Mesoporous silica SBA-15 decreases hyperammonemia and affects the gene expression of mitogen-activated protein kinases in the prefrontal cortex of rats with bile duct ligation

Document Type: Original Article

Authors

1 Department of Biological Science, Faculty of Science, University of Kurdistan, Sanandaj, Iran

2 Department of Chemistry, Faculty of Science, University of Kurdistan, Sanandaj, Iran

10.22038/ijbms.2020.44658.10436

Abstract

Objective(s): We aim to examine possible ammonia lowering effects of mesoporous silica SBA-15 in rats after the common bile duct ligation (BDL). We also evaluate the effect of SBA-15 treatments during 28 days of BDL on locomotion and rearing behavior, as well as on the gene expression of Jnk3 and p38alpha (p38α) mitogen-activated protein kinases in the prefrontal cortex (PFC).
Materials and Methods: SBA-15 was prepared with the hydrothermal method from the surfactant P123 and tetraethyl orthosilicate (TEOS), and calcined at 550 ºC. Then, the product was characterized by FT-IR, XRD, SEM, and BJH-BET techniques. Male Wistar rats in sham control and a group with BDL received saline but another group with BDL received SBA-15 during 28 days of BDL. We examined all groups of rats weekly for locomotion and rearing behavior; then on day 28, we sacrificed all rats, collected the blood sample, and finally dissected the PFC from the whole brain.
Results: The SBA-15 treatments had no effect on locomotion but improved rearing behavior on days 7 and 14 of BDL. Biochemical analysis indicated that the SBA-15 treatments in rats with BDL significantly decreased hyperammonemia. The results also revealed that the SBA-15 treatments in rats with BDL significantly restored the decreased Jnk3 gene expression, and increased the p38α gene expression in the PFC.
Conclusion: We conclude that SBA-15 can be used as an ammonia lowering agent in hepatic encephalopathy; however, its improving effects on locomotion and neuroinflammation, as well as signaling molecules in the brain need more investigations.

Keywords


1. Liu J, Lkhagva E, Chung HJ, Kim HJ, Hong ST. The pharmabiotic approach to treat hyperammonemia. Nutrients 2018; 10:E140.
2. Matoori S, Leroux JC. Recent advances in the treatment of hyperammonemia. Adv Drug Deliv Rev 2015; 90:55-68.
3. Thomsen KL, De Chiara F, Rombouts K, Vilstrup H, Andreola F, Mookerjee RP, et al. Ammonia: A novel target for the treatment of non-alcoholic steatohepatitis. Med Hypotheses 2018; 113:91-97.
4. Felipo V. Hepatic encephalopathy: effects of liver failure on brain function. Nat Rev Neurosci 2013; 14:851-858.
5. Parekh PJ, Balart LA. Ammonia and its role in the pathogenesis of hepatic encephalopathy. Clin Liver Dis 2015; 19:529-537.
6. Butterworth RF. Pathogenesis of hepatic encephalopathy in cirrhosis: the concept of synergism revisited. Metab Brain Dis 2016; 31:1211-1215.
7. Rodrigo R, Cauli O, Gomez-Pinedo U, Agusti A, Hernandez-Rabaza V, Garcia-Verdugo JM, et al. Hyperammonemia induces neuroinflammation that contributes to cognitive impairment in rats with hepatic encephalopathy. Gastroenterology 2010; 139:675-684.
8. Jayakumar AR, Rama Rao KV, Norenberg MD. Neuroinflammation in hepatic encephalopathy: mechanistic aspects. J Clin Exp Hepatol 2015; 5:S21-28.
9. Zemtsova I, Gorg B, Keitel V, Bidmon HJ, Schror K, Haussinger D. Microglia activation in hepatic encephalopathy in rats and humans. Hepatology 2011; 54:204-215.
10. Prakash R, Mullen KD. Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol 2010; 7:515-525.
11. Sorensen M. Update on cerebral uptake of blood ammonia. Metab Brain Dis 2013; 28:155-159.
12. Khaledi S, Ahmadi S. Hepatic encephalopathy: pathogenesis and treatment strategies. Shefaye Khatam 2019; 7:77-90.
13. Soria LR, Brunetti-Pierri N. Targeting autophagy for therapy of hyperammonemia. Autophagy 2018; 14:1273-1275.
14. Wang Y, Zhao Q, Han N, Bai L, Li J, Liu J, et al. Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomedicine 2015; 11:313-327.
15. Jafari S, Derakhshankhah H, Alaei L, Fattahi A, Varnamkhasti BS, Saboury AA. Mesoporous silica nanoparticles for therapeutic/diagnostic applications. Biomed Pharmacother 2019; 109:1100-1111.
16. Siefker J, Karande P, Coppens MO. Packaging biological cargoes in mesoporous materials: opportunities for drug delivery. Expert Opin Drug Deliv 2014; 11:1781-1793.
17. Song C, Wang X, Wang Y, Yu H, Cui Y, Ma T. Advances in the use of multifunctional mesoporous silica nanoparticles and related nanomaterials as carriers for the cancer treatment. Curr Drug Metab 2018; 19:131-141.
18. Yang Y, Yu C. Advances in silica based nanoparticles for targeted cancer therapy. Nanomedicine 2016; 12:317-332.
19. Scaramuzzi K, Tanaka GD, Neto FM, Garcia PR, Gabrili JJ, Oliveira DC, et al. Nanostructured SBA-15 silica: an effective protective vehicle to oral hepatitis B vaccine immunization. Nanomedicine 2016; 12:2241-2250.
20. Butterworth RF, Norenberg MD, Felipo V, Ferenci P, Albrecht J, Blei AT. Experimental models of hepatic encephalopathy: ISHEN guidelines. Liver Int 2009; 29:783-788.
21. Ahmadi S, Poureidi M, Rostamzadeh J. Hepatic encephalopathy induces site-specific changes in gene expression of GluN1 subunit of NMDA receptor in rat brain. Metab Brain Dis 2015; 30:1035-1041.
22. Agusti A, Cauli O, Rodrigo R, Llansola M, Hernandez-Rabaza V, Felipo V. p38 MAP kinase is a therapeutic target for hepatic encephalopathy in rats with portacaval shunts. Gut 2011; 60:1572-1579.
23. Guo XX, An S, Yang Y, Liu Y, Hao Q, Tang T, et al. Emerging role of the Jun N-terminal kinase interactome in human health. Cell Biol Int 2018; 42:756-768.
24. Felipo V, Piedrafita B, Barios JA, Agusti A, Ahabrach H, Romero-Vives M, et al. Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations. Chronobiol Int 2015; 32:966-979.
25. Bachstetter AD, Van Eldik LJ. The p38 MAP kinase family as regulators of proinflammatory cytokine production in degenerative diseases of the CNS. Aging Dis 2010; 1:199-211.
26. Waetzig V, Czeloth K, Hidding U, Mielke K, Kanzow M, Brecht S, et al. c-Jun N-terminal kinases (JNKs) mediate pro-inflammatory actions of microglia. Glia 2005; 50:235-246.
27. Coffey ET. Nuclear and cytosolic JNK signalling in neurons. Nat Rev Neurosci 2014; 15:285-299.
28. Moriyama M, Jayakumar AR, Tong XY, Norenberg MD. Role of mitogen-activated protein kinases in the mechanism of oxidant-induced cell swelling in cultured astrocytes. J Neurosci Res 2010; 88:2450-2458.
29. Panickar KS, Jayakumar AR, Rao KV, Norenberg MD. Ammonia-induced activation of p53 in cultured astrocytes: role in cell swelling and glutamate uptake. Neurochem Int 2009; 55:98-105.
30. Jayakumar AR, Panickar KS, Murthy Ch R, Norenberg MD. Oxidative stress and mitogen-activated protein kinase phosphorylation mediate ammonia-induced cell swelling and glutamate uptake inhibition in cultured astrocytes. J Neurosci 2006; 26:4774-4784.
31. Irie T, Miyamoto E, Kitagawa K, Maruyama Y, Inoue K, Inagaki C. An anxiolytic agent, dihydrohonokiol-B, inhibits ammonia-induced increases in the intracellular Cl(-) of cultured rat hippocampal neurons via GABA(c) receptors. Neurosci Lett 2001; 312:121-123.
32. Malaguarnera M, Llansola M, Balzano T, Gómez-Giménez B, Antúnez-Muñoz C, Martínez-Alarcón N, et al. Bicuculline reduces neuroinflammation in hippocampus and improves spatial learning and anxiety in hyperammonemic rats. Role of glutamate receptors. Front Pharmacol 2019; 10:132-145.
33. Llansola M, Montoliu C, Cauli O, Hernandez-Rabaza V, Agusti A, Cabrera-Pastor A, et al. Chronic hyperammonemia, glutamatergic neurotransmission and neurological alterations. Metab Brain Dis 2013; 28:151-154.
34. Ahmadi S, Faridi S, Tahmasebi S. Calcium-dependent kinases in the brain have site-specific associations with locomotion and rearing impairments in rats with bile duct ligation. Behav Brain Res 2019; 372:112009.
35. Ahmadi S, Karami Z, Mohammadian A, Khosrobakhsh F, Rostamzadeh J. Cholestasis induced antinociception and decreased gene expression of MOR1 in rat brain. Neuroscience 2015; 284:78-86.
36. Samadi S, Ashouri A, Ghambarian M. Use of CuO encapsulated in mesoporous silica SBA-15 as a recycled catalyst for allylic C–H bond oxidation of cyclic olefins at room temperature. RSC Adv 2017; 7:19330-19337.
37. Zhao D, Feng J, Huo Q, Melosh N, Fredrickson GH, Chmelka BF, et al. Triblock copolymer syntheses of mesoporous silica with periodic 50 to 300 angstrom pores. Science 1998; 279:548-552.
38. Hudson SP, Padera RF, Langer R, Kohane DS. The biocompatibility of mesoporous silicates. Biomaterials 2008; 29:4045-4055.
39. Choi Y, Lee JE, Lee JH, Jeong JH, Kim J. A biodegradation study of SBA-15 microparticles in simulated body fluid and in vivo. Langmuir 2015; 31:6457-6462.
40. Ahmadi S, Khaledi S. Anxiety in rats with bile duct ligation is associated with activation of JNK3 mitogen-activated protein kinase in the hippocampus. Metab Brain Dis 2020; 35:579-588.
41. Samadi S, Ashouri A, Ghambarian M. Use of CuO encapsulated in mesoporous silica SBA-15 as a recycled catalyst for allylic C–H bond oxidation of cyclic olefins at room temperature. RSC Advances 2017; 7:19330-19337.
42. Samadi S, Jadidi K, Khanmohammadi B, Tavakoli N. Heterogenization of chiral mono oxazoline ligands by grafting onto mesoporous silica MCM-41 and their application in copper-catalyzed asymmetric allylic oxidation of cyclic olefins. J Catal 2016; 340:344-353.
43. Li Y, Sun N, Li L, Zhao N, Xiao F, Wei W, et al. Grafting of amines on ethanol-extracted SBA-15 for CO2 adsorption. Materials 2013; 6:981-999.
44. Giraldo L, Moreno-Piraján JC. Calorimetric study of mesoporous SBA-15 modified for controlled valproic acid delivery. J Chem 2013; 2013:1-11.
45. Gao D, Duan A, Zhang X, Chi K, Zhao Z, Li J, et al. Self-assembly of monodispersed hierarchically porous Beta-SBA-15 with different morphologies and its hydro-upgrading performances for FCC gasoline. J Mater Chem A 2015; 3:16501-16512.
46. Kosuge K, Sato T, Kikukawa N, Takemori M. Morphological control of rod-and fiberlike SBA-15 type mesoporous silica using water-soluble sodium silicate. Chem Mater 2004; 16:899-905.
47. Chen C, Zheng H, Xu J, Shi X, Li F, Wang X. Sustained-release study on exenatide loaded into mesoporous silica nanoparticles: in vitro characterization and in vivo evaluation. Daru 2017; 25:20-27.
48. Jiang F, Liu Y, Wang X, Yin Z. pH-sensitive release of insulin-loaded mesoporous silica particles and its coordination mechanism. Eur J Pharm Sci 2018; 119:1-12.
49. Cauli O, Mansouri MT, Agusti A, Felipo V. Hyperammonemia increases GABAergic tone in the cerebellum but decreases it in the rat cortex. Gastroenterology 2009; 136:1359-1367, e1351-1352.
50. Aldridge DR, Tranah EJ, Shawcross DL. Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation. J Clin Exp Hepatol 2015; 5:S7-S20.
51. Bosoi CR, Rose CF. Oxidative stress: a systemic factor implicated in the pathogenesis of hepatic encephalopathy. Metab Brain Dis 2013; 28:175-178.
52. Coltart I, Tranah TH, Shawcross DL. Inflammation and hepatic encephalopathy. Arch Biochem Biophys 2013; 536:189-196.
53. Gorg B, Schliess F, Haussinger D. Osmotic and oxidative/nitrosative stress in ammonia toxicity and hepatic encephalopathy. Arch Biochem Biophys 2013; 536:158-163.
54. Jiang X, Xu L, Tang L, Liu F, Chen Z, Zhang J, et al. Role of the indoleamine-2,3-dioxygenase/kynurenine pathway of tryptophan metabolism in behavioral alterations in a hepatic encephalopathy rat model. J Neuroinflammation 2018; 15:3-18.
55. Shawcross DL, Davies NA, Williams R, Jalan R. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol 2004; 40:247-254.
56. Rose CF. Ammonia-lowering strategies for the treatment of hepatic encephalopathy. Clin Pharmacol Ther 2012; 92:321-331.
57. Avruch J. MAP kinase pathways: the first twenty years. Biochim Biophys Acta 2007; 1773:1150-1160.
58. Kumagae Y, Zhang Y, Kim OJ, Miller CA. Human c-Jun N-terminal kinase expression and activation in the nervous system. Brain Res Mol Brain Res 1999; 67:10-17.
59. Cauli O, Rodrigo R, Piedrafita B, Boix J, Felipo V. Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatology 2007; 46:514-519.