Neuroprotective Effect of Lycopene Against PTZ-induced Kindling Seizures in Mice: Possible Behavioural, Biochemical and Mitochondrial Dysfunction

Abstract

Oxidative stress and mitochondrial dysfunction are the major contributing factors in the pathophysiology of various neurological disorders. Recently, antioxidant therapies aimed at reducing oxidative stress gained a considerable attention in epilepsy treatment. Lycopene, a carotenoid antioxidant, has received scientific interest in recent years. So, the present study has been designed to evaluate the neuroprotective effect of lycopene against the pentylenetetrazol (PTZ)-induced kindling epilepsy. Laca mice received lycopene (2.5, 5 and 10 mg/kg) and sodium valproate for a period of 29 days and PTZ (40 mg/kg i.p (Intraperitoneal)) injection on alternative days. Various behavioural (kindling score), biochemical parameters (lipid peroxidation, superoxide dismutase, reduced glutathione, catalase and nitrite) and mitochondrial enzyme complex activities (I, II and IV) were assessed in the brain. Results depicted that repeated administration of a sub-convulsive dose of PTZ (40 mg/kg) significantly increased kindling score, oxidative damage and impaired mitochondrial enzyme complex activities (I, II and IV) as compared with naive animals. Lycopene (5 and 10 mg/kg) and sodium valproate (100 mg/kg) treatment for a duration of 29 days significantly attenuated kindling score, reversed oxidative damage and restored mitochondrial enzyme complex activities (I, II and IV) as compared with control. Thus, present study demonstrates the neuroprotective potential of lycopene in PTZ-induced kindling in mice.

NRF2 as a Therapeutic Target in Neurodegenerative Diseases

“…It also attenuated Ab-induced mitochondrial damage in isolated cortical neurons (Qu et al, 2011;Qu et al, 2016) and reduced proinflammatory cytokines in the brain of Ab-exposed animals (Liu et al, 2018). Similar effects of lycopene on oxidative and mitochondrial damage have been demonstrated in a pentylenetetrazol-induced model of seizure where it also decreased convulsive activity (Bhardwaj and Kumar, 2016;Kumar et al, 2016). Lycopene also decreased markers of oxidative stress and reduced neuronal cell loss in models of PD and stroke (Prema et al, 2015;Lei et al, 2016) and was able to attenuate BBB disruption and neurological deficits in a model of subarachnoid hemorrhage (Wu et al, 2015).…”

Lycopene as a Natural Antioxidant Used to Prevent Human Health Disorders

“…Decreased low-density lipoprotein-cholesterol (LDL), total cholesterol (TC), and thiobarbituric acid-reacting substances [58] Lowered very-low-density lipoprotein-cholesterol (VLDL), triglycerides (TG) and increased high-density lipoprotein-cholesterol (HDL) level [59] Decreased inflammatory factors (CRP, interleukin (IL)-6), pulse wave velocity, adhesion molecules and endothelial function [60] Lowered Improved mitochondrial enzymatic activities, kindling score, oxidative stress [74] Decreased impairment in biochemical, behavioral, neuroinflammatory and neurochemical markers [75] Boneprotective Osteoblasts differentiation improved [76] Modified the biomarkers of serum osteocalcin, bone metabolism, crosslinked carboxyterminal telopeptides and N-terminal propeptide of type 1 collagen in serum Downregulated the osteoclast differentiation concurrent Up-regulated the osteoblasts alongside GPx, SOD, and CAT activities [77] Targeting reproductive disorders…”

“…Rats were assessed for various behavioral and biochemical parameters (SOD, lipid peroxidation, CAT, decreased GSH and nitrite) and activities of the enzymes of mitochondria (I, II, and IV) in the brain. Based on the findings, lycopene (5, 10 mg/kg) considerably improved mitochondrial enzymatic activities, kindling score, and oxidative stress as compared to control [74]. The neuroprotective role of lycopene was also studied in a male C57BL/6 mice model of bilateral common carotid artery occlusion (BCCAO).…”

Lycopene depresses glutamate release through inhibition of voltage-dependent Ca2+entry and protein kinase C in rat cerebrocortical nerve terminals

“…In addition to these health benefits, lycopene is also thought to have brain protection. This concept stems from the observation that lycopene can penetrate the blood-brain barrier (Khachik et al 2002), ameliorate pentylenetetrazol-induced seizures (Bhardwaj and Kumar 2016;Kumar et al 2016), as well as attenuate ischemia-or neurotoxins-induced brain injury and memory impairment in experimental animals (Fujita et al 2013;Lei et al 2016;Prakash and Kumar 2013;Sachdeva and Chopra 2015). Furthermore, it was reported that dietary intake of lycopene can reduce the risks D r a f t of neurodegenerative disorders, especially Alzheimer's disease (Bun et al 2015).…”

“…Furthermore, it was reported that dietary intake of lycopene can reduce the risks D r a f t of neurodegenerative disorders, especially Alzheimer's disease (Bun et al 2015). Although the underlying mechanism through which lycopene exerts its neuroprotective effect has not been clearly elucidated, inhibited inflammatory processes, antioxidant activity, oxygen-free radicals scavenging, and improved mitochondrial dysfunction have been implicated (Bhardwaj and Kumar 2016;Fujita et al 2013;Sachdeva and Chopra 2015).…”