THE POSSIBLE EFFECTS OF SILYMARIN ON CEREBRUM WITH EXPERIMENTAL HEPATIC ENCEPHALOPATHY IN RATS
Background: The relationship between liver diseases and neurological defects is well established. Hepatic encephalopathy (HE) has been seen both in people with acute liver failure (ALF) and chronic liver disease (CLF). HE is a complex neuropsychiatric syndrome that is seen in patients suffering from liver dysfunction. Silymarin (Sm) has antioxidant, anti-inflammatory, and anti-carcinogenic features. In this study, the possible protective effects of silymarin were investigated against dorsolateral prefrontal cortex (DLPFC) damage induced by thioacetamide (TAA).
Method: To achieve this, male Sprague Dawley rats (200-250 g) were randomly divided into four groups, with 7 animals comprising each group: the control group, 50 mg/kg TAA group, 50 mg/kg Sm + TAA group, and 100 mg / kg Sm + TAA group.
Results: Differences between the groups were determined by performing immunohistochemical analysis of the PFC. Bax, TNF-α, and TUNEL expression increased in the brain tissue of the experimental group where only TAA was administered.
Conclusions: It was observed that in high doses in particular (100 mg/kg Sm + TAA group), Sm was effective in preventing PFC damage caused by TAA. It was determined that 100 mg/kg Sm significantly reduces TAA-induced inflammation (TNF-α and H&E) and apoptosis (Bax, TUNEL) in brain tissue.
Felipo V: Hepatic encephalopathy: effects of liver failure on brain function in Nat Rev Neurosci. (2013) 14(12):851-8. DOI: https://doi.org/10.1038/nrn3587
Butterworth RF, Norenberg MD, Felipo V, Ferenci P, Albrecht J, and Blei AT Experimental models of hepatic encephalopathy: ISHEN guidelines. Liver Int. (2009) 29(6):783-8. DOI: https://doi.org/10.1111/j.1478-3231.2009.02034.x
Dyroff MC and Neal RA: Studies of the mechanism of metabolism of thioacetamide S-oxide by rat liver microsomes in Mol Pharmacol. (1983) 233:219–227.
Hunter AL, Holscher MA, and Neal RA. Thioacetamide-induced hepatic necrosis. I. Involvement of the mixed-function oxidase enzyme system in J Pharmacol Exp Therap. (1977) 200:439-448.
Sarma D, Hajovsky H, Koen YM, Galeva NA, Williams TD, Staudinger JL, and Hanzlik RP: Covalent modification of lipids and proteins in rat hepatocytes, and in vitro, by thioacetamide metabolites in Chem Res Toxicol. (2012) 17;25(9):1868-77. DOI: https://doi.org/10.1021/tx3001658
Arnould-Taylor W: A Textbook of Anatomy and Physiology. Nelson Thornes, (2015).
Rao KV and Norenberg MD: Cerebral energy metabolism in hepatic encephalopathy and hyperammonemia in Metab Brain Dis. (2001) 16(1-2):67-78. DOI: https://doi.org/10.1023/A:1011666612822
Lockwood AH, Yap EW and Wong WH: Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy inJ Cereb Blood Flow Metab:(1991) 11(2):337-41. DOI: https://doi.org/10.1038/jcbfm.1991.67
Kumar G, Taneja A and Kandiah PA: Brain and the Liver: Cerebral Edema, Hepatic Encephalopathy and Beyond in hepatic Critical Care. (2020) 83-103.
Liu G, Wang T, Wang T, Song J, and Zhou Z. Effects of apoptosis-related proteins caspase 3, Bax and Bcl 2 on cerebral ischemia rats in Biomed. Rep. (2013) 1:861-867. DOI: https://doi.org/10.3892/br.2013.153
Elisabeth M, Steven W, and Kim Grahatle: The Evolution of Memory Systems: Ancestors, Anatomy, and Adaptations. Oxford University Press. Oxford. (2016) pp: 22–24.
Cengiz, M., Kutlu, HM, Burukoglu, DD, & Ayhancı, A. (2015). A comparative study on therapeutic effects of silymarin and silymarin-loaded solid lipid nanoparticles on D -GaIN / TNF-α-induced liver damage in Balb / c mice. Food and Chemical Toxicology, 77, 93-100. DOI: https://doi.org/10.1016/j.fct.2014.12.011
Gabrieli JD, Poldrack RA, and Desmond JE: The role of left prefrontal cortex in language and memory in PNAS. (1998)95(3):906-13. DOI: https://doi.org/10.1073/pnas.95.3.906
Saller R, Meier R, and Brignoli R: The use of Silymarin in the treatment of liver diseases in Drugs. (2001); 61:2035-2063. DOI: https://doi.org/10.2165/00003495-200161140-00003
Teksoy O, Sahinturk V, Cengiz M, İnal B, Ayhancı A: The Protective Effects of Silymarin on Thioacetamide-Induced Liver Damage: Measurement of miR-122, miR-192, and miR-194 Levels. Applied Biochemistry and Biotechnology, 06 Dec 2019, 191(2): 528-539. DOI: https://doi.org/10.1007/s12010-019-03177-w
Cengiz, M: Renoprotective effects of Silybum marianum (L.) Gaertn (Silymarin) on thioacetamide-induced renal injury: Biochemical and histopathological approach. Pakistan Journal of Pharmaceutical Sciences. Sep2018 Supplement Special, p2137-2141.
Muriel P, and Mourelle M: Prevention by silymarin of membrane alterations in acute CCL4 liver damage in J Appl Toxicol. (1990a)10;275–279. DOI: https://doi.org/10.1002/jat.2550100408
Muriel P and Mourelle M. The role of membrane composition in ATPase activities of cirrhotic rat liver: effect of silymarin in J Appl Toxicol. (1990b) 10;281-284. DOI: https://doi.org/10.1002/jat.2550100409
Abdel-Moneim AM, Al-Kahtani MA, El-Kersh MA, and Al-Omair MA. Free radical-scavenging, anti-inflammatory/anti-fibrotic, and hepatoprotective actions of taurine and silymarin against CCl4 induced rat liver damage in PLoS ONE. (2015)10: e0144509. DOI: https://doi.org/10.1371/journal.pone.0144509
Galhardi F, Mesquita K, Monserrat JM, and Barros DM: Effect of Silymarin on biochemical parameters of oxidative stress in aged and young rat brain in Food ChemToxicol. (2009); 47:2655-2660. DOI: https://doi.org/10.1016/j.fct.2009.07.030
Wang MJ, Lin WW, Chen HL, Chang YS, Ou HC, Kuo JS, Hong JSand Jeng KCG: Silymarin protects dopaminergic neurons against lipopolysaccharide‐induced neurotoxicity by inhibiting microglia activation in Eur J Neurosci. (2002) 16:2103-2112. DOI: https://doi.org/10.1046/j.1460-9568.2002.02290.x
Wang C, Wang Z, Zhang X, Zhang X, Dong L, Xing Y, Li Y, Liu Z, Chen L, Qiao H, Wang L, and Zhu C: Protection by silibinin against experimental ischemic stroke: Up‐regulated pAkt, pmTOR, HIF‐1α and Bcl‐2, down‐regulated Bax, NF‐κB expression in Neurosci Lett. (2012) 529:45-50. DOI: https://doi.org/10.1016/j.neulet.2012.08.078
Nencini C, Giorgi G, and Micheli L: Protective effect of silymarin on oxidative stress in rat brain in phytomedicine. (2007) 14:129-135. DOI: https://doi.org/10.1016/j.phymed.2006.02.005
Sathyasaikumar KV, Swapna I, Reddy PV, Murthy CRK, Roy KR, Gupta AD, Senthilkumaran B, and Reddanna P: Co-administration of C-phycocyanin ameliorates thioacetamide-induced hepatic encephalopathy in Wistar rats. J NeurolSci. (2007) 252(1):67-75. DOI: https://doi.org/10.1016/j.jns.2006.10.014
Cengiz M, Ayhanci A, Kutlu HM, Musmul A: Potential therapeutic effects of silymarin and silymarin-loaded solid lipidnanoparticles on experimental kidney damage in BALB/c mice: biochemical and histopathological evaluation. Turk J Biol (2016) 40: 807-814 DOI: https://doi.org/10.3906/biy-1506-75
Mansour, HH, Hafez, HF, Fahmy, NM., Silymarin Modulates Cisplatin-Induced Oxidative Stress and Hepatotoxicity in Rats. Journal of Biochemistry and Molecular Biology, Vol. 39, No. 6, November (2006), pp. 656-661
Bashir S, Sharma Y, Irshad M, Nag TC, Tiwari M, Kabra M, and Dogra TD: Arsenic induced apoptosis in rat liver following repeated 60 days exposure in Toxicology. (2016)217 63-70. DOI: https://doi.org/10.1016/j.tox.2005.08.023
Chen LQ, Wei JS, Lei ZN, Zhang LM, Liu Y, and Sun AY: Induction of Bcl-2 and Bax Was Related to Hyperphosphorylation of Tau and Neuronal Death Induced by Okadaic Acid in Rat Brain inThe Anatomical Record Part A. (2005)287A:1236-1245. DOI: https://doi.org/10.1002/ar.a.20241
Yip KW and Reed JC: Bcl-2 family proteins and cancer in Oncogene (2008)27(50):6398-406. DOI: https://doi.org/10.1038/onc.2008.307
Mohan S, Abdelwahab SI, Kamalidehghan B, Syam S, May KS, Harmal SM, Shafifiyaz N, Hadi AHA, Hashim NM, Rahmani M, Taha MME, Cheah SC, and Zajmi A: Involvement of NF-κB and Bcl2/Bax signaling pathways in the apoptosis of MCF7 cells induced by a xanthone compound Pyrano cycloartobiloxanthone A. Phytomedicine. (2012)19(11):1007-15.  Hector S and Prehn JH: Apoptosis signaling proteins as prognostic biomarkers in colorectal cancer: a review in Biochim Biophys Acta. (2009)1795(2):117-29.
El-Ghazaly MAE, Rashed EF, Shafey GM, Zaki HF, and Attia AS: Amelioration of thioacetamide-induced hepatic encephalopathy in rats by low-dose gamma irradiation in Environ. Sci. Pollut. Res. (2019) 27(1):334-343. DOI: https://doi.org/10.1007/s11356-019-06934-w
Khanna A and Trigun SK: Resveratrol Normalizes Hyperammonemia Induced Pro-Inflammatory and Pro-Apoptotic Conditions in Rat Brain inInt J Complement Alt Med. (2016)4(2):00115. DOI: https://doi.org/10.15406/ijcam.2016.04.00115
Idriss H and Naismith JH: TNF Alpha and the TNF Receptor Superfamily: Structure-Function Relationship(s) Microsc Res Tech. (2000); 50(3):184-95. DOI: https://doi.org/10.1002/1097-0029(20000801)50:3<184::AID-JEMT2>3.0.CO;2-H
Yuan J and Yankner BA: Apoptosis in the nervous system in nature. (2000)407(6805):802-809. DOI: https://doi.org/10.1038/35037739
El-Marasy SA, El Awdan SA, and Abd-Elsalam RM: Protective role of chrysin on thioacetamide-induced hepatic encephalopathy in rats inChem. -Biol. Interact. (2018); 299:111-119. DOI: https://doi.org/10.1016/j.cbi.2018.11.021
Kyrylkova K, Kyryachenko S, Leid M and Kioussi C. Detection of apoptosis by TUNEL assay in Methods Mol Biol. (2012)887:41-7. DOI: https://doi.org/10.1007/978-1-61779-860-3_5
Bustamante J, Lores-Arnaiz S, Tallis S. Rosello DM, Lago N, Lemberg A, Boveris A, and Perazzo JC: Mitochondrial dysfunction as a mediator of hippocampal apoptosis in a model of hepatic encephalopathy in Mohl Cell Biochem. (2011) 354:231-240 DOI: https://doi.org/10.1007/s11010-011-0822-5
Copyright (c) 2020 Ozgun Teksoy, Varol Sahinturk, Mustafa CENGİZ, Behcet İnal, Adnan Ayhancı
This work is licensed under a Creative Commons Attribution 4.0 International License.