Hesperidin, a citrus flavonoid, protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats
Authors: Prakash V Diwan
B Hemanth Kumar
B Dinesh Kumar
Journal: Pharmaceutical biology (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Acetylcholinesterase; L-NAME; Morris water maze; donepezil; hippocampus
Affiliations: 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., c Food and Drug Toxicology Research Centre (FDTRC), National Institute of Nutrition (ICMR) , Hyderabad , Telangana , India., d Maratha Mandal Research Center , Belgaum , Karnataka , India.

Abstract:  Context: 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. Materials and 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 14th day 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-32nd day). 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 &lt; 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 &lt; 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. Conclusion: HSP exerts a protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity. 

Retracted: No

PubPeer comments:
 Figure 6D and 6E appear to overlap (blue boxes), but I believe they are supposed to show 2 different concentrations of HSP. *** ![file] , 
 In addition to the similarities between two panels in Figure 6, several panels appear to also look similar to panels in Figure 5 in another paper by the same authors. That paper is  Effects of fisetin on hyperhomocysteinemia- induced experimental endothelial dysfunction and vascular dementia by Boyina Hemanth Kumar et al., Canadian Journal of Physiology and Pharmacology (2017), DOI: 10.1139 cjpp-2016-0147 ( CJPP paper ). See: https: pubpeer.com publications BE828DC185106CA7FEE761B303D63D Colored boxes indicate similarities or potential overlapping areas between Figure 5 in the CJPP paper (this paper) and Figure 6 of the PB paper. * Dark blue boxes: a common area between CJPP Figure 5 panels A (control rat) and B (vehicle rat), and PB Figure 6 panels D (50 mg kg HSP) and E (100 mg kg HSP) * Medium blue boxes: CJPP Figure 5 panels B (vehicle rat) with PB Figure 6 panel D (50 mg kg HSP) * Light blue boxes: CJPP Figure 5 panels A (control rat) with PB Figure 6 panel E (100 mg kg HSP) * Moss boxes: CJPP Figure 5 panel G (FST-Per se rat) with PB Figure 6 panel A (DMSO treated rat) * Aqua boxes: CJPP Figure 5 panel H (Donepezil rat) with PB Figure 6 panel G (Donepezil treated rat) ![file] , 
 **Fig 6 is amended and this paper is republished ** https: www.tandfonline.com doi figure 10.1080 13880209.2016.1231695?scroll=top needAccess=true https: doi.org 10.1080 13880209.2016.1231695 , 
 u201cThis article has been republished with minor changes. These changes do not impact the academic content of the article.u201d This comment is appended at the end of the corrected article, making it difficult for readers to decide for themselves whether these issues affect their confidence in the results. ,