Effects of erythropoietin on bile duct ligation-induced neuro-inflammation in male rats

Moazameh Golshani; Mohsen Basiri; Mohammad Shabani; Iraj Aghaei; Majid Asadi-Shekaari; Moazameh Golshani; Mohsen Basiri; Mohammad Shabani; Iraj Aghaei; Majid Asadi-Shekaari

doi:10.3934/Neuroscience.2019.2.43

AIMS Neuroscience

2019, Volume 6, Issue 2: 43-53. doi: 10.3934/Neuroscience.2019.2.43

Previous Article Next Article

Research article

Effects of erythropoietin on bile duct ligation-induced neuro-inflammation in male rats

1.
Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
2.
Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran
3.
Neuroscience Research Center, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran

Received: 24 December 2018 Accepted: 18 March 2019 Published: 29 April 2019

Hepatic encephalopathy (HE) is a brain disorder as a result of liver failure. Previous studies have indicated that erythropoietin (EPO) has neuroprotective effects in different neurological diseases. This study addressed the therapeutic effect of a four-week treatment with EPO on neuronal damages in bile duct-ligated rats. Forty male Wistar rats (250–280 g) were used in the present study. The animals were randomly divided into four groups consisting of 10 animals each, including sham, sham + EPO, bile duct ligation (BDL), and BDL + EPO. EPO was intraperitoneally administered every other day (5,000 U/Kg) in the last four weeks after BDL. Biochemical and histological studies were performed to evaluate neurodegeneration. The results revealed that BDL increases the level of hepatic enzymes and total bilirubin. Furthermore, neurodegeneration was significantly increased in the BDL group compared to sham groups. EPO preserved hepatic enzymes and total bilirubin in the treated group. In addition, EPO significantly decreased the neurodegeneration in BDL + EPO compared to the BDL group. Results of this study showed that EPO has neuroprotective effects in the rat model of HE, possibly due to its anti-inflammatory and anti-oxidant properties. Complementary studies are required to clarify the exact mechanisms.
- bile duct ligation,
- hepatic encephalopathy,
- erythropoietin,
- astrocytes,
- microglia
Citation: Moazameh Golshani, Mohsen Basiri, Mohammad Shabani, Iraj Aghaei, Majid Asadi-Shekaari. Effects of erythropoietin on bile duct ligation-induced neuro-inflammation in male rats[J]. AIMS Neuroscience, 2019, 6(2): 43-53. doi: 10.3934/Neuroscience.2019.2.43

Related Papers:

Abstract

Hepatic encephalopathy (HE) is a brain disorder as a result of liver failure. Previous studies have indicated that erythropoietin (EPO) has neuroprotective effects in different neurological diseases. This study addressed the therapeutic effect of a four-week treatment with EPO on neuronal damages in bile duct-ligated rats. Forty male Wistar rats (250–280 g) were used in the present study. The animals were randomly divided into four groups consisting of 10 animals each, including sham, sham + EPO, bile duct ligation (BDL), and BDL + EPO. EPO was intraperitoneally administered every other day (5,000 U/Kg) in the last four weeks after BDL. Biochemical and histological studies were performed to evaluate neurodegeneration. The results revealed that BDL increases the level of hepatic enzymes and total bilirubin. Furthermore, neurodegeneration was significantly increased in the BDL group compared to sham groups. EPO preserved hepatic enzymes and total bilirubin in the treated group. In addition, EPO significantly decreased the neurodegeneration in BDL + EPO compared to the BDL group. Results of this study showed that EPO has neuroprotective effects in the rat model of HE, possibly due to its anti-inflammatory and anti-oxidant properties. Complementary studies are required to clarify the exact mechanisms.

Acknowledgments

This research was supported by the Neuroscience Research Center of Kerman University of Medical Sciences. The data presented in this scientific paper are taken from Moazameh Golshani's MSc thesis.

Conflict of interest

The authors declare no conflict of interest.

References

[1]	Felipo V (2013) Hepatic encephalopathy: effects of liver failure on brain function. Nat Rev Neurosci 14: 851–858. doi: 10.1038/nrn3587
[2]	Olde Damink SW, Jalan R, Dejong CH (2009) Interorgan ammonia trafficking in liver disease. Metab Brain Dis 24: 169–181. doi: 10.1007/s11011-008-9122-5
[3]	Butterworth RF, Norenberg MD, Felipo V, et al. (2009) Experimental models of hepatic encephalopathy: ISHEN guidelines. Liver Int 29: 783–788. doi: 10.1111/j.1478-3231.2009.02034.x
[4]	Leke R, Oliveira DL, Forgiarini LF, et al. (2013) Impairment of short term memory in rats with hepatic encephalopathy due to bile duct ligation. Metab Brain Dis 28: 187–192. doi: 10.1007/s11011-012-9347-1
[5]	Weissenborn K, Giewekemeyer K, Heidenreich S, et al. (2005) Attention, memory, and cognitive function in hepatic encephalopathy. Metab Brain Dis 20: 359–367. doi: 10.1007/s11011-005-7919-z
[6]	Ferenci P, Lockwood A, Mullen K, et al. (2002) Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology 35: 716–721. doi: 10.1053/jhep.2002.31250
[7]	Patel A, Wade JB, Thacker LR, et al. (2014) 991 Brain Reserve Modulates Health-Related Quality of Life in Patients With Cirrhosis Independent of Covert Hepatic Encephalopathy and MELD Score. Gastroenterology 146: S–932.
[8]	Rose CF (2012) Ammonia-lowering strategies for the treatment of hepatic encephalopathy. Clin Pharmacol Ther 92: 321–331. doi: 10.1038/clpt.2012.112
[9]	Savlan I, Liakina V, Valantinas J (2014) Concise review of current concepts on nomenclature and pathophysiology of hepatic encephalopathy. Medicina (Kaunas) 50: 75–81. doi: 10.1016/j.medici.2014.06.008
[10]	Rama Rao KV, Jayakumar AR, Norenberg MD (2012) Glutamine in the pathogenesis of acute hepatic encephalopathy. Neurochem Int 61: 575–580. doi: 10.1016/j.neuint.2012.01.012
[11]	Rothman DL, De Feyter HM, Maciejewski PK, et al. (2012) Is there in vivo evidence for amino acid shuttles carrying ammonia from neurons to astrocytes? Neurochem Res 37: 2597–2612. doi: 10.1007/s11064-012-0898-7
[12]	Jover R, Rodrigo R, Felipo V, et al. (2006) Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis. Hepatology 43: 1257–1266. doi: 10.1002/hep.21180
[13]	Sheen JM, Huang LT, Hsieh CS, et al. (2010) Bile duct ligation in developing rats: temporal progression of liver, kidney, and brain damage. J Pediatr Surg 45: 1650–1658. doi: 10.1016/j.jpedsurg.2009.12.019
[14]	Aldridge DR, Tranah EJ, Shawcross DL (2015) Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation. J Clin Exp Hepatol 5: S7–S20.
[15]	Rodrigo R, Cauli O, Gomez-Pinedo U, et al. (2010) Hyperammonemia induces neuroinflammation that contributes to cognitive impairment in rats with hepatic encephalopathy. Gastroenterology 139: 675–684. doi: 10.1053/j.gastro.2010.03.040
[16]	Jayakumar AR, Rama Rao KV, Norenberg MD (2015) Neuroinflammation in hepatic encephalopathy: mechanistic aspects. J Clin Exp Hepatol 5: S21–28.
[17]	Butterworth RF (2012) Reprint of: Neuroinflammation in acute liver failure: Mechanisms and novel therapeutic targets. Neurochem Int 60: 715–722. doi: 10.1016/j.neuint.2012.03.014
[18]	Aghaei I, Nazeri M, Shabani M, et al. (2015) Erythropoietin ameliorates the motor and cognitive function impairments in a rat model of hepatic cirrhosis. Metab Brain Dis 30: 197–204. doi: 10.1007/s11011-014-9600-x
[19]	Aghaei I, Shabani M, Doustar N, et al. (2014) Peroxisome proliferator-activated receptor-gamma activation attenuates motor and cognition impairments induced by bile duct ligation in a rat model of hepatic cirrhosis. Pharmacol Biochem Behav 120: 133–139. doi: 10.1016/j.pbb.2014.03.002
[20]	Nairz M, Schroll A, Moschen AR, et al. (2011) Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting nuclear factor-kappaB-inducible immune pathways. Immunity 34: 61–74. doi: 10.1016/j.immuni.2011.01.002
[21]	Bond WS, Rex TS (2014) Evidence that erythropoietin modulates neuroinflammation through differential action on neurons, astrocytes, and microglia. Front Immunol 5: 523.
[22]	Aghaei I, Hajali V, Dehpour A, et al. (2016) Alterations in the intrinsic electrophysiological properties of Purkinje neurons in a rat model of hepatic encephalopathy: Relative preventing effect of PPARgamma agonist. Brain Res Bull 121: 16–25. doi: 10.1016/j.brainresbull.2015.12.002
[23]	Shabani M, Ebrahimpoor F, Firouzjaei MA, et al. (2019) Modulation of sphingosine-1-phosphate receptor by FTY720 contributes in improvement of hepatic encephalopathy induced by bile duct ligation. Brain Res Bull 146: 253–269. doi: 10.1016/j.brainresbull.2019.01.012
[24]	Tahamtan M, Aghaei I, Pooladvand V, et al. (2017) Characterization of the CA1 pyramidal neurons in rat model of hepatic cirrhosis: insights into their electrophysiological properties. Metab Brain Dis 32: 881–889. doi: 10.1007/s11011-017-9966-7
[25]	Onoda A, Takeda K, Umezawa M (2017) Dose-dependent induction of astrocyte activation and reactive astrogliosis in mouse brain following maternal exposure to carbon black nanoparticle. Part Fibre Toxicol 14: 4. doi: 10.1186/s12989-017-0184-6
[26]	Matsui H, Ohgomori T, Natori T, et al. (2013) Keratan sulfate expression in microglia is diminished in the spinal cord in experimental autoimmune neuritis. Cell Death Dis 4: e946. doi: 10.1038/cddis.2013.479
[27]	Javadi-Paydar M, Ghiassy B, Ebadian S, et al. (2013) Nitric oxide mediates the beneficial effect of chronic naltrexone on cholestasis-induced memory impairment in male rats. Behav Pharmacol 24: 195–206. doi: 10.1097/FBP.0b013e3283618a8c
[28]	Nasehi M, Piri M, Abbolhasani K, et al. (2013) Involvement of opioidergic and nitrergic systems in memory acquisition and exploratory behaviors in cholestatic mice. Behav Pharmacol 24: 180–194. doi: 10.1097/FBP.0b013e3283618aab
[29]	Butterworth RF (2011) Hepatic encephalopathy: a central neuroinflammatory disorder? Hepatology 53: 1372–1376. doi: 10.1002/hep.24228
[30]	Huang LT, Tiao MM, Tain YL, et al. (2009) Melatonin ameliorates bile duct ligation-induced systemic oxidative stress and spatial memory deficits in developing rats. Pediatr Res 65: 176–180. doi: 10.1203/PDR.0b013e31818d5bc7
[31]	Brines M, Cerami A (2005) Emerging biological roles for erythropoietin in the nervous system. Nat Rev Neurosci 6: 484–494. doi: 10.1038/nrn1687
[32]	Levitt DG, Levitt MD (2016) Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements. Int J Gen Med 9: 229–255. doi: 10.2147/IJGM.S102819
[33]	Caillaud C, Mechta M, Ainge H, et al. (2015) Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats. J Endocrinol 225: 77–88. doi: 10.1530/JOE-15-0010
[34]	Dhanda S, Sandhir R (2015) Role of dopaminergic and serotonergic neurotransmitters in behavioral alterations observed in rodent model of hepatic encephalopathy. Behav Brain Res 286: 222–235. doi: 10.1016/j.bbr.2015.01.042
[35]	Su YY, Yang GF, Lu GM, et al. (2015) PET and MR imaging of neuroinflammation in hepatic encephalopathy. Metab Brain Dis 30: 31–45. doi: 10.1007/s11011-014-9633-1
[36]	Chen JR, Wang BN, Tseng GF, et al. (2014) Morphological changes of cortical pyramidal neurons in hepatic encephalopathy. BMC Neurosci 15: 15. doi: 10.1186/1471-2202-15-15
[37]	Ponce LL, Navarro JC, Ahmed O, et al. (2013) Erythropoietin neuroprotection with traumatic brain injury. Pathophysiology 20: 31–38. doi: 10.1016/j.pathophys.2012.02.005
[38]	Wenker SD, Chamorro ME, Vittori DC, et al. (2013) Protective action of erythropoietin on neuronal damage induced by activated microglia. FEBS J 280: 1630–1642. doi: 10.1111/febs.12172
[39]	McPherson RJ, Juul SE (2008) Recent trends in erythropoietin-mediated neuroprotection. Int J Dev Neurosci 26: 103–111. doi: 10.1016/j.ijdevneu.2007.08.012
[40]	Mofidi A, Bader A, Pavlica S (2011) The use of erythropoietin and its derivatives to treat spinal cord injury. Mini Rev Med Chem 11: 763–770. doi: 10.2174/138955711796355267
[41]	Hu X, Liou AK, Leak RK, et al. (2014) Neurobiology of microglial action in CNS injuries: receptor-mediated signaling mechanisms and functional roles. Prog Neurobiol 119–120: 60–84.
[42]	Wright G, Swain M, Annane D, et al. (2016) Neuroinflammation in liver disease: sessional talks from ISHEN. Metab Brain Dis 31: 1339–1354. doi: 10.1007/s11011-016-9918-7

Reader Comments

Your name:*

Email:*
© 2019 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)