Hesperidin, a citrus flavonoid, protects against l -methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats

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 14 th 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 (28 th -32 nd 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 < 0.001) dosedependent activity and reduced behavioural deficits, brain acetylcholinesterase (25.99 ± 2.36 versus 10.73 ± 1.26 lmoles/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 lg/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 endothelialdependent 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.ARTICLE HISTORY

Influence of hesperidin and vitamin C on glycemic parameters, lipid profile, and DNA damage in rats treated with sucrose overload

“…In our study, hesperidin cotreatment reduced the DNA damage to a lower level than that observed in sucrose treatment group, in blood and brain samples. Thus, our data reinforce the antioxidant effect of hesperidin previously described by different authors (Adefegha et al 2017, Hemanth Kumar et al 2017, Li and Schluesener 2017.…”

“…On the other hand, VitC can also act as a pro-oxidant agent, while in high concentrations reacts with metals such as iron and copper (Franke et al 2005(Franke et al , 2006. Similarly, depending on dose and molecular environment, hesperidin can show antioxidant (Adefegha et al 2017, Hemanth Kumar et al 2017 or pro-oxidant (Zhang et al 2015a, b) activity.…”

Hyperhomocysteinaemia and vascular injury: advances in mechanisms and drug targets

“…Genistein, a soy isoflavone, blocks homocysteine‐induced pathogenic alterations in human ECs via down‐regulating antioxidative pathways (Han et al ., ). Hesperidin, a citrus flavonoid, protects against HHcy induced by a high Met diet, by blocking oxidative stress, EC dysfunction and neurotoxicity in Wistar rats (Hemanth Kumar et al ., ). Huang Qi decoction (HQD) is a traditional Chinese medical formula, and its components exert antioxidant effects.…”

Hesperidin as a Neuroprotective Agent: A Review of Animal and Clinical Evidence

“…Moreover, hesperidin exerted the protective effect on vascular dementia (VD) in the rat model of l-methionine-induced hyperhomocysteinemia (HHcy). Endothelial dysfunction in addition to cognitive deteriorates, mediated by HHcy, was attenuated by hesperidin via a dose-dependent mechanism, in which nitrite and serum Hcy levels with MDA levels were decreased, AChE activity was inhibited, and the levels of GSH, SOD, and CAT were increased [92,93]. Similar results were also achieved after coadministration of hesperidin and donepezil in the scopolamine induced amnesia model, corroborating the prominent role of hesperidin in ameliorating dementia and cognitive deficits of AD [94].…”