The effect of epicatechin on oxidative stress and mitochondrial damage induced by homocycteine using isolated rat hippocampus mitochondria

Fatemeh Shaki, Yaghoub Shayeste, Mohammad Karami, Esmaeil Akbari, Mahdi Rezaei, Ramin Ataee

Abstract


Oxidative stress and mitochondrial dysfunction are the main suggested mechanisms for neurodegenerative diseases. In this study, we have evaluated the effects of epicatechin (EC) on mitochondrial damage induced by homocycteine (Hcy) using isolated rat hippocampus mitochondria in vivo. EC (50 mg/kg) was gavaged daily for a period of 10 days, starting 5 days prior to Hcy (0.5 μmol/μL) intra hippocampus injection in rats. Mitochondria were isolated from brain by different centrifuge techniques. Mitochondrial function was assayed by MTT test. Also, mitochondrial swelling and oxidative stress markers, such as reactive oxygen species (ROS), lipid peroxidation and glutathione (GSH), were assayed. Hcy induced mitochondrial dysfunction and swelling. Increase in ROS formation, lipid peroxidation, and decreased GSH were observed after Hcy treatment in isolated brain mitochondria. Furthermore, oral administration of EC significantly decreased the lipid peroxidation and ROS levels and also increased GSH levels. Also, EC treatment significantly improved mitochondrial function. As EC indicated protective effects against oxidative stress and mitochondrial damage induced by Hcy, it is suggested for further trials for prevention or treatments of neurodegenerative disorders such as Alzheimer disease.


Keywords


Epicatechin; Homocycteine; Oxidative stress; Mitochondria; Neurodegenerative

Full Text:

PDF

References


Mattson MP. Metal‐catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders. Ann of the New York Acad of Sci. 2004;1012(1):37-50.

Lepoivre M, Flaman J-M, Bobé P, Lemaire G, Henry Y. Quenching of the tyrosyl free radical of ribonucleotide reductase by nitric oxide. Relationship to cytostasis induced in tumor cells by cytotoxic macrophages. J Biol Chem. 1994;269(34):21891-21897.

Massimo CMA, Mastrocola R, Gallicchio M, Carolina Rosa A, Dianzani C, Danni O, et al. Modulation of the oxidative stress and inflammatory response by PPAR-γ agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion. Eur J Pharmacol. 2006;530:70–80.

Collino M, Aragno M, Mastrocola R, Gallicchio M, Rosa AC, Dianzani C, et al. Modulation of the oxidative stress and inflammatory response by PPAR-γ agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion. Eur J Pharmacol. 2006;530(1-2):70-80.

Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS. Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model. Proc Natl Acad Sci USA. 2010;107(43):18670-18675.

Agnati L, Genedani S, Rasio G, Galantucci M, Saltini S, Filaferro M, et al. Studies on homocysteine plasma levels in Alzheimer’s patients. Relevance for neurodegeneration. J Neural Transm. 2005;112(1):163-169.

Ataie A, Sabetkasaei M, Haghparast A, Moghaddam AH, Kazeminejad B. Neuroprotective effects of the polyphenolic antioxidant agent, curcumin, against homocysteine-induced cognitive impairment and oxidative stress in the rat. Pharm Biochem Behav. 2010;96(4):378-385.

Cuevas E, Limón D, Pérez-Severiano F, Díaz A, Ortega L, Zenteno E, et al. Antioxidant effects of epicatechin on the hippocampal toxicity caused by amyloid-beta 25-35 in rats. Eur J Pharmacol. 2009;616(1):122-127.

Soung HS, Wang MH, Tseng HC, Fang HW, Chang KC. (-) Epigallocatechin-3-gallate decreases the stress-induced impairment of learning and memory in rats. Neurosci Lett. 2015;602:27-32.

Streck EL, Vieira PS, Wannmacher CM, Dutra-Filho CS, Wajner M, Wyse AT. In vitro effect of homocysteine on some parameters of oxidative stress in rat hippocampus. Metab Brain Dis. 2003;18(2):147-154

Zaveri NT. Green tea and its polyphenolic catechins: medicinal uses in cancer and noncancer applications. Life Sci. 2006;78:2073–2080

Sutherland BA, Rahman RM, Appleton I. Mechanisms of action of green tea catechins, with a focus on ischemia-induced neurodegeneration. J Nut Biochem. 2006;17(5): 291–306

Shah Zale R, Ahmad AS, Kensler A, Yamamoto M, Biswal S, et al. The flavanol (-)-epicatechin prevents stroke damage through the Nrf2/HO1 pathway. J Cereb Blood Flow Metab. 2010;30(12):1951–1961.

Cuevas E, Limón D, Pérez-Severiano F, Díaz A, Ortega L, Zenteno E, et al. Antioxidant effects of epicatechin on the hippocampal toxicity caused by amyloid – beta 25 – 23 in rats. Eur J Pharmacol. 2009;616(1-3):122-127.

Gómez-Guzmán M, Jiménez R, Sánchez M, Zarzuelo MJ, Galindo P, Quintela AM, et al. Epicatechin lowers blood pressure, restores endothelial function, and decreases oxidative stress and endothelin-1 and NADPH oxidase activity in DOCA-salt hypertension. Free Radic Biol Med. 2012;52:70–79.

Nath S, Bachani M, Harshavardhana D, Steiner JP. Catechins protect neurons against mitochondrial toxins and HIV proteins via activation of the BDNF pathway. J Neurovirol. 2012;18(6):445-455.

Shaki F, Hossein MJ, Ghazi-Khansari M, Pourahmad J. Toxicity of depleted uranium on isolated rat kidney mitochondria. Biochim Biophys Acta. 2012;1820(12):1940–1950.

Sadegh C, Ronald PS. The spectroscopic determination of aqueous sulfite using Ellman's reagent. MURJ. 2003;8:39–43.

Pérez-Severiano F, Salvatierra-Sánchez R, Rodríguez-Pérez M, Cuevas-Martínez EY, Guevara J, Limón D. S-allylcysteine prevents amyloid-ß peptide-induced oxidative stress in rat hippocampus and ameliorates learning deficits. Eur J Pharmacol. 2004;489(3): 197–202.

Shaki F, Pourahmad J. Mitochondrial toxicity of depleted uranium: protection by beta-glucan. Iran J Pharm Res. 2012;12:131-140.

Petrozzi L, Ricci G, Giglioli NJ, Siciliano G, Mancuso M. Mitochondria and neurodegeneration. Biosci Rep. 2007;27:87-104.

Federico A, Cardaioli E, Da Pozzo P, Formichi P, Gallus GN, Radi E. Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci. 2012;322(1-2):254-262.

Yan MH, Wang X, Zhu X. Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. Free Radic Biol Med. 2013;62:90-101.

Agnati LF GS, Rasio G. Studies on homocysteine plasma levels in Alzheimer's patients for neurodegeneration. J Neural Transm. 2005;112: 163–169.

Kim JH, Cho SY, Lee JH, Jeong SM, Yoon IS, Lee BH, et al. Neuroprotective effects of ginsenoside Rg3 against homocysteine-induced excitotoxicity in rat hippocampus. Brain Res. 2007;1136:190–199.

Shaki JP, Hosseini MM, Ghazi-Khansari F. Depleted uranium disrupted the bioenergetics of liver mitochondria: a potential mechanism of fatigue syndrome. Res Pharm Sci. 2012;7(5):S131.

Spencer JP, Schroeter H, Crossthwaithe AJ, Kuhnle G, Williams RJ, Rice-Evans C. Contrasting influences of glucuronidation and O-methylation of epicatechin on hydrogen peroxide-induced cell death in neurons and fibroblasts. Free Radic Biol Med. 2001;31(9):1139–1146.

Baba S, Osakabe N, Natsume M, Muto Y, Takizawa T, Terao J. In vivo comparison of the bioavailability of (+)-catechin, (−)-epicatechin and their mixture in orally administered rats. J Nutr. 2001;131(11):2885–2891.

Mohsen MA, Marks J, Kuhnle G, Rice-Evans C, Moore K, Gibson G, et al. The differential tissue distribution of the citrus flavanone naringenin following gastric instillation. Free Radic Res. 2004;38(12):1329–1340.

Longpré F, Garneau P, Christen Y, Ramassamy C. Protection by EGb 761 against beta-amyloid-induced neurotoxicity: involvement of NF-kappaB, SIRT1, and MAPKs pathways and inhibition of amyloid fibril formation. Free Radic Biol Med. 2006;41(12):1781–1794.

Man WW. An investigation into the neuroprotective effects of estrogen and progesterone in a model of homocysteine – induced neurodegeneration. Thesis of Master in Pharmacy. South Africa: Rhodes University E-Publishing. 2005. pp.65-180.

Praticò D, Delanty N. Oxidative injury in diseases of the central nervous system: focus on Alzheimer’s disease. Am J Med. 2000;109(7):577-585.

Ban JY, Jeon SY, Bae K, Song KS, Seong YH. Catechin and epicatechin from Smilacis chinae rhizome protect cultured rat cortical neurons against amyloid β protein (25–35)-induced neurotoxicity through inhibition of cytosolic calcium elevation. Life Sci. 2006;79(24):2251–2259.

Zhong Q, Putt DA, Xu F, Lash LH. Hepatic mitochondrial transport of glutathione: studies in isolated rat liver mitochondria and H4IIE rat hepatoma cells. Arch Biochem Biophys. 2008;474(1):119-127.

Hosseini MJ, Shaki FS, Ghazi-Khansari M, Pourahmad J. Toxicity of arsenic (III) on isolated liver mitochondria: a new mechanistic approach. Iran J Pharm Res. 2013;12(Suppl):121-138.

Nath S, Bachani M, Harshavardhana D, Steiner JP. Catechins protect neurons against mitochondrial toxins and HIV proteins via activation of the BDNF pathway. J Neurovirol. 2012;18(6):445-455.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.