Dokozaheksaenojska kiselina modulira nivo oksidativnog stresa i monoamina u mozgu dijabetičkih pacova izazvanih streptozotocinom.
Ključne reči:
Dijabetes - Dokozaheksenska kiselina - Oksidativni stres - Neurotransmiteri - Insulin.
Sažetak
Kako dijabetes melitus (DM) raste u mnogim zemljama, primećena je manja prevalencija DM tipa2 i drugih poremećaja metabolizma glukoze u populacijama koje konzumiraju veće količine n-3 polinezasićenih masnih kiselina, uglavnom prisutnih u ribi. Dokozaheksaenojska kiselina (DHA) potrebna je za kontinuirano održavanje centralnog nervnog sistema radi funkcionisanja mozga i kao važan signalni molekul. Cilj je da se istakne uloga DHA u kontroli glikemijskih mera i moduliranju oksidantnog / antioksidativnog statusa i neurotransmitera u mozgu pacova dijabetičkih pacova. Dijabetes je indukovan jednim s.c. injekcija streptozotocina (STZ) (6,0 mg / 0,5 ml / 100 g telesne težine). Eksperimentalni muški pacovi vister (n = 40) nasumično su podeljeni u četiri grupe kontrole, DHA grupa STZ-dijabetičar i STZ + DHA. Svim pacovima su odsečene glave nakon 30 dana da bi se procenili nivoi glukoze i insulina, takođe su procenjeni oksidativni stres u mozgu i nivo monoamina. DHA administracija je značajno poboljšala nivo glukoze u krvi i insulina natašte u poređenju sa DHA + STZ grupom i smanjila nivo 8-hidroksi-2′-deoksiguanosine u njihovom urinu. Pored toga, tretman DHA pacovima tretiranim STZ-om pokazao je smanjeni povišeni sadržaj malondialdehida i produkt napredne oksidacione belančevine i značajno povećan sadržaj glutationa u mozgu pacova tretiranih DHA + STZ-om i smanjio povišeni nivo monoamina u mozgu pacova. U zaključku; DHA je takođe modulirao povišeni nivo oksidativnog stresa i neurotransmitera, kao i aktivnost acetilholinesteraze u mozgu dijabetičara pacova, povećavajući nivo insulina u njihovim serumima.
Reference
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(23) Jeong YK, Kim H. A Mini-Review on the Effect of Docosahexaenoic Acid (DHA) on Cerulein-Induced and Hypertriglyceridemic Acute Pancreatitis Y A Mini-Review on the Effect of Docosahexaenoic Acid (DHA) on Cerulein-Induced and Hypertriglyceridemic Acute Pancreatitis. Int J Mol Sci 2017; 18:2239. https://DOI: 10.3390/ijms18112239
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(27) Casanas-Sanchez V, Perez JA, Fabelo N, Quinto-Alemany D, Díaz M L () Docosahexaenoic (DHA) modulates phospholipid hydroperoxide glutathione peroxidase (Gpx4) gene expression to ensure self-protection from oxidative damage in hippocampal cells. Front Physiol 2015; 6:203. https://doi.org/10.3389/fphys.2015.00203
(28) Arnal E, Miranda M, Barcia J et al. Lutein and docosahexaenoic acid prevent cortex lipid peroxidation in streptozotocin-induced diabetic rat cerebral cortex. Neuroscience 2010; 166 :271–278. https://DOI: 10.1016/j.neuroscience.2009.12.028.
(29) Sakai C, Ishida M, Ohba H et al.. Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced DNA ; damage in vascular endothelial cells. PLoS ONE 2017; 12: e0187934.
(30) Haag M. Essential fatty acids and the brain, Can. J Psychiatry 2003; 48:195–203. https://doi.org/10.1177/070674370304800308
(31) Schwarzenberg SJ, Georgieff MK. Committee on Nutrition Advocacy for improving nutrition in the first 1000 days to support childhood development and adult health Pediatrics. 2018; 141. https://DOI: 10.1542/peds.2017-3716
(32) Hashimoto M, Hossain S, Al Mamun A et al. . Docosahexaenoic acid: one molecule diverse functions. Cri Rev Biotech 2017; 37: 579-597.
https://doi: 10.1080/07388551.2016.1207153. Epub 2016 Jul 17.
(33) Mun JG, Legette LC, Ikonte CJ et al. Choline and DHA in Maternal and Infant Nutrition: Synergistic Implications in Brain and Eye Health. Nutrients 2019; 11: 1125. https://DOI: 10.3390/nu11051125
(34) Pifferi F, Roux F, Langelier B et al. (n-3) polyunsaturated fatty acid deficiency reduces the expression of both isoforms of the brain glucose transporter GLUT1 in rats. J Nutr 2005; 135: 2241-6. https://DOI: 10.1093/jn/135.9.2241
(35) Champeil-Potokar G, Chaumontet C, Guesnetp L et al. Docosahexaenoic acid (22: 6n-3) enrichment of membrane phosphor- lipids increases gap junction coupling capacity in cultured astrocytes. Eur J Neurosci 2006; 24: 3084-3090. https://doi: 10.1111/j.1460-9568.2006.05185.x.
(36) Jones CR, Arai T, Rapoport SI. Evidence for the involvement of docosahexaenoic acid in cholinergic stimulated signal transduction at the synapse. Neurochem Res. 1997; 22:663–670. https://DOI: 10.1023/a:1027341707837
(37) Rapoport SI, Ramadan E, Basselin M. Imaging plasma docosahexaenoic acid (DHA) incorporation into the brain in vivo,as a biomarker of brain DHA: Metabolism and neurotransmission. OCL 2011; 18: 246-250. https://DOI: 10.1051/ocl.2011.0396
(38) Kim HY, Spector AA, Xiong ZM. A synaptogenic amide N-docosahexaenoyl- ethanolamide promotes hippocampal development. Prostaglandins Lipid Med 2011; 96:114–120. https://doi: 10.1016/j.prostaglandins.2011.07.002
(39) Zimmer L, Hembert S, Durand G et al. Chronic n-3 polyunsaturated fatty acid diet-deficiency acts on dopamine metabolism in the rat frontal cortex: a microdialysis study. Neurosci Lett 1998; d240:177–181. https://DOI: 10.1016/s0304-3940(97)00938-5
(40) Mathieu G, Denis S, Langelier B et al. DHA enhances the noradrenaline release by SH-SY5Y cells. Neurochem Int 2010; 56:94–100.
(41) Onuki Y, Morishita M, Chiba Y et al. Docosahexaenoic acid and eicosapentae- noic acid induce changes in the physical properties of a lipid bilayer model membrane. Chem Pharm Bull 2006; 54:68–71. https://DOI: 10.1248/cpb.54.68
(42) Hashimoto M, Hossain S, Shimada T, Shido O. Docosahexaenoic acid-induced protective effect against impaired learning in amyloid beta-infused rats is associated with increased synaptosomal membrane fluidity. Clin Exp Pharmacol Physiol 2006; 33: 934–939.
(43) Bandarra NM, Lopes PA, Martins SV et al. Docosahexaenoic acid at the sn-2 position of structured triacylglycerols improved n-3 polyunsaturated fatty acid assimilation in tissues of hamsters. Nutr Res 2016; 36:452–463. https://DOI: 10.1016/j.nutres.2015.12.015 PMID: 27101763
(44) Marcheselli VL, Hong S, Lukiw WJ et al. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 2003; 278: 43807–43817. https://DOI: 10.1074/jbc.M305841200
(45) Zhao Y, Calon F, Julien C et al. Doco-sahexaenoic acid-derived neuro-protectin D1 induces neuronal survival via secretase and PPARc-mediated mechanisms in Alzheimer’s disease models. PLoS One 2011; 6: e15816. DOI: 10.1371/journal.pone.0015816
(2) Sarbolouki S, Javanbakht MH, Derakhshanian H et al. Eicosapentaenoic acid improves insulin sensitivity and blood sugar in overweight type 2 diabetic mellitus patients: A double-blind randomised clinical trial. Sing Med J 2013; 54:387-90.
https://doi: 10.11622/smedj.2013139.
(3) Mozaffarian D, Wu JH. (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary?. J Nutr 2012; 142: 614S–625S. https://doi: 10.3945/jn.111.149633
(4) Grosso G, Micek A, Marventano S et al. Dietary n-3 PUFA, fish consumption and depression: A systematic review and meta-analysis of observational studies. J Affect Disord 2016; 205: 269–281. https://doi: 10.1016/ j.jad. 2016.08.011. Epub 2016 Aug 16.
(5) Smink W, Gerrits WJ, Gloaguen M et al. Linoleic and α-linolenic acid as precursor and inhibitor for the synthesis of long-chain polyun-saturated fatty acids in liver and brain of growing pigs. Animal 2012; 6: 262–270. https://doi.org/10.1017/S1751731111001479
(6) Bazan G, Eady N, Khoutorova L et al. Novel aspirin-triggered neuroprotectin D1 attenuates cerebral ischemic injury after experimental stroke. Exp Neurol 2012; 236:122–130. https://DOI: 10.1016/j.expneurol.2012.04.007
(7) Uchiyama S, Yamaguchi M. Alteration in serum and bone component findings induced in streptozotocin-diabetic rats is restored by zinc acexamate. Int J Mol Med 2003; 12:949–954.
https://doi.org/10.3892/ijmm.12.6.949
(8) Mannaa F, Ahmed HH, Estefan SF et al. Saccharomyces cerevisiae intervention for relieving flutamide-induced hepatotoxicity in male rats. Die Pharm Int J Pharm Sci 2005; 60:689–695
(9) Hussein J, Refaat E, Morsy S et al. Green tea attenuates experimental hepatitis in context of oxidative stress. J Appl Pharm Sci 2013; 3:124. https://DOI: 10.7324/JAPS.2013.31222
(10) Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 1969; 6:24–27.
(11) Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1982; 95:351–358.
(12) Beutler E. Improved method for the determination of blood glutathione. J Lab Clin Med 1963; 61:882–888.
(13) Hussein J, Abo Elmatty D, Medhat D et al. Flaxseed oil attenuates experimental liver hepatitis. Der Pharm Lett 2016; 8:142–150.
(14) Larsen K. Creatinine assay by a reaction-kinetic principle. Clin Chim Acta 1972; 41:209–217
(15) Hussein J, El-Khayat Z, Abdel Latif Y et al. Evaluation of brain monoamines in diabetic rats treated with quercetin. J Chem Pharm Res 2014; 6: 384–390
(16) Ellman GL, Courtney KD, Andres V Jr et al. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; .7:88–95
(17) El-Yamany NA, Mahmoud SM, Abdel Moneim AE. The Ameliorative Effect of Panax Ginseng Extract on Norepinephrine Dopamine and Serotonin Levels in Different Brain Regions of Alloxan-Induced Diabetic Rats. Egy J Zoo 2004; 43:347-366.
(18) Mohamed MI, Sharkawy MA, AbdelRahman T et al. Effect of Panax Ginseng on The Activity of Cholinesterase in Different Tissues of Experimentally-Induced Diabetes in Rats. J Egypt Soc Toxicol 2007; 37: 95-106.
(19) Hussein J, El-Naggar M, Badawy E. et al. Homocysteine and Asymmetrical Dimethylarginine in Diabetic Rats Treated with Docosahexaenoic Acid–Loaded Zinc Oxide Nanoparticles. Appl Biochem Biotechnol 2020; E-published Jan. 10.1007/s12010-020-03230-z https://doi.org/10.1007/s12010-020-03230-z.
(20) Hussein J, Attia MF, ElBana M et al. Solid state synthesis of docosahexaenoic acid-loaded zinc oxide nanoparticles as a potential antidiabetic agent in rats. Int J Bio Macromol. 2019; 140:1305–1314. https://DOI: 10.1016/j.ijbiomac.2019.08.201
(21) Oh DY, Talukdar S, Bae EJ et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2020; 142: 687–98. https://doi: 10.1016/j.cell.2010.07.041
(22) Casañas-Sánchez V, Pérez JA, Fabelo N et al. Addition of docosahexaenoic acid, but not arachidonic acid, activates glutathione and thioredoxin antioxidant systems in murine hippocampal HT22 cells: Potential implications in neuroprotection. J Neurochem 2014; 131: 470–483. https://DOI: 10.1111/jnc.12833
(23) Jeong YK, Kim H. A Mini-Review on the Effect of Docosahexaenoic Acid (DHA) on Cerulein-Induced and Hypertriglyceridemic Acute Pancreatitis Y A Mini-Review on the Effect of Docosahexaenoic Acid (DHA) on Cerulein-Induced and Hypertriglyceridemic Acute Pancreatitis. Int J Mol Sci 2017; 18:2239. https://DOI: 10.3390/ijms18112239
(24) Li ZG, Zhang W, Grunberger G et al. Hippocampal neuronal apoptosis in type 1 diabetes. Brain Res 2002; 946:221–231. https://DOI: 10.1016/s0006-8993(02)02887-1
(25) Alvarez-Nölting R, Arnal E, Barcia JM et al. Protection by DHA of early hippocampal changes in diabetes: possible role of CREB and NF-κB. Neurochem Res 2012; 37:105–115. https://DOI: 10.1007/s11064-011-0588-x
(26) Merad-Boudia M, Nicole A, Santiard-Baron D et al. Mitochondrial impairment as an early event in the process of apoptosis induced by glutathione depletion in neu¬ronal cells: relevance to Parkinson's disease. Biochem Pharmacol 1998; 56:645–655.
(27) Casanas-Sanchez V, Perez JA, Fabelo N, Quinto-Alemany D, Díaz M L () Docosahexaenoic (DHA) modulates phospholipid hydroperoxide glutathione peroxidase (Gpx4) gene expression to ensure self-protection from oxidative damage in hippocampal cells. Front Physiol 2015; 6:203. https://doi.org/10.3389/fphys.2015.00203
(28) Arnal E, Miranda M, Barcia J et al. Lutein and docosahexaenoic acid prevent cortex lipid peroxidation in streptozotocin-induced diabetic rat cerebral cortex. Neuroscience 2010; 166 :271–278. https://DOI: 10.1016/j.neuroscience.2009.12.028.
(29) Sakai C, Ishida M, Ohba H et al.. Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced DNA ; damage in vascular endothelial cells. PLoS ONE 2017; 12: e0187934.
(30) Haag M. Essential fatty acids and the brain, Can. J Psychiatry 2003; 48:195–203. https://doi.org/10.1177/070674370304800308
(31) Schwarzenberg SJ, Georgieff MK. Committee on Nutrition Advocacy for improving nutrition in the first 1000 days to support childhood development and adult health Pediatrics. 2018; 141. https://DOI: 10.1542/peds.2017-3716
(32) Hashimoto M, Hossain S, Al Mamun A et al. . Docosahexaenoic acid: one molecule diverse functions. Cri Rev Biotech 2017; 37: 579-597.
https://doi: 10.1080/07388551.2016.1207153. Epub 2016 Jul 17.
(33) Mun JG, Legette LC, Ikonte CJ et al. Choline and DHA in Maternal and Infant Nutrition: Synergistic Implications in Brain and Eye Health. Nutrients 2019; 11: 1125. https://DOI: 10.3390/nu11051125
(34) Pifferi F, Roux F, Langelier B et al. (n-3) polyunsaturated fatty acid deficiency reduces the expression of both isoforms of the brain glucose transporter GLUT1 in rats. J Nutr 2005; 135: 2241-6. https://DOI: 10.1093/jn/135.9.2241
(35) Champeil-Potokar G, Chaumontet C, Guesnetp L et al. Docosahexaenoic acid (22: 6n-3) enrichment of membrane phosphor- lipids increases gap junction coupling capacity in cultured astrocytes. Eur J Neurosci 2006; 24: 3084-3090. https://doi: 10.1111/j.1460-9568.2006.05185.x.
(36) Jones CR, Arai T, Rapoport SI. Evidence for the involvement of docosahexaenoic acid in cholinergic stimulated signal transduction at the synapse. Neurochem Res. 1997; 22:663–670. https://DOI: 10.1023/a:1027341707837
(37) Rapoport SI, Ramadan E, Basselin M. Imaging plasma docosahexaenoic acid (DHA) incorporation into the brain in vivo,as a biomarker of brain DHA: Metabolism and neurotransmission. OCL 2011; 18: 246-250. https://DOI: 10.1051/ocl.2011.0396
(38) Kim HY, Spector AA, Xiong ZM. A synaptogenic amide N-docosahexaenoyl- ethanolamide promotes hippocampal development. Prostaglandins Lipid Med 2011; 96:114–120. https://doi: 10.1016/j.prostaglandins.2011.07.002
(39) Zimmer L, Hembert S, Durand G et al. Chronic n-3 polyunsaturated fatty acid diet-deficiency acts on dopamine metabolism in the rat frontal cortex: a microdialysis study. Neurosci Lett 1998; d240:177–181. https://DOI: 10.1016/s0304-3940(97)00938-5
(40) Mathieu G, Denis S, Langelier B et al. DHA enhances the noradrenaline release by SH-SY5Y cells. Neurochem Int 2010; 56:94–100.
(41) Onuki Y, Morishita M, Chiba Y et al. Docosahexaenoic acid and eicosapentae- noic acid induce changes in the physical properties of a lipid bilayer model membrane. Chem Pharm Bull 2006; 54:68–71. https://DOI: 10.1248/cpb.54.68
(42) Hashimoto M, Hossain S, Shimada T, Shido O. Docosahexaenoic acid-induced protective effect against impaired learning in amyloid beta-infused rats is associated with increased synaptosomal membrane fluidity. Clin Exp Pharmacol Physiol 2006; 33: 934–939.
(43) Bandarra NM, Lopes PA, Martins SV et al. Docosahexaenoic acid at the sn-2 position of structured triacylglycerols improved n-3 polyunsaturated fatty acid assimilation in tissues of hamsters. Nutr Res 2016; 36:452–463. https://DOI: 10.1016/j.nutres.2015.12.015 PMID: 27101763
(44) Marcheselli VL, Hong S, Lukiw WJ et al. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 2003; 278: 43807–43817. https://DOI: 10.1074/jbc.M305841200
(45) Zhao Y, Calon F, Julien C et al. Doco-sahexaenoic acid-derived neuro-protectin D1 induces neuronal survival via secretase and PPARc-mediated mechanisms in Alzheimer’s disease models. PLoS One 2011; 6: e15816. DOI: 10.1371/journal.pone.0015816
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2025/12/21
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Originalni rad / Original article