Effect of naringenin (A naturally occurring flavanone) against pilocarpine-induced status epilepticus and oxidative stress in mice

Abstract

Background:Epilepsy is a disorder of the central nervous system characterized by recurrent seizures. It is a very common disease in which approximately 30% of patients do not respond favourably to treatment with anticonvulsants. Oxidative stress is associated with neuronal damage arising from epileptic seizures. The present study investigated the effects of naringenin in pilocarpine-induced epilepsy in mice. Naringenin, one of the most frequently occurring flavanone in citrus fruits, was evaluated for its shielding effect against the pilocarpine induced behavioural, oxidative and histopathological alterations in rodent model of epilepsy.Methodology:Epilepsy was induced by giving pilocarpine (300mg/kg) and sodium valproate (300mg/kg) was given as standard anti-epileptic drug Pilocarpine was administered (300 mg /kg body weight) intraperitoneally to the mice on 15th day while naringenin was administered orally (20 and 40 mg/kg body weight) for 15 days prior to administration of pilocarpine.Results:The intraperitoneal administration of pilocarpine enhanced lipid peroxidation, caused reduction in antioxidant enzymes, viz., catalase, superoxide dismutase and glutathione reductase. Treatment of mice orally with naringenin (20 mg/kg body weight and 40 mg/kg body weight) resulted in a significant decrease in lipid peroxidation. There was significant recovery of glutathione content and all the antioxidant enzymes studied. Also in case of behavioural parameters studied, naringenin showed decrease in seizure severity. All these changes were supported by histological observations, which revealed excellent improvement in neuronal damage.Conclusion:The higher dose of naringenin was more potent in our study and was comparable to the standard drug (sodium valproate) in effectiveness.SUMMARY Naringenin ameliorated the development of ROS formation in hippocamus.Naringenin helped in recovery of antioxidant enzymes.Naringenin decreased seizure severity.Naringenin treatment reduced lipid peroxidation. Abbreviations used: 6-OHDA: 6-hydroxydopamine, AED: Anti epileptic drugs, AIDS: Acquired immune deficiency syndrome, ANOVA: Analysis of variance, ATP: Adenosine triphosphate, CA: Cornu ammonis, CAT: Catalase, DG: Dentate gyrus, EDTA: Ethylenediamine tetra acetic acid, GR: Glutathione reductase, GSH: Glutathione reduced, HCl: Hydrochloric acid, IL-1β: Interleukin 1 beta, LPO: Lipid peroxidation, MDA: Malondialdehyde, NADPH: Nicotinamide adenine dinucleotide phosphate, PMS: post mitochondrial supernatant, SE: Status epilepticus, SEM: Standard error of the mean, SOD Superoxide dismutase, TBA: Thiobarbituric acid, TBARS: Thiobarbituric acid reactive substance, TLE: Temporal lobe epilepsy, TNF-α: Tumor necrosis factor alpha

TRPV4-induced inflammatory response is involved in neuronal death in pilocarpine model of temporal lobe epilepsy in mice

“…Mice were intraperitoneally injected with pilocarpine (300 mg/kg) to induce SE 17 . Methylscopolamine (1 mg/kg) was injected 20 min before pilocarpine injection to antagonize peripheral muscarinic activity.…”

Beneficial effects of naringenin in liver diseases: Molecular mechanisms

“…Therefore, there are mechanisms in charge of maintaining the GSH/GSSG balance; for example, glutathione reductase (GR or GSR) is responsible of GSSG reduction to the disulfide form (GSH) at the expense of NADPH[ 55 - 57 ]. It has been reported that naringenin increased the GSH/GSSG ratio[ 59 , 61 ] by improving GR mRNA levels and activity in the liver[ 44 , 63 - 66 ] and in other organs[ 67 , 68 ] (Figure 4 ).…”

“…SOD catalyzes the reaction in which O 2 • is converted to H 2 O 2 , a more stable species but that at high concentrations is harmful to cells; in turn, CAT eliminates excess H 2 O 2 , generating water[ 69 ]. Naringenin significantly increases SOD enzyme activity in different models of liver damage induced by oxidative stress[ 44 , 50 , 52 , 62 - 65 , 67 , 70 - 74 ]. This effect is associated with the ability of this flavonoid to increase enzyme protein levels in the liver and other organs[ 58 , 59 , 68 ].…”

“…This effect is associated with the ability of this flavonoid to increase enzyme protein levels in the liver and other organs[ 58 , 59 , 68 ]. Naringenin can prevent CAT activity decrement after damage to several tissues[ 44 , 49 , 50 , 52 , 62 - 65 , 67 , 70 - 74 ] by increasing protein[ 58 , 59 , 68 ] and mRNA levels[ 43 ].…”

Seizure-Induced Oxidative Stress in Status Epilepticus: Is Antioxidant Beneficial?

“…It has significant antioxidant properties, affected plasma lipid levels and antioxidant activity [ 144 ], protected mice against radiation-induced DNA damage [ 145 ], or defended ferric iron-induced oxidative damage in HepG2 cells [ 146 ]. In pilocarpine-induced status epilepticus, reduction of antioxidant enzymes such as catalase, superoxide dismutase (SOD), and glutathione reductase was found in the hippocampus, and naringenin can reduce ROS formation, restore antioxidant enzymes and lessen seizure severity [ 116 ]. No clinical trial was found regarding “brain disease and Naringenin” from ClinicalTrials.gov.…”