Neuroprotective Effects of Farnesene Against Hydrogen Peroxide-Induced Neurotoxicity In vitro
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Oxidative stress is highly damaging to cellular macromolecules and is also considered a main cause of the loss and impairment of neurons in several neurodegenerative disorders. Recent reports indicate that farnesene (FNS), an acyclic sesquiterpene, has antioxidant properties. However, little is known about the effects of FNS on oxidative stress-induced neurotoxicity. We used hydrogen peroxide (H2O2) exposure for 6 h to model oxidative stress. Therefore, this experimental design allowed us to explore the neuroprotective potential of different FNS isomers (α-FNS and β-FNS) and their mixture (Mix-FNS) in H2O2-induced toxicity in newborn rat cerebral cortex cell cultures for the first time. For this aim, both MTT and lactate dehydrogenase assays were carried out to evaluate cell viability. Total antioxidant capacity (TAC) and total oxidative stress (TOS) parameters were used to assess oxidative alterations. In addition to determining of 8-hydroxy-2-deoxyguanosine (8-OH-dG) levels in vitro, the comet assay was also performed for measuring the resistance of neuronal DNA to H2O2-induced challenge. Our results showed that survival and TAC levels of the cells decreased, while TOS, 8-OH-dG levels and the mean values of the total scores of cells showing DNA damage (comet assay) increased in the group treated with H2O2 alone. But pretreatment of FNS suppressed the cytotoxicity, genotoxicity and oxidative stress, which were increased by H2O2 in clear type of isomers and applied concentration-dependent manners. The order of antioxidant effectiveness for modulating H2O2-induced oxidative stress-based neurotoxicity and genotoxicity is as β-FNS > Mix-FNS > α-FNS.
KeywordsFarnesene Neuroprotection H2O2 Cultured neuron DNA damage Oxidative stress
We are grateful to our laboratory specialists for their help and efforts in experiments done in the medical genetics and pharmacology laboratories and animal housing.
Conflict of interest
The authors declare that there are no conflicts of interest.
- Cacciatore I, Baldassarre L, Fornasari E, Cornacchia C, Di Stefano A, Sozio P, Cerasa LS, Fontana A, Fulle S, Di Filippo ES, La Rovere RM, Pinnen F (2012) (R)-α-lipoyl-glycyl-l-prolyl-l-glutamyl dimethyl ester codrug as a multifunctional agent with potential neuroprotective activities. Chem Med CHem 7:2021–2029PubMedCrossRefGoogle Scholar
- Isobe C, Abe T, Terayama Y (2010) Levels of reduced and oxidized coenzyme Q-10 and 8-hydroxy-2′-deoxyguanosine in the CSF of patients with Alzheimer’s disease demonstrate that mitochondrial oxidative damage and/or oxidative DNA damage contributes to the neurodegenerative process. J Neurol 257:399–404PubMedCrossRefGoogle Scholar
- Kang SM, Cha SH, Ko JY, Kang MC, Kim D, Heo SJ, Kim JS, Heu MS, Kim YT, Jung WK, Jeon YJ (2012) Neuroprotective effects of phlorotannins isolated from a brown alga, Ecklonia cava, against H2O2-induced oxidative stress in murine hippocampal HT22 cells. Environ Toxicol Pharmacol 34:96–105PubMedCrossRefGoogle Scholar
- Kikuchi Y, Yasuhara T, Agari T, Kondo A, Kuramoto S, Kameda M, Kadota T, Baba T, Tajiri N, Wang F, Tayra JT, Liang H, Miyoshi Y, Borlongan CV, Date I (2011) Urinary 8-OHdG elevations in a partial lesion rat model of Parkinson’s disease correlate with behavioral symptoms and nigrostriatal dopaminergic depletion. J Cell Physiol 226:1390–1398PubMedCrossRefGoogle Scholar
- Obuzor GU, Nwaokolo MI (2010) Composition of essential oil of Nigerian (Niger Delta) grown gardenia jasminoide flower. Int Arch Appl Sci Technol 1:32–36Google Scholar
- Pala S, Gurkan H (2008) The role of free radicals in ethiopathogenesis of diseases. Adv Mol Biol 1:1–9Google Scholar
- Sarikurkcu C, Sabih Ozer M, Cakir A, Eskici M, Mete E (2013) GC/MS evaluation and in vitro antioxidant activity of essential oil and solvent extracts of an endemic plant used as folk remedy in Turkey: Phlomis bourgaei Boiss. Evidence Based Comp Alter Med 2013:293080Google Scholar
- Si CL, Shen T, Jiang YY, Wu L, Yu GJ, Ren XD, Xu GH, Hu WC (2013). Antioxidant properties and neuroprotective effects of isocampneoside II on hydrogen peroxide-induced oxidative injury in PC12 cells. Food Chem Toxicol (in press) doi: 10.1016/j.fct.2013.05.051
- Silva FM, Marques A, Chaveiro A (2010) Reactive oxygen species: a double-edged sword in reproduction. Open Vet Sci J 4:127–133Google Scholar
- Sozio P, Cerasa LS, Laserra S, Cacciatore I, Cornacchia C, Di Filippo ES, Fulle S, Fontana A, Di Crescenzo A, Grilli M, Marchi M, Di Stefano A (2013) Memantine-sulfur containing antioxidant conjugates as potential prodrugs to improve the treatment of Alzheimer’s disease. Eur J Pharm Sci 49:187–198PubMedCrossRefGoogle Scholar
- Togar B (2013) The cytological, biochemical and genetic effects of selected sesquiterpenes on healthy neuron and N2a neuroblastoma cell cultures. PhD’s thesis, Atatürk University, Gradute School of Natural and Applied Sciences, Department of Biology, Erzurum, TurkeyGoogle Scholar
- Tomassoni D, Amenta F, Amantini C, Farfariello V, Di Mannelli Cesare L, Nwankwo IE, Marini C, Tayebati SK (2013) Brain activity of thioctic Acid enantiomers: in vitro and in vivo studies in an animal model of cerebrovascular injury. Int J Mol Sci 14:4580–4595PubMedCentralPubMedCrossRefGoogle Scholar