana , India.
B
B
Hemanth Kumar
c Food and Drug Toxicology Research Centre (FDTRC), National Institute of Nutrition (ICMR) , Hyderabad , Telangana , India.
B
B
Dinesh Kumar
a Department of Pharmacology, Pharmacology , Anurag Group of Institutions (Formerly Lalitha College of Pharmacy) , Hyderabad , Telangana , India.|d Maratha Mandal Research Center , Belgaum , Karnataka , India.
Prakash V
PV
Diwan
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D003071:Cognition / Q000187:drug effects; D019610:Cytoprotection; D004195:Disease Models, Animal; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D058851:GPI-Linked Proteins / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology*; D006710:Homocysteine / Q000097:blood; D020138:Hyperhomocysteinemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007189:Indans / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008715:Methionine; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D017208:Rats, Wistar; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D000975:Antioxidants; D058851:GPI-Linked Proteins; D007189:Indans; D018696:Neuroprotective Agents; D009573:Nitrites; D010880:Piperidines; D006710:Homocysteine; D009569:Nitric Oxide; D000077265:Donepezil; D002784:Cholesterol; D008715:Methionine; D006569:Hesperidin; D000110:Acetylcholinesterase; C548246:Ache protein, rat
Acetylcholinesterase; L-NAME; Morris water maze; donepezil; hippocampus; thoracic aorta; video tracking system
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