The FAAH Inhibitor URB597 Modulates Lipid Mediators in the Brain of Rats with Spontaneous Hypertension
Abstract
:1. Introduction
2. Material and Methods
2.1. Materials
2.2. Animals
2.3. Experimental Protocol
- Group 1 [WKY]: WKY rats were treated intraperitoneally (i.p.) with URB597 solvent [1 mL—mixture of DMSO, Tween 80 and saline (0.9% NaCl) [1:2:7; v:v:v]] every 12 h, during the last 14 days;
- Group 2 [WKY + URB597]: WKY rats were treated i.p. with URB597 [1 mg/kg b.w. in 1 mL of URB597 solvent] every 12 h, during the last 14 days;
- Group 3 [SHR]: SHRs were treated i.p. with URB597 solvent [1 mL] every 12 h, during the last 14 days;
- Group 4 [SHR + URB597]: SHRs were treated i.p. with URB597 [1 mg/kg b.w. in 1 mL of URB597 solvent] every 12 h, during the last 14 days.
2.4. Tissue Preparation
- The right hemisphere was pulverized in liquid nitrogen to examine levels of endocannabinoids, fatty acids and their metabolites, GSH, and FAAH activity;
- The left hemisphere after washing with isotonic saline (4 °C) was homogenized under standardized conditions to obtain 10% homogenates in 0.9% NaCl solution, which were centrifuged at 20,000× g for 15 min at 4 °C. Supernatants were used for the determination of various biochemical parameters (vitamins A and E, Cu, Zn-SOD, GSH-Px, GSSG-R, Nrf2, Keap1, Bach1, p62, HO-1, CB1, CB2, GPR55).
2.5. Methods
2.5.1. Antioxidant Enzymes Activity
2.5.2. Western Blot Analysis
2.5.3. Non-Enzymatic Antioxidants Level
2.5.4. Phospholipid and Free Fatty Acids and Their Metabolism
2.6. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Frances, A.; Sandra, O.; Lucy, U. Vascular cognitive impairment, a cardiovascular complication. World J. Psychiatry 2016, 6, 199–207. [Google Scholar] [CrossRef]
- Brito, R.; Castillo, G.; González, J.; Valls, N.; Rodrigo, R. Oxidative stress in hypertension: Mechanisms and therapeutic opportunities. Exp. Clin. Endocrinol. Diabetes Off. J. Ger. Soc. Endocrinol. Ger. Diabetes Assoc. 2015, 123, 325–335. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Di Meo, S.; Reed, T.T.; Venditti, P.; Victor, V.M. Role of ROS and RNS Sources in Physiological and Pathological Conditions. Oxid. Med. Cell. Longev. 2016, 2016, 1–44. [Google Scholar] [CrossRef] [PubMed]
- Sun, W.; Wang, X.; Hou, C.; Yang, L.; Li, H.; Guo, J.; Huo, C.; Wang, M.; Miao, Y.; Liu, J.; et al. Oleuropein improves mitochondrial function to attenuate oxidative stress by activating the Nrf2 pathway in the hypothalamic paraventricular nucleus of spontaneously hypertensive rats. Neuropharmacology 2017, 113, 556–566. [Google Scholar] [CrossRef] [PubMed]
- Figueira, L.; Israel, A. Effect of Valsartan on Cerebellar Adrenomedullin System Dysregulation during Hypertension. Cerebellum Lond. Engl. 2017, 16, 132–141. [Google Scholar] [CrossRef] [PubMed]
- Bai, J.; Yu, X.-J.; Liu, K.-L.; Wang, F.-F.; Jing, G.-X.; Li, H.-B.; Zhang, Y.; Huo, C.-J.; Li, X.; Gao, H.-L.; et al. Central administration of tert-butylhydroquinone attenuates hypertension via regulating Nrf2 signaling in the hypothalamic paraventricular nucleus of hypertensive rats. Toxicol. Appl. Pharmacol. 2017, 333, 100–109. [Google Scholar] [CrossRef]
- Dinkova-Kostova, A.T.; Abramov, A.Y. The emerging role of Nrf2 in mitochondrial function. Free Radic. Biol. Med. 2015, 88, 179–188. [Google Scholar] [CrossRef] [Green Version]
- Dyall, S.C. Long-chain omega-3 fatty acids and the brain: A review of the independent and shared effects of EPA, DPA and DHA. Front. Aging Neurosci. 2015, 7, 52. [Google Scholar] [CrossRef] [Green Version]
- Paloczi, J.; Varga, Z.V.; Hasko, G.; Pacher, P. Neuroprotection in Oxidative Stress-Related Neurodegenerative Diseases: Role of Endocannabinoid System Modulation. Antioxid. Redox Signal. 2018, 29, 75–108. [Google Scholar] [CrossRef]
- Biernacki, M.; Łuczaj, W.; Jarocka-Karpowicz, I.; Ambrożewicz, E.; Toczek, M.; Skrzydlewska, E. The Effect of Long-Term Administration of Fatty Acid Amide Hydrolase Inhibitor URB597 on Oxidative Metabolism in the Heart of Rats with Primary and Secondary Hypertension. Mol. Basel Switz. 2018, 23, 2350. [Google Scholar] [CrossRef] [Green Version]
- Biernacki, M.; Ambrożewicz, E.; Gęgotek, A.; Toczek, M.; Bielawska, K.; Skrzydlewska, E. Redox system and phospholipid metabolism in the kidney of hypertensive rats after FAAH inhibitor URB597 administration. Redox Biol. 2018, 15, 41–50. [Google Scholar] [CrossRef] [PubMed]
- Dainese, E.; Oddi, S.; Simonetti, M.; Sabatucci, A.; Angelucci, C.B.; Ballone, A.; Dufrusine, B.; Fezza, F.; De Fabritiis, G.; Maccarrone, M. Author Correction: The endocannabinoid hydrolase FAAH is an allosteric enzyme. Sci. Rep. 2020, 10, 5903. [Google Scholar] [CrossRef] [PubMed]
- Giménez, V.M.; Noriega, S.E.; Kassuha, D.E.; Fuentes, L.B.; Manucha, W. Anandamide and endocannabinoid system: An attractive therapeutic approach for cardiovascular disease. Ther. Adv. Cardiovasc. Dis. 2018, 12, 177–190. [Google Scholar] [CrossRef] [PubMed]
- Bátkai, S.; Pacher, P.; Osei-Hyiaman, D.; Radaeva, S.; Liu, J.; Harvey-White, J.; Offertáler, L.; Mackie, K.; Rudd, M.A.; Bukoski, R.D.; et al. Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. Circulation 2004, 110, 1996–2002. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Godlewski, G.; Alapafuja, S.O.; Bátkai, S.; Nikas, S.P.; Cinar, R.; Offertáler, L.; Osei-Hyiaman, D.; Liu, J.; Mukhopadhyay, B.; Harvey-White, J.; et al. Inhibitor of fatty acid amide hydrolase normalizes cardiovascular function in hypertension without adverse metabolic effects. Chem. Biol. 2010, 17, 1256–1266. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Toczek, M.; Baranowska-Kuczko, M.; Grzęda, E.; Pędzińska-Betiuk, A.; Weresa, J.; Malinowska, B. Age-specific influences of chronic administration of the fatty acid amide hydrolase inhibitor URB597 on cardiovascular parameters and organ hypertrophy in DOCA-salt hypertensive rats. Pharmacol. Rep. PR 2016, 68, 363–369. [Google Scholar] [CrossRef]
- Biernacki, M.; Ambrożewicz, E.; Gęgotek, A.; Toczek, M.; Skrzydlewska, E. Long-term administration of fatty acid amide hydrolase inhibitor (URB597) to rats with spontaneous hypertension disturbs liver redox balance and phospholipid metabolism. Adv. Med. Sci. 2018, 64, 15–23. [Google Scholar] [CrossRef]
- Ibarra-Lecue, I.; Pilar-Cuéllar, F.; Muguruza, C.; Florensa-Zanuy, E.; Díaz, Á.; Urigüen, L.; Castro, E.; Pazos, A.; Callado, L.F. The endocannabinoid system in mental disorders: Evidence from human brain studies. Biochem. Pharmacol. 2018, 157, 97–107. [Google Scholar] [CrossRef] [Green Version]
- Aso, E.; Juvés, S.; Maldonado, R.; Ferrer, I. CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AβPP/PS1 mice. J. Alzheimers Dis. JAD 2013, 35, 847–858. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Han, K.H.; Lim, S.; Ryu, J.; Lee, C.-W.; Kim, Y.; Kang, J.-H.; Kang, S.-S.; Ahn, Y.K.; Park, C.-S.; Kim, J.J. CB1 and CB2 cannabinoid receptors differentially regulate the production of reactive oxygen species by macrophages. Cardiovasc. Res. 2009, 84, 378–386. [Google Scholar] [CrossRef]
- Chung, Y.C.; Bok, E.; Huh, S.H.; Park, J.-Y.; Yoon, S.-H.; Kim, S.R.; Kim, Y.-S.; Maeng, S.; Park, S.H.; Jin, B.K. Cannabinoid receptor type 1 protects nigrostriatal dopaminergic neurons against MPTP neurotoxicity by inhibiting microglial activation. J. Immunol. 2011, 187, 6508–6517. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jia, J.; Ma, L.; Wu, M.; Zhang, L.; Zhang, X.; Zhai, Q.; Jiang, T.; Wang, Q.; Xiong, L. Anandamide protects HT22 cells exposed to hydrogen peroxide by inhibiting CB1 receptor-mediated type 2 NADPH oxidase. Oxid. Med. Cell. Longev. 2014, 2014, 1–16. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sykes, J.A.; McCormack, F.X.; O’Brien, T.J. A preliminary study of the superoxide dismutase content of some human tumors. Cancer Res. 1978, 38, 2759–2762. [Google Scholar]
- Paglia, D.E.; Valentine, W.N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 1967, 70, 158–169. [Google Scholar] [PubMed]
- Mize, C.E.; Langdon, R.G. Hepatic glutathione reductase. I. Purification and general kinetic properties. J. Biol. Chem. 1962, 237, 1589–1595. [Google Scholar] [PubMed]
- Eissa, S.; Seada, L.S. Quantitation of bcl-2 protein in bladder cancer tissue by enzyme immunoassay: Comparison with Western blot and immunohistochemistry. Clin. Chem. 1998, 44, 1423–1429. [Google Scholar] [CrossRef] [Green Version]
- Maeso, N.; García-Martínez, D.; Rupérez, F.J.; Cifuentes, A.; Barbas, C. Capillary electrophoresis of glutathione to monitor oxidative stress and response to antioxidant treatments in an animal model. J. Chromatogr. B Analyt. Technol. Biomed. Life. Sci. 2005, 822, 61–69. [Google Scholar] [CrossRef]
- Vatassery, G.T.; Brin, M.F.; Fahn, S.; Kayden, H.J.; Traber, M.G. Effect of high doses of dietary vitamin E on the concentrations of vitamin E in several brain regions, plasma, liver, and adipose tissue of rats. J. Neurochem. 1988, 51, 621–623. [Google Scholar] [CrossRef]
- Christie, W.W. Preparation of ester derivatives of fatty acids for chromatographic analysis. Adv. Lipid Methodol. 1993, 2, e111. [Google Scholar]
- Luo, X.P.; Yazdanpanah, M.; Bhooi, N.; Lehotay, D.C. Determination of aldehydes and other lipid peroxidation products in biological samples by gas chromatography-mass spectrometry. Anal. Biochem. 1995, 228, 294–298. [Google Scholar] [CrossRef]
- Coolen, S.A.J.; van Buuren, B.; Duchateau, G.; Upritchard, J.; Verhagen, H. Kinetics of biomarkers: Biological and technical validity of isoprostanes in plasma. Amino Acids 2005, 29, 429–436. [Google Scholar] [CrossRef] [PubMed]
- Lam, P.M.W.; Marczylo, T.H.; El-Talatini, M.; Finney, M.; Nallendran, V.; Taylor, A.H.; Konje, J.C. Ultra performance liquid chromatography tandem mass spectrometry method for the measurement of anandamide in human plasma. Anal. Biochem. 2008, 380, 195–201. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Siegmund, S.V.; Seki, E.; Osawa, Y.; Uchinami, H.; Cravatt, B.F.; Schwabe, R.F. Fatty acid amide hydrolase determines anandamide-induced cell death in the liver. J. Biol. Chem. 2006, 281, 10431–10438. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pawluk, H.; Pawluk, R.; Robaczewska, J.; Kędziora-Kornatowska, K.; Kędziora, J. Biomarkers of antioxidant status and lipid peroxidation in elderly patients with hypertension. Redox Rep. Commun. Free Radic. Res. 2017, 22, 542–546. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ren, J. Influence of gender on oxidative stress, lipid peroxidation, protein damage and apoptosis in hearts and brains from spontaneously hypertensive rats. Clin. Exp. Pharmacol. Physiol. 2007, 34, 432–438. [Google Scholar] [CrossRef]
- Vassallo, D.V.; Simões, M.R.; Giuberti, K.; Azevedo, B.F.; Junior, R.F.; Salaices, M.; Stefanon, I. Effects of Chronic Exposure to Mercury on Angiotensin-Converting Enzyme Activity and Oxidative Stress in Normotensive and Hypertensive Rats. Arq. Bras. Cardiol. 2019, 112, 374–380. [Google Scholar] [CrossRef]
- Cobley, J.N.; Fiorello, M.L.; Bailey, D.M. 13 reasons why the brain is susceptible to oxidative stress. Redox Biol. 2018, 15, 490–503. [Google Scholar] [CrossRef]
- Cenini, G.; Lloret, A.; Cascella, R. Oxidative Stress in Neurodegenerative Diseases: From a Mitochondrial Point of View. Oxid. Med. Cell. Longev. 2019, 2019, 1–18. [Google Scholar] [CrossRef] [Green Version]
- Nimse, S.B.; Pal, D. Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv. 2015, 5, 27986–28006. [Google Scholar] [CrossRef] [Green Version]
- Gęgotek, A.; Skrzydlewska, E. The role of transcription factor Nrf2 in skin cells metabolism. Arch. Dermatol. Res. 2015, 307, 385–396. [Google Scholar] [CrossRef] [Green Version]
- Deshmukh, P.; Unni, S.; Krishnappa, G.; Padmanabhan, B. The Keap1–Nrf2 pathway: Promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases. Biophys. Rev. 2016, 9, 41–56. [Google Scholar] [CrossRef] [PubMed]
- Waxman, E.A. Bach2 is a potent repressor of Nrf2-mediated antioxidant enzyme expression in dopaminergic neurons. BioRxiv 2019, 687590. [Google Scholar] [CrossRef]
- Kovac, S.; Angelova, P.R.; Holmström, K.M.; Zhang, Y.; Dinkova-Kostova, A.T.; Abramov, A.Y. Nrf2 regulates ROS production by mitochondria and NADPH oxidase. Biochim. Biophys. Acta 2015, 1850, 794–801. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dyall, S.C. Interplay between n-3 and n-6 Long-Chain Polyunsaturated Fatty Acids and the Endocannabinoid System in Brain Protection and Repair. Lipids 2017, 52, 885–900. [Google Scholar] [CrossRef]
- Layé, S.; Nadjar, A.; Joffre, C.; Bazinet, R.P. Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology. Pharmacol. Rev. 2018, 70, 12–38. [Google Scholar] [CrossRef]
- Parchem, K.; Sasson, S.; Ferreri, C.; Bartoszek, A. Qualitative analysis of phospholipids and their oxidised derivatives—Used techniques and examples of their applications related to lipidomic research and food analysis. Free Radic. Res. 2019, 53, 1068–1100. [Google Scholar] [CrossRef]
- Taso, O.V.; Philippou, A.; Moustogiannis, A.; Zevolis, E.; Koutsilieris, M. Lipid peroxidation products and their role in neurodegenerative diseases. Ann. Res. Hosp. 2019, 3, 2. [Google Scholar] [CrossRef]
- Ahmad, A.; Singhal, U.; Hossain, M.M.; Islam, N.; Rizvi, I. The role of the endogenous antioxidant enzymes and malondialdehyde in essential hypertension. J. Clin. Diagn. Res. JCDR 2013, 7, 987–990. [Google Scholar] [CrossRef]
- Li, H.; Liu, X.; Ren, Z.; Gu, J.; Lu, Y.; Wang, X.; Zhang, L. Effects of Diabetic Hyperglycemia on Central Ang-(1-7)-Mas-R-nNOS Pathways in Spontaneously Hypertensive Rats. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 2016, 40, 1186–1197. [Google Scholar] [CrossRef]
- Yavuzer, H.; Yavuzer, S.; Cengiz, M.; Erman, H.; Doventas, A.; Balci, H.; Erdincler, D.S.; Uzun, H. Biomarkers of lipid peroxidation related to hypertension in aging. Hypertens. Res. Off. J. Jpn. Soc. Hypertens. 2016, 39, 342–348. [Google Scholar] [CrossRef]
- Adibhatla, R.M.; Hatcher, J.F. Secretory phospholipase a2 iia is up-regulated by tnf-α and il-1α/β after transient focal cerebral ischemia in rat. Brain Res. 2007, 1134, 199–205. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Das, U.N. Arachidonic acid in health and disease with focus on hypertension and diabetes mellitus: A review. J. Adv. Res. 2018, 11, 43–55. [Google Scholar] [CrossRef] [PubMed]
- Bouchard, J.-F.; Casanova, C.; Cécyre, B.; Redmond, W.J. Expression and Function of the Endocannabinoid System in the Retina and the Visual Brain. Neural Plast. 2016, 2016, 1–14. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Freund, T.F.; Katona, I.; Piomelli, D. Role of endogenous cannabinoids in synaptic signaling. Physiol. Rev. 2003, 83, 1017–1066. [Google Scholar] [CrossRef]
- Kim, M.J.; Tanioka, M.; Woo Um, S.; Hong, S.-K.; Lee, B.H. Analgesic effects of FAAH inhibitor in the insular cortex of nerve-injured rats. Mol. Pain 2018, 14, 14. [Google Scholar]
- Balenga, N.A.B.; Aflaki, E.; Kargl, J.; Platzer, W.; Schröder, R.; Blättermann, S.; Kostenis, E.; Brown, A.J.; Heinemann, A.; Waldhoer, M. GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils. Cell Res. 2011, 21, 1452–1469. [Google Scholar] [CrossRef] [Green Version]
- Moreno, E.; Andradas, C.; Medrano, M.; Caffarel, M.M.; Pérez-Gómez, E.; Blasco-Benito, S.; Gómez-Cañas, M.; Pazos, M.R.; Irving, A.J.; Lluís, C.; et al. Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling. J. Biol. Chem. 2014, 289, 21960–21972. [Google Scholar] [CrossRef] [Green Version]
- Hoffman, A.F.; Laaris, N.; Kawamura, M.; Masino, S.A.; Lupica, C.R. Control of cannabinoid CB1 receptor function on glutamate axon terminals by endogenous adenosine acting at A1 receptors. J. Neurosci. Off. J. Soc. Neurosci. 2010, 30, 545–555. [Google Scholar] [CrossRef]
- Li, H.; Wood, J.T.; Whitten, K.M.; Vadivel, S.K.; Seng, S.; Makriyannis, A.; Avraham, H.K. Inhibition of fatty acid amide hydrolase activates Nrf2 signalling and induces heme oxygenase 1 transcription in breast cancer cells. Br. J. Pharmacol. 2013, 170, 489–505. [Google Scholar] [CrossRef] [Green Version]
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Biernacki, M.; Baranowska-Kuczko, M.; Niklińska, G.N.; Skrzydlewska, E. The FAAH Inhibitor URB597 Modulates Lipid Mediators in the Brain of Rats with Spontaneous Hypertension. Biomolecules 2020, 10, 1022. https://doi.org/10.3390/biom10071022
Biernacki M, Baranowska-Kuczko M, Niklińska GN, Skrzydlewska E. The FAAH Inhibitor URB597 Modulates Lipid Mediators in the Brain of Rats with Spontaneous Hypertension. Biomolecules. 2020; 10(7):1022. https://doi.org/10.3390/biom10071022
Chicago/Turabian StyleBiernacki, Michał, Marta Baranowska-Kuczko, Gabriella N. Niklińska, and Elżbieta Skrzydlewska. 2020. "The FAAH Inhibitor URB597 Modulates Lipid Mediators in the Brain of Rats with Spontaneous Hypertension" Biomolecules 10, no. 7: 1022. https://doi.org/10.3390/biom10071022