Hepatoprotective role of unacylated ghrelin in different doses: an experimental study
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Abstract
OBJECTIVE: To investigate the hepatoprotective effects of Unacylated Ghrelin (UAG) at varying doses in the management of acute liver injury in Wistar albino rats.
METHODS: This quasi-experimental study was conducted at Department of Physiology, Isra University, Hyderabad, Pakistan from March to August 2023. Thirty Wistar albino rats (200-250 grams) were randomly divided into five groups (n=6). Group A served as the control, while liver injury was induced in Groups B, C, D, and E via intraperitoneal injection of 0.1% CCl₄. Groups C, D, and E were subsequently treated with low, medium, and high doses of UAG, respectively. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and superoxide dismutase (SOD) levels were assessed, along with liver histopathology.
RESULTS: Pre-experimental body weights (Mean±SD) for groups A, B, C, D, and E were 227.33±7.75 g, 229.80±2.08 g, 228.70±5.34 g, 231.33±8.69 g, and 236.38±10.63 g, respectively. The liver index was 4.36±0.28, 6.65±0.37, 5.80±0.17, 5.70±0.08, and 5.06±0.23, respectively, across the groups. A statistically significant (p<0.05) decline was observed in group B compared to group C, D and E. Moreover, statistically significant (p<0.05) rise in ALT, AST, Serum IL-6, TNFα, SOD, and MDA levels in group B compared with the remaining groups.
CONCLUSION: UAG effectively protects the liver from CCl₄-induced injury in rats. Higher doses of UAG reduced liver enzyme levels and improved oxidative stress and inflammation markers, indicating its potential as a therapeutic agent for liver damage. Further research is warranted to explore UAG's therapeutic use for liver disorders.
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References
1. Juanola A, Tiwari N, Solé C, Adebayo D, Wong F, Ginès P. Organ dysfunction and failure in liver disease. Liver Int. 2023 May 24. https://doi.org/10.1111/liv.15622
2. Munir F, Khan MKA. Hepatotoxicity Induced by Carbon Tetrachloride in Experimental Model: Hepatotoxicity Induced by Carbon Tetrachloride. Pak BioMed J 2023:10-5.
3. Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, et al. Ghrelin. Mol Metab. 2015 Mar 21;4(6):437-60. https://doi.org/10.1016/j.molmet.2015.03.005
4. Ringuet MT, Furness JB, Furness SGB. G protein‐coupled receptor interactions and modification of signalling involving the ghrelin receptor, GHSR1a. J Neuroendocrinol 2022;34(9):e13077. https://doi.org/10.1111/jne.13077
5. Ezquerro S, Mocha F, Frühbeck G, Guzmán-Ruiz R, Valentí V, Mugueta C, et al. Ghrelin reduces TNF-α–induced human hepatocyte apoptosis, autophagy, and pyroptosis: role in obesity-associated NAFLD. J Clin Endocrinol Metab 2019;104(1):21-37. https://doi.org/10.1210/jc.2018-01171
6. Quiñones M, Fernø J, Al-Massadi O. Ghrelin and liver disease. Rev Endocr Metab Disord 2020;21:45-56. https://doi.org/10.1007/s11154-019-09528-6
7. Lewiński A, Karbownik-Lewińska M, Wieczorek-Szukała K, Stasiak M, Stawerska R. Contribution of ghrelin to the pathogenesis of growth hormone deficiency. Int J Mol Sci 2021;22(16):9066. https://doi.org/10.3390/ijms22169066
8. Hornsby AK, Buntwal L, Carisi MC, Santos VV, Johnston F, Roberts LD, et al. Unacylated-ghrelin impairs hippocampal neurogenesis and memory in mice and is altered in Parkinson’s dementia in humans. Cell Rep Med 2020;1(7). https://doi.org/10.1016/j.xcrm.2020.100120
9. Jabeen A, Ahsin S, Nasar Abbas ZS, Kiyani H. Ghrelin: A Potent Nephro-protective Agent against Nicotine Induced Kidney Damage in Mice. Pak J Med Health Sci 2023;17(01):171. https://doi.org/10.53350/pjmhs2023171171
10. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th edition. Washington (DC): National Academies Press (US); 2011. Accessed on: January 10, 2023. Available from URL: https://www.ncbi.nlm.nih.gov/books/NBK54050/. https://doi.org/10.17226/12910.
11. Gong Y, Qiu B, Zheng H, Li X, Wang Y, Wu M, et al. Unacylated ghrelin attenuates acute liver injury and hyperlipidemia via its anti-inflammatory and anti-oxidative activities. Iran J Basic Med Sci 2024;27(1):49. https://doi.org/10.22038/IJBMS.2023.70831.15388
12. Kiyani HP, Ahsin S, Imran M, Ashraf H. Effect of ghrelin in alleviating nicotine induced oxidative stress in balb/C mice. Pak J Physiol 2022;18(3):3-6. https://doi.org/10.69656/pjp.v18i3.1451
13. Alharbi S. Exogenous administration of unacylated ghrelin attenuates hepatic steatosis in high-fat diet-fed rats by modulating glucose homeostasis, lipogenesis, oxidative stress, and endoplasmic reticulum stress. Biomed Pharmacother 2022;151:113095. https://doi.org/10.1016/j.biopha.2022.113095
14. Au CC, Docanto MM, Zahid H, Raffaelli F-M, Ferrero RL, Furness JB, et al. Des-acyl ghrelin inhibits the capacity of macrophages to stimulate the expression of aromatase in breast adipose stromal cells. The J Steroid Biochem Mol Biol 2017;170:49-53. https://doi.org/10.1016/j.jsbmb.2016.07.005
15. Ugwu FN, Yu AP, Sin TK, Tam BT, Lai CW, Wong S, et al. Protective effect of unacylated ghrelin on compression-induced skeletal muscle injury mediated by SIRT1-signaling. Front Physiol 2017;8:962. https://doi.org/10.3389/fphys.2017.00962
16. Ramos-Tovar E, Muriel P. Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver. Antioxidants 2020;9(12):1279. https://doi.org/10.3390/antiox9121279
17. Rossetti A, Togliatto G, Rolo AP, Teodoro JS, Granata R, Ghigo E, et al. Unacylated ghrelin prevents mitochondrial dysfunction in a model of ischemia/reperfusion liver injury. Cell Death Discov 2017;3(1):1-11. https://doi.org/10.1038/cddiscovery.2017.77
18. Tuero C, Becerril S, Ezquerro S, Neira G, Frühbeck G, Rodríguez A. Molecular and cellular mechanisms underlying the hepatoprotective role of ghrelin against NAFLD progression. J Physiol Biochem 2023;79(4):833-49. https://doi.org/10.1007/s13105-022-00933-1
19. Jing Z-T, Liu W, Xue C-R, Wu S-X, Chen W-N, Lin X-J, et al. AKT activator SC79 protects hepatocytes from TNF-α-mediated apoptosis and alleviates d-Gal/LPS-induced liver injury. Am J Physiol-Gastrointest Liver Physiol 2019;316(3):G387-G96. https://doi.org/10.1152/ajpgi.00350.2018
20. Guo Y, Gao S, Jiang Z, Huang J, He X, Jin R, et al. Calcium-sensing receptor (CaSR) agonist R568 inhibits small intestinal motility of mice through neural and non-neural mechanisms. Food Function 2021;12(23):11926-37. https://doi.org/10.1039/d1fo01988k
21. Raghay K, Akki R, Bensaid D, Errami M. Ghrelin as an anti-inflammatory and protective agent in ischemia/reperfusion injury. Peptides 2020;124:170226. https://doi.org/10.1016/j.peptides.2019.170226
22. Bianchi E, Boekelheide K, Sigman M, Hall SJ, Hwang K. Ghrelin modulates testicular damage in a cryptorchid mouse model. PLoS One 2017;12(5):e0177995. https://doi.org/10.1371/journal.pone.0177995